The Human Journey, Volume I, Chapters MNBackmatter

7/30/2019 The Human Journey, Volume I, Chapters MNBackmatter

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Chapter M. Steps 91-100

Closing in on a Major Transition

Step 91. Biochemical coordination and control within a TT.

Ultimately, the nucleic-acid foundation of a bion coordinates its biochemical interactions. InKingdom 1 (bioids) and some bions in Kingdom 2 (ssBRNA), this may be done, if at all, by ribozymes. But

starting with other bions in Kingdom 2 and continuing throughout all the rest of biology, it is done

mainly by genes, whether in RNA or later in DNA. These genes determine a bions potential,what it can

do. But what determines its behavior or what it actually does?

A gene may be active or on (1) at all times, doing what it does whenever it can, to the extent that

it can. (2) If it does not need to be on all the time, then it may be set up to be on except when it is

specifically turned off (to be inactive), or, if it is needed more rarely, (3) it may be set up to be off

(inactive) except when it is turned on. (4) Many genes can be turned either on or off ascircumstances

demand.

To turn genes on or off requires separate sections of the genetic material, RNA in some

protobions and DNA in more sophisticated bions, and normally a sensor to report the chemicalcondition which gives rise to the need to change the setting. The sensor recognizes the chemical signal

(which may be a molecule in the environment usually Oceanic or within the bion, or a lack or

shortage of some molecule in the bion or in the environment). This sensor then acts on the setting to

cause it to be set as it needs to be.

The sections of the genome that provide the settings are usually specific for each gene,

although, more rarely, a single setting may affect a few different genes that do related things. The

settings are usually called either promoters (if they turn on a particular gene) or suppressors (if they

turn it off). Changing the setting may consist of creating a new molecule that goes to the site of the

gene and blocks it or activates it or destroys a molecule that has been blocking the gene, depending on

the particular gene and situation. It is also possible, though not common in normal bions, for RNA to be

created to interfere with the messenger RNA that is effectuating a genes instructions.

This is the general system, though it is really much more complicated than suggested here.

Further, early protobions did not build very complicated systems, so they did not at first need such

extensive control systems. Just how far they got by the time and in the case the of the TTs is not

entirely clear, but certainly they had come some way, having many capabilities, which could not all be

well applied at one time. After all, by the period to which we now look, the total number of enzymes

that could be made by one TT may have exceeded 600 and that might well be too much at any one

moment.

Particularly once started metabolism is a complex, interwoven system of separate series of

sequential chemical interactions, some operating in the opposite direction from others. Assembling

large storage molecules or smaller, simple sugars and amino acids (synthesis or anabolism) could not

usefully be done while at the same time disassembling (catabolism) the same molecules in the same

pathways. Such opposite-direction operations would be wasteful, futile, and self-defeating. As a result,some regular systems of coordination were worked out over the generations through several special

control mechanisms.

The genome could stop making some molecules, like the enzymes so important in moving

chemical changes on a large scale, at a practical speed, and in the right direction. The sensor system

mentioned above can and often does apply feedback to this problem. A sensor may monitor the

amount of some molecular product in a pathway, say, the ultimate output, such as glucose. If the

amount of glucose rises above a certain level, then the sensor-reactor system causes the promoter to


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discontinue its action and the suppressor to turn off the gene and hence the production of an enzyme

needed early in the process. But that method is often too slow, so two other major systems arose for

control ofmetabolism (anabolism plus catabolism) in a more prompt and precise way.

Once enzymes are made, they may persist for a time. They not only can assist in making a

chemical process progress efficiently but sometimes they can influence its direction. That is useful to

prevent pathways from running the wrong way. Yet some process pathways need to be able to run in

either direction at different times. Sugar molecules need to be built and bound to each other for

storage in times of plenty but also broken down for energy or spare parts in more difficult times.

So there need to be ways to reverse the direction of flow. One way is to have reversible steps

but different enzymes for some of those steps, where those critical enzymes work more efficiently in

one direction, or, more often, where at least some of the enzymes for processing in one direction are

temporarily replaced by different enzymes which take a slightly different route (through one or more

steps around a crucial point in the process to avoid the step that is more efficient in the wrong direction

for the current need).

In addition, a second way to prevent pathways from running the wrong way (for current need)

has evolved. That is for some of the steps or chemical changes not to be reversible, usually because

those irreversible steps would be too energy costly to be managed in the wrong direction. When it

becomes necessary to go in the opposite direction, that step is skipped and an alternate route takenback to the pathway, sometimes adding two or three steps to get past the energy barrier by a few steps

taking less energy. Usually both the presence of some irreversible steps and different enzymes and

routes in a pathway of sequential steps are combined.

The easiest, and therefore the most common, way to evolve two processes in the opposite

direction, one to build up a particular molecule and the other to break it down, is for most of the steps

to be the same in both directions. One reason that is easy, besides skipping the creation of an alternate

step, is that most chemical processes are inherently reversible. To control direction, then, mostly does

not involve using different interactions, but some of the steps must go in one direction only. If these are

not too far apart, they prevent the process from running in the wrong direction for the occasion.

Suppose the bion needs to build something, say, a sugar molecule or a polymer for sugar

storage. This building process is called synthesis in any particular case and is also an example ofanabolism, a word usually used for all the syntheses going on in a bion. During that building process it

would be counterproductive for the process to run partway and then reverse. If an irreversible step is

part of the path, then that step, once accomplished, cannot be directly reversed, so no steps before that

can be reversed.

In that way, the irreversible steps act like valves to limit processes that would proceed in the

wrong direction. That much is like the way that animals veins work. Nothing pumps venous blood, but

valves prevent it from running backward. Typically, in otherwise reversible, biochemical processes, an

irreversible step must occur after every few reversible steps. The valve effects keep the system from

retreating very far and thus move the process along. Also the direction of results in a chemical

interaction depends heavily on the concentration of the ingredients or reactants put in, the products

needed from earlier steps, and the amount or concentration of the product of the current step still

present.

While the resulting molecules are too few, the process will continue forward. When they

become sufficient, the process may stop or even go backward. By preventing some steps from going

backward automatically, those steps go only one way, and not only prevent retreat but also keep

reducing the product of the previous step, thus pulling that step forward likewise. When product E of

step 5 is changed to product F by step 6, which cannot convert back, that product F is effectively gone

(concentration is zero), so more E is made into F. For both reasons the process works. The numbers of

steps that need to be irreversible and the numbers that are reversible do not have a known, particular


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ratio. But, for example, typically three irreversible steps, if spaced properly, suffice for a path of eight to

twelve steps.

Besides eliminating necessary enzymes to stop a process, a way to control the rate of enzyme

action and thus of a process is to alter the amount of production of enzyme. Yet this is not the only way.

Instead of, or in addition to, altering the amount of enzyme produced, an enzyme may be inactivated

after it is made or reactivated for awhile after inactivation. This may be done faster than by simply

waiting for the protein enzymes to break up spontaneously or be dismantled. For example, adding

phosphate groups to an enzyme, or deleting one, in some cases, will inactivate the enzyme, so it does

not act further even though it still exists for a time. This method of controlling the speed of action of a

particular enzyme probably arose much earlier than the next, and probably was used by the TTs.

Another way to control the rate of enzyme action is to modify the speed at which a particular

enzyme works. This is a more precise and sophisticated mode of control than discontinuing production

of the enzyme or totally inactivating it by chemical changes, but it took longer to develop. It may have

been begun by a TT but was probably not developed very far in their time. Today it is the most common

method of control. It consists of the evolution of enzymes with more than one active site.

It will be remembered that an enzyme is a protein molecule whose sequence of amino acids

causes it to fold into a particular three-dimensional shape. That shape enables the enzyme to fit the

molecule on which it is adapted to act, sometimes more than one other molecule, and to bring its activesite into contact or close proximity to the crucial part of that molecule, its substrate.

The active site is the part of the enzyme that influences the substrate, that is, catalyzes it, and

usually consists of very few amino acids. Now, this new system of control is built into some special

enzymes called allosteric enzymes. What makes them different is that they have more than one active

site. These active sites on the same enzyme may each be able to catalyze the needed interaction of a

different molecule of the substrate. This possibility is useful because the limiting factor in real world

biochemical reactions is usually the level of enzyme activity.

In addition, some small molecules may be produced in limited amounts according to

circumstances. These special, small molecules can also fit into the same binding sites mentioned just

above, or at a nearby location which alters the shape of that part of an enzyme molecule so as to

inactivate a particular substrate binding site. Thus, if none of the small molecules is produced or in thevicinity, then an allosteric enzyme with, say, three active sites will be able to act on three substrate

molecules at a time, acting effectively like three enzyme molecules, giving that enzyme maximum

potential productivity.

If using all three active sites to react with substrate molecules makes the catalytic activity too

fast, then the bion can release a limited number of the small molecules mentioned in the preceding

paragraph, say, as many as the enzyme molecules on the particular job. On average, then, these

molecules will inactivate a third of the active sites on the enzymes, thus reducing enzymatic activity

accordingly. Producing the small molecules is much faster and less costly in terms of energy than

changing the number of enzymes.

Similarly, if production is too fact, as many small molecules again can be released (produced),

thus filling a third more of the active sites (in some cases occupying all three of the active sites on some

enzymes, only two on others, only one on still others, and perhaps none on a few). Thus, total

production will be reduced further. In the same way, a further reduction could be obtained with still

more of the small molecules (particular ones for each type of enzyme).

This system permits rapid and inexpensive fine tuning of the amount of production in a

particular pathway, allowing three different rates of individual enzyme activity, besides the basic on and

off five graded levels. The allosteric enzymes for a particular kind of interaction, of course, may have

more or fewer binding sites than this example. The point is that such a system permits a prompt degree


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of different precise levels ofbinding affinity, such as this example of three-state binding affinity, which

can be quite a valuable means of control. Enzymes of this type are also calledregulatory enzymes.

This method is the most prevalent today but was probably less fully developed in the time of the

TTs. Of course, the details differ in each of the hundreds of chemical interactions in TTs, the thousands

in many cellular bions, and the tens of thousands in more complex bions like us. Even the details

consistent from one biological subsystem to another are very numerous but this is not the place to

pursue them further.

Step 92. More on saccharides: pentose phosphate paths.

a. Getting here.From the use of simple sugars as sources of spare parts for amino acid repair and replacement

through their synthesis, polymerization into storage polysaccharides like glycogen and structures like a

bion-surrounding wall to their partial destruction through glycolysis for the sake of extracting chemical

energy in the form of nucleotide triphosphates, and the regulation of the whole process in step 91, we

have emphasized the late role of sugars in biology as the third great category of biological molecules

after nucleic acids and proteins, through the last few steps of chapter K, throughout chapter L, and atthe start of this chapter.

Now, in a sense, we return to their first role in biology, in the form of the ribose so basic and

crucial in the formation of the first nucleotides that assembled themselves into the first bions. That

ribose on which RNA is in part founded, and the deoxyribose of DNA, are among the pentoses named in

the title of this step.

b. Functions of pentose phosphate paths.Here we examine briefly a few related paths involving pentose (five-carbon) sugars, including

making them from hexose (six-carbon) sugars such as glucose. These pathways, at least as they seem to

have started out, did not primarily have the function of getting chemical energy in the form ofnucleotide triphosphates, as glycolysis did. Rather, these pathways seem to have arisen in building

three rather different and specialized functions:

(1) Changing six-carbon glucose (which by the this time TTs were storing as glycogen or somethingvery like it) into ribose-phosphate for use in synthesis of individual nucleotides and the

polynucleotide nucleic acids, especially in periods of rapid reproduction or nucleotide repair;

(2) Changing one kind of simple sugar into another, according to current need; and(3) Assembling a supply of the co-enzyme NADPH.c. Main phases of the process.

Numerous different paths, with various relationships to each other, fall into the category of

pentose-phosphate pathways, but most fall into two main phases. In the first phase, the now

convenient and well controlled, simple sugar, glucose, is converted, in four steps, into ribose-5-

phosphate, the founding stone of biology and (potentially) of nucleotides and nucleic acids.

These first four steps are assisted (catalyzed) by two different dehydrogenase enzymes. These

enzymes encourage their substrates (starting with glucose) to give up hydrogen atoms. NADP+

accepts

these two hydrogen atoms, becoming NADPH2. In addition, at one step, one of the intermediate

products of the path takes in the equivalent of a molecule of water from the surrounding Ocean (by now


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a sort of partitioned off, private bit of Ocean), and one of the original six carbons of glucose is lost in a

molecule of carbon dioxide (see diagram below).

The oxidative phase of the pentose phosphate path: (1) depicts the beginning of the first phase with glucose -6-

phosphate; this is catalyzed by NADP+

(which becomes NADPH2 in the process); (2) the first product then reacts

with water (H2O), giving up a hydrogen ion; (3) the second product, ribulose-5-phosphate, again, is catalyzed by

NADP+

(which becomes NADPH2 in the process, as before); (4) with the final result, ribose-5-phosphate and a

molecule of carbon dioxide (CO2) (from Wikimedia Commons, article pentose phosphate pathway).

The second phase of this pathway may or may not be needed. We learned previously that two

rather similar kinds of molecules, ketones and aldehydes, may become sugars. At an intermediatestage, above, depending on what the bion needs at the moment, two different enzymes may convert a

ketone into an aldehyde or an aldehyde into a ketone by exchanging their non-common side groups. If

it needs more ribose or other pentose, that is the product made. If, instead, it needs more NADH2, that

is what it gets. If exact balance is needed, the second phase does not have to occur and does not.

Specifically, the part of a molecule removed from one potential sugar and moved to another

consists of two particular carbon atoms (a similar process occurs in other pathways). Thus, the two

enzymes, transketolase and transaldolase, transfer carbon atoms, two at a time, to another molecule,

and hence build whatever sugar is needed within the range of adding or subtracting two carbons. But

this is a wide range because, if the NADH2 is needed rather than the pentose, the pentose may be

changed back into glucose and split into what ends being glyceraldehyde-3-phosphate, dispensing with

the pentose but still yielding the NADH2 in even larger quantity. (Remember glyceraldehydes, three-carbon potential sugars.)

(Side note: a genetic defect that prevents red blood cells from making the first enzyme for the

pentose phosphate path can produce anemia if a certain anti-malarial drug is taken because NADPH is

vital to keep hemoglobin working properly.)

d. Effect.At first glance, an alternative way to get or process a simple sugar molecule may seem to be a

trivial detail in an already complex system. But consider:

(1) Throughout much of the history ofprotobions before they became TTs, they depended onOcean water movements to bring directly to themselves, or bring themselves to, the component

molecules, the energy sources such as phosphates and especially nucleotides with triple

phosphate bonds, the metal catalysts, and other necessities for survival and reproduction (or

survival long enough to reproduce);

(2) As they moved into the category of Third Transitionists (TTs), a few of those protobions beganto develop the ability to build numerous needed molecules, such as amino acids, heterocyclic

organic bases, sugars, and polysaccharide storage molecules and surrounding walls for

themselves even building up ready energy in the form of nucleotide triphosphates and reserve


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energy in the form of sugar without merely waiting for the necessary items to show up by

chance. But their limited supply and use of energy until recently had probably limited their

numbers and food needs. Now, recently, their new projects had provided more energy and

food, so they could proceed to increase their numbers, except for one thing;

(3) They had not been easily able to build their own ribose molecules, despite having the ability todo everything else for reproduction, but now,

(4) At least one of the TTs could build its own, and itsown descendants, ribose. That achievementremoved the last obstacle to rapidly increasing reproduction and hence numbers of TTs, at least

in that lineage. Their numbers rapidly grew so large that rocks formed thereafter (about 3.9

billion years ago) have had signs of biological chemistry in them ever since! Biology quickly

became much more important on Earth, even if still largely confined to the vicinity of the ridges

at the bottom of the Ocean.

(5) Another effect seemingly a side effect during the development of that system before its finalrefinement was that a considerable amount of excess NADH2 began to collect, with telling

consequences, as we shall shortly see.

Step 92. Some specialized molecules ready to work together.

a. Co-enzyme A.We have previously met co-enzyme A as one of a group of so-called co-enzymes, meaning that

they work along with enzymes. They are not technically enzymes for two reasons: first, because do not

mainly function as catalysts, but as an acceptor, carrier, and donor of electrons, or some atom or

functional group of atoms, such as hydrogen, a methyl group, an amine group, etc.; and second, because

a catalyst normally comes out of a chemical interaction unchanged from its state before the interaction,

even if it is temporarily altered during part of the interaction. Co-enzymes often are changed by an

interaction, having more or less of the item being accepted, carried, or donated, when the interaction

ends, than before it started. They depend on being restored by a later, different interaction. As we

have seen, NAD, NADP, and FAD accept hydrogen atoms in a reaction where the important moleculebeing worked on needs to lose such atoms, but they are primarily electron acceptors, carriers, and

donors. They carry whatever they have accepted (and so are altered from their former state by having

that extra item, and later donate it to some other molecule) in a different interaction, thus being

restored to their original state.

b. Co-enzyme A continued.Co-enzyme A, like them, accepts, carries, and donates, but not the same thing. What it accepts,

carries, and donates are small organic molecular parts, i.e., pieces of carbon chains and whatever may

be bound to them. In particular, it tends to accept acetylgroups from pyruvic acid, the product of

glycolysis. It can also add carbon dioxide (CO2) from a bicarbonate ion (HCO3-) or comparable source to

an acetalgroup which it already carries. Thus, at the end of glycolysis, a co-enzyme A is left, carrying the

acetal group until another interaction occurs. That combination of acetal group and co-enzyme A

remains available (in meaningful supply) for an appropriate interaction and we shall meet an important,

new occasion for it in the next step.

The acceptance of the acetal group makes the combination known as acetyl-co-enzyme A

(acetyl-CoA) and occurs under the influence of biotin (a vitamin) and an enzyme specific to that function

(acetal-CoA carboxylase) and with the assistance of a nucleotide triphosphate (ATP). The interaction


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uses the energy of one of the phosphate bonds (in severing that bond, leaving the nucleotide with one

less phosphate) and creates the three-carbon malonic-acid molecule, then still carried by co-enzyme A.

Acetyl groups consist of two carbon atoms bound together. Normally the carbon atom closest

to the co-enzyme A is also doubly bound to an oxygen atom, leaving its one remaining available bond for

attaching to the sulfur atom at the active site of co-enzyme A. The other carbon atom, besides being

singly bound to the first carbon just mentioned, is also bound to three hydrogen atoms. As mentioned

before, sulfur has two potential bonds, like oxygen, and can form a so-called thiol group with oxygen,

just like the hydroxyl group (OH), making anSH group.

When co-enzyme A accepts an acetyl group, it loses its end hydrogen atom. In place of the

hydrogen, the sulfur group singly binds to the acetyl group. When it is carrying such an acetyl group, co-

enzyme A is called acetyl-co-enzyme A (acetyl-CoA). Because it is such a complex molecule, almost the

same abbreviation is also used for it in structural formulas, but in the latter case the thiol group is added

to show the bond of acceptance and carrying. Acetyl-co-enzyme A and malonyl-transfer co-enzyme A

may be shown as follows:

H O H O

| || | ||

H C C S CoA OOC C C S CoA| |

H H

Acetyl-co-enzyme A Malonyl-transfer co-enzyme A

Acetyl-co-enzyme A: active part on left and extra phosphate at lower right (from Wikimedia Commons).

This co-enzyme, besides our original meeting with it in an introduction to several co-enzymes,

also played a part in what was then a new process and pathway, not previously used by any bion. In

that process, acetyl-CoA molecules delivered and donated an acetyl group and seven malonyl-CoA

molecules previously acquired, initially from glycolysis.

First, we shall consider its structure. Like some other major co-enzymes, it contains two major

parts: (1) a nucleotide (adenine), including its double-ring organic base, its ribose, and the usual

phosphate group of a nucleotide, bound to (2) a second phosphate group, which is, in turn, bound to an

intermediatepantothenate (pantothenic acid, a vitamin). The pantothenic acid, in its turn, is bound toanother small (but crucial) additional section, at the end of which is the active thiol group.

In general, then, acetyl-CoA is structured, like some other co-enzymes, in having two main parts

bound together by two phosphate groups which hold the whole molecule together. Also, like the

others, one of those main parts is composed of three sub-parts, the phosphate, the middle piece, and

the end piece. That is why some are calleddinucleotides. In those, the end piece other than the usual

nucleotide at least has a nucleotide-like ring. This is not so in the case of acetyl-CoA. The middle part

here on the non-nucleotide side is pantothenate and the end part is a brief chain.


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Pantothenic acid, which forms part of acetyl-CoA (from Wikimedia Commons).

A third phosphate group appears at the side of the acetyl-CoA molecule, bound to the ribose,

but outside the chain, besides everything mentioned in the paragraph. The reader can see why the

molecule is customarily abbreviated, even in structural formulae. We shall not deal with the full

molecular detail further. It is helpful, though, to recognize that the word acetyl- in the name of the

molecule refers to the two extra carbon atoms mentioned above. Also, note the sulfur atom (S) near

the left end of the structural formula, making the thiol group with the end hydrogen and acting much

like a hydroxyl (OH) group. When the end hydrogen is replaced by other atoms or molecules, the

resulting molecule is still larger.

We should remember both that glycolysis produced many of the acetyl groups in acetyl-CoA

carrier (and potential donor) form and so provided a large, ready supply of them. That supply became

important the next step, as we shall see.

c. ACPAnother related molecule also plays an important role in carrying acyl groups, even in the same

new and important pathway to which we shall shortly be introduced. Unlike what we call co-enzyme A,

which is a separate molecule, a structure exactly like it (basically the same thing) also exists

incorporated into a protein. It is called an acyl-carrier protein (ACP). Not surprisingly, it does essentially

what co-enzyme A does.

d. NADPAs we have already seen, nicotinamide dinucleotide phosphate (NADP) acquires and loses

hydrogen atoms in its chemical interactions. It is primarily an electron acceptor, carrier, and donor. It,

too, plays a major role in the new pathway to be introduced in the next step, enlarging the range of

major (large-volume) biological molecules from three (nucleic acid, protein, and saccharides) to four and

bringing our TTs a new resource that could enable them (or at least one of them) to pioneer the second

empire of bions.

Step 94. A lipid.

a. BackgroundIn the last few chapters, we have seen a small offshoot of the dsDNA, Kingdom-6 protobions,

which I have termed TTs, evolve capabilities beyond those of earlier protobions, developing abilities to

repair, revise, and build a new nucleotides, amino acids, and other amines, using parts of these

molecules and then of simple sugars. They then evolved further ways to use sugars, including creation

of storage polysaccharides like glycogen to build walls of some other polysaccharides, to enclose

themselves in these walls, to break up the storage particles back into simple sugars, to break up sugars


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to collect potential chemical energy in the form of recharged nucleotide triphosphates, and naturally to

connect the chemical pathways for all these capabilities into one large system network.

(This last pathway-connection characteristic was not so much a separate accomplishment,

separately evolved or planned, as it was the natural result of how the use of a favorable mutation

necessarily connects with some existing pathway. Only thus can the mutation be used to help the bion

survive or reproduce. If it does not, the mutation is useless and will be eroded by more useful changes,

if it is to survive or reproduce. That is the only way a new path of biochemical changes can become

established, hence it is connected from the start. It may, however, be refined in some ways over time.

The collection of these processing paths by this point definitely constituted metabolism, the system of

collecting, using, storing, building (synthesis or anabolism), and breaking down molecules, both sugar

and amino acids, to get chemical energy (catabolism). These processes, taken together, constitute

metabolism, listed by some authors as a necessary or defining characteristic of biology. We have seen

that they do not constitute such a limitation or distinction but they have been present in biology since

the time of the TTs.)

b. Latest new functions and their end products.Among the later new functions so evolved in or from the achievements listed in the first

paragraph of this step were glycolysis, pentose-phosphate paths, and a significant rise in the rate of

saccharide use and processing, a resultant rise in the pace and scope of biology, and a rise in

reproduction rates among the TTs.

Glycolysis (of simple, six-carbon sugars, including glucose) used these simple sugars to rebuild

ATP and similar forms of stored potential chemical energy, but also created three-carbon molecules

such as pyruvate, malonate (malonic acid) and, indirectly, triglycerol. In the process, glycolysis also led

co-enzyme A molecules to bind their sulfur atoms to quantities of acetyl groups derived from the

pyruvate and reduced NAD to NADH (the equivalent of adding a valence electron).

The pentose-phosphate pathway increased the amount of ribose phosphate, thus increasing

reproduction, at the same time likewise adding hydrogen atoms to NADP, reducing it as well. These

growing supplies of all these product molecules and effects on co-enzymes from these (then recentlydeveloped) processes naturally tended toward further interactions which would draw off these newly

more numerous molecules and valence electrons. The synthesis of glucose and polysaccharides had

also, by this time, built large supplies, so here too may have been a resource passing the time and scope

for its further growth in this form.

c. Other new classes of molecules or parts of molecules.Besides the three types of biologic molecules then existing in the largest numbers (nucleotides,

proteins, and saccharides), the enclosing walls and new processes also gave the TTs more control over

energy sources (both nucleotide triphosphates for immediate use and saccharides for later use). We

have seen that bions also evolved a considerable number of special-category molecules, such as

porphyrins, co-enzymes, and, by this time, at least a few vitamins. Vitamins are molecules, or parts of

molecules, with special functions necessary to certain processes. They tend to be moderately sized

molecules, as are large amino acids, porphyrins, and nucleotides carrying extra phosphates, but do not

resemble these. Some seem to have catalytic functions although they are not as large as proteins.

Some are incorporated into other molecules, such as proteins (where they constitute an active site) or a

co-enzyme. One vitamin in existence at that early time waspantothenate, the pantotheine part of co-

enzyme A. Another vitamin existing then was biotin.


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d. A use of some of the end products of the TT-developed, new processing pathways.Apart from a large supply perhaps an excess of all these new products, I am not certain why

this next step happened. But, in chemistry, an abundance (or relative concentration within the bions

polysaccharide wall) of something tends to encourage interactions using it. Where the condition

becomes true of several pertinent factors in the same period, a process using several of them seems

highly likely. At any rate, it seems to have occurred, about in the order in which we have proceeded.

(1) This new processing pathway started with an acetyl-CoA molecule, carrying, as its name implies,an acetyl group bound to the co-enzymes sulfur atom. Whether or not this was true at the

beginning, at some point an enzyme (let us call it fatty acid synthase, or FAS) with a cysteine

amino acid in its chain appeared on the scene. The enzyme may also have contained a

pantotheine-phosphate molecule, or later, after further changes, acquired one, rather than

depending on one to appear accidentally, as may have been the case for a while. (TTs and

prokaryotes used seven different enzymes but this pathway is shown here for simplicity because

it the one humans use.)

Recall that cysteine is an amino acid with a sulfur atom in its side chain, useful in

enzymes to link to other amino acids in the same chain (which also have such side sulfurs), to setand hold the three-dimensional shape. But sulfur is also the atom of CoA that holds its short-

carbon-chain temporary burden. That is significant. Recall, too, both that pantotheine is a part

of CoA and that it has attached to itself a phosphate group (see figure in step 93). I infer from

these facts and some others not yet mentioned that, at one time, or in at least one situation,

pantotheine, perhaps only with a phosphate group bound to it, has or had some attraction for

the same acyl groups that CoA now accepts, carries, and donates. Evidently this attraction is

enhanced in FAS. The result was that the FAS enzyme accepted the acetyl group from acetyl-

CoA. (See the figure below, at the end of the pathway description.)

(2) In the next step of this pathway (which we may name after the persistent enzyme FAS), theacetyl group moves spontaneously from the pantotheine part of FAS back to a sulfur atom on its

cysteine part. Step (1) occurs only once in the pathway. Step (2) may happen from six to tentimes in a cycle, depending on the size of the end molecule. The same is true of all the other

numbered steps, because several steps make a cycle. Each cycle adds two carbon atoms (an

acetyl group) to a growing molecule. Each cycle is repeated until the goal size is reached, thus

ordinarily yielding a carbon chain of even numbers of carbon atoms from 14 to 22. In each

cycle, the FAS enzyme remains throughout the FAS pathway. (Oxygen and hydrogen atoms are

also linked to the carbon atoms, as shown in interactions (1) and (2). Later, the oxygen atoms

may all (but one) be replaced by hydrogen atoms, making a saturated molecule, or some may,

making an unsaturated molecule.)

(3) Meanwhile, somewhere else, an often different CoA molecule at possibly a different time picksup another acetyl group from glycolysis, falls under the influence of (a) an enzyme called acetyl

CoA carboxylase, (b) the vitamin biotin, and (c) a triphosphate nucleotide (ATP) to add a

carboxyl group (derived from a bicarbonate ion) to the acetyl group carried by that acetyl-CoA.


11/49

Saturated fatty acid synthesis (from Wikimedia Commons).

(4) Next, this malonyl-Co-A transfers its malonyl to the pantotheine part of the FAS enzyme, closeenough to interact with the acetyl.

(5) In step (5), the carbon dioxide, added to an acetyl in step (3), is lost again, reducing the moleculeback to an acetyl group, but, more importantly, providing the linked energy from loss of that

bond to provide the linked energy for a new bond, hooking the new acetal (still bound to the

pantotheine) to the original acetyl group from cysteine. Hence, FAS now holds a four-carbonacyl group.

(6) The co-enzyme NADPH+H+ (also written NADPH2) next reduces (adds electrons and, in this case,hydrogen atoms, to) FAS. The writing of the FAS enzyme and the four-carbon acyl group it now

carries remain the same.

(7) Now, the hydrogen (H) and hydroxyl (OH) bound to that third carbon atom join each other andelope as a new water molecule (HOH). The second and third carbons therefore double bond to

each other and divide up or share the two hydrogen atoms that had been on the second carbon.

This loss of a water molecule is called dehydration.

(8) Again, NADPH2 reduces the carried four-carbon acyl group, adding two more hydrogen atoms sothat, again, as at the end of interaction (1), all carbon-atom bonds are fully saturated with

hydrogen atoms except the first one. The first cycle has ended. The acyl group is also againbound to the pantotheine part of the FAS enzyme, as at the end of interaction (1).

The whole cycle then runs all over again, except for step (1), with the same series: (2) the now four-

carbon acyl transfers from the FAS pantotheine to its cysteine; step (3) occurs away from the cyclic

process; (4) a CoA donates another malonyl group to the FAS pantotheine; (5) the original four-carbon

acyl group links to the new acyl group, discarding the carboxyl group as carbon dioxide; (6) NADPH2


12/49

adds two hydrogen atoms to the now six-carbon acyl group; (7) a water molecules leaves (dehydration);

and (8) NADPH2 again adds two hydrogen atoms to the acyl group.

These cycles are continually repeated in the synthesis of each individual molecule, adding two

more carbons in each cycle until the molecule is complete. The result is afatty acid, an example of a

lipid. Today, bions use a considerable range of lipids for a number of functions. What the TTs used

them for, or which precise ones they made, is not fully clear. We humans generally makepalmitate, a

16-carbon chain, and use fatty acids as a long-term, emergency source of chemical energy. The most

energy can be obtained from the most reduced fatty acids, meaning those with every spare bond taken

up by a hydrogen atom. Such are saturated acids.

Lipids may be used for connective tissue now, for energy, and for a few other functions. Some

vitamins and other molecules are best dissolved in oils, which are short-chain lipids. We shall meet, in

this chapter but not in this step, a different and crucial value and use of lipids. Fatty acids are a much

more concentrated source of chemical energy than any saccharides, so they take up much less space.

That may be the first use of these lipids by TTs, but that is not certain.

Step 95. Fatty-acid-chain molecules completed and released.

Some clarification of the process set forth in step 94 is appropriate.a. The new pathway described in step 94 illustrates, in more detail than most of the steps

described here, the important principles:

(1) that biological synthesis (building larger molecules from smaller ones) uses, and hence

requires, chemical energy, while catalysis (breakdown of larger molecules into smaller ones) provides

such energy;

(2) that such synthesis also requires reduction (receiving hydrogen or other positively charged

atoms or functional groups and valence electrons), while catalysis typically involves oxidation (loss by

the shrinking molecule of valence electrons and bonds);

(3) that the reducing air of early Earth (and hence slightly acidic Ocean) provided a significant

help in getting biology started and in advancing it rapidly during the period covered in this volume, i.e.,

the first 650 million years after Earths crust hardened. (Todays oxidative air and more alkaline technically basic Ocean would be less favorable for new bions that might try to restart in case of some

planetary disaster); and

(4) that most pathways that have useful reverse directions usually evolve both directions in the

same period, step by step, since most individual interaction-steps in a chemical pathway are

automatically reversible until means of control over them evolves.

b. The pathway described in step 94 does not exactly coincide with the way the TTs originally

developed it. As in some other cases, the path first arose by evolving separate enzymes for each

interaction required. The reader may have noticed that some of these interaction-process steps did not

require enzymes, but were spontaneous responses to previous steps. The prokaryotes, when they

arose, followed this original approach. But in this pathway, as in a number of others, what originally

arose as distinct enzymes later evolved into a single combination (here, the fatty acid synthase) of

enzymes incorporated into a single molecule or complex. (Synthase is a general term for an enzyme that

assists in synthesis; the suffixase is used for most enzymes of any kind.) (For simplicity, rather than

trying to present the multiple enzymes used by prokaryotes, step 94 simply describes the process

pathway as it is in animals. But in our intestines lives a prokaryote, Escherichia coli, which still uses the

old system.)

c. The pathway in step 94 was, of course, the synthesis of fatty acids. It was mentioned that

maximum energy should be attainable from a saturated molecule, i.e., one with a hydrogen atom

involved in every bond except the one between each two carbon atoms in order. Even so, fatty acids


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are not usable in our bodies for making certain kinds of needed lipids; hence, saturated fat is unhealthy

even though it can provide energy. Thus we need unsaturated fatty acids. A double bond between two

successive carbon atoms in a fatty acid chain makes it unsaturated at that point. The term

polyunsaturated means, in effect, more than one such double bond in each such molecule. Nutritionists

advise us that our fats should be polyunsaturated.

d. We have seen the process of building a fatty acid molecule. When the molecule is complete,

however long it needs to be, it is released from the FAS molecule in animals and from the last enzyme to

which it was linked in the original TT pathway, in an interaction in which a water molecule or its

equivalent is taken up. The hydrogen ion of the water molecule is taken by enzyme, and the hydroxyl (-

OH) ion is taken by the origin first carbon of the chain, which still has its original double-bonded oxygen

atom. Hence, with both the double-bound oxygen at (and the oxygen or hydroxyl of the water molecule

now attached to) the end carbon, that much of the chain becomes a carboxyl group, effectively making

the chain an organic acid, as the term fatty acid implies. The molecule is complete but it has further to

go.

Step 96. Glycerol (triaglycerol and triglycerides).

As might be expected, when glycolysis splits six-carbon sugar molecules into three-carbon sugarmolecules, although the product is pyruvate, other processes can make it back into a sort of three-

carbon sugar with a hydroxyl group on each carbon, but this also makes it into an alcohol. Alcohols and

acids interact with each other, making molecules of water and joining the rest of each original molecule

pair into an ester. An ester built from a three-carbon base and three hydroxyl groups is calledglycerol.

It forms esters.

Fatty acids are stored in the form of such esters, consisting of the glycerol (a simple proto-sugar)

acting as an alcohol and three molecules of one kind of fatty acid (any kind, but all three must be of the

same kind), each fatty acid joined at the carboxyl end to the glycerol at each hydroxyl group. A new

ester link is formed from each of the interactions, one for each glycerol-carbon-to-fatty-acid link, making

three in all. In each case, the end hydrogen of the carboxyl group joins the hydroxyl group os the

glycerol ( 3H2O) and the remainder of the four molecules (three former fatty acid molecules and theglycerol) join as one ester.

To accomplish this, however, some other things must happen. A CoA molecule must take up

each fatty acid chain (making the combination again an acyl-CoA as in the building of the chain in the

first place). An enzyme (an acyl transferase), a phosphate group, and a phosphatase (enzyme) also play

a part. The resulting new fat storage molecule, a glycerol based storage lipid, is as shown below. In this

form, such molecules tend to collect together in water (making a simple droplet of mostly fat within the

bions space, which is, in turn, enclosed by the polysaccharide wall).

Triacylglycerol, a triglyceride (from Wikimedia Commons).


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Step 97. Glycerophospholipids.

We do not yet have enough information to say whether the first interactions of fatty acid

metabolic paths occurred (1) spontaneously, (2) functioned to reestablish and maintain energy and co-

enzyme carrier balance, (3) functioned as energy storage and sources from the beginning, or (4)

provided some other function. But, as suggested above, these first interactions almost surely did evolve

synthetic and catabolic directions in those paths during the same period, the starting direction probably

depending on chance, circumstance, and environment, as well as chemical properties. In a general way,

that original TT discovery has been characteristic of most cellular biology ever since, although details

vary in different biota.

Of course, phosphate ions continued to be common and to participate constantly in a wide

range of biochemical interactions within the enclosed bit of Ocean within the bions wall. They even

played a part in the last chemical interaction described in step 96.

These phosphate ions next play an important part in a further development, as CoA again does.

Another intermediate product in the glycolysis path, dihydroxyacetone phosphate (DHAP), acquires a

phosphate ion in its genesis and can change to glycerol-3-phosphate or back again with the help of an

enzyme and NAD or NADH2. Glycerol-3-phosphate is mostly the same as the three-carbon glycerol

except that a phosphate is substituted for the hydrogen of an end hydroxyl group.

Glycerol-3-phosphate (from Wikimedia Commons).

Through additional interactions, some involving CoA and acyl transferase, today bring three

long-chain fatty acids into contact with glycerol-3-phosphate, linking them into phosphatidic acid andthen into phospholidic acid.

O O

|| ||

CH2O C R CH2O C R1

| O | O

| || | ||

CH O C R CH O C R2

| O | O| || | ||

CH2

O

P

O

CH2

O

P

O

R3| |

O O

Phosphatidic Acid Phospholidic Acid

In the structural formulas above, the Rs refer to each fatty acid. In animals, including us, R3 may

be serine, ethanolamine, choline, inositol, or diacylglycerol (a second glycerol with two fatty acids and

an extra hydrogen atom). Thus, the ultimate effect of substituting a phosphate group on the carbon in


15/49

phosphatidic acid and then attaching more to the phosphate group is simply inserting the phosphate

group between the three-carbon saccharide-alcohol and R3.

The exact first use of this resulting structure, or something like it, is not yet certain. It may have

assisted in providing structures to direct multiple interaction pathways, to attach to sensors to keep

them in their relative positions, or for some other function. We also cannot be entirely certain of the

precise formulas of these lipids in their beginnings, but it likely was somewhat similar to the current

ones. (The phosphate insert and R3 change will appear again in step 100.)

Step 98. Polarity.

In step 97, phosphoglycerolipids came into existence and doubtless performed some useful

function, perhaps storage protected from phosphates. Lipids generally contain long-chain, unbranched,

unsaturated hydrocarbon chains (long in this context means 14-22 carbon atoms, which is tiny

compared to the nucleic acids, proteins, and saccharides). They are held together by the polar

(ionizable) glycerol molecule as in step 97 and may be associated with phosphates, proteins (as in

lipoproteins), and other molecules.

Today, they perform a wide range of functions. But when they were new, they were probably

only adapted and used for a very limited set of functions. Yet once the polar phosphates and glycerolwere associated with these molecules with long, non-polar carbon chains, they necessarily would tend

to associate with each other and naturally, spontaneously form closed structures, their non-polar ends

turned inward to avoid polar water, and their polar ends associating with the watery surroundings.

Polar, in this sense, refers to the electrical or valence ability of some atoms and molecules to

attract or repel other molecules and to interact with water, and hence often associated with ionization

and acid-basic interactions. Non-polarrefers to the lack of this kind of affinity. Polar atoms and

molecules easily dissolve in water, while non-polar ones more readily dissolve in oils and other non-

polar solvents.

A period of time (perhaps not too long) doubtless involved developing affinities between some

special lipids and some special proteins, such as sensors. In some cases, such alliances exist today as

part of the sensor-reactor system. But next came a great, further step.

Step 99. A new level of lipid organization.

In this step, a structure similar to those discussed in recent steps seems to have arisen. Instead

of lumping together in a lipid droplet in a protobions saccharide-enclosed yard, a way was found to

organize some phospholipids into two opposite-facing layers. This became possible by arranging two

layers of phosphoglycerolipid molecules in closed, hollow spheres, perhaps associated with the protein

sensors. The two layers had to face in opposite directions, one outward, one inward. Each molecules

had a polar end (the phosphate) and later a head, facing water on the outside and inside. Later, these

spheres coalesced into one membrane enclosing the entire inner yard of the bion. The long, non-

polar carbon chains or tails grouped facing each other to avoid touching water.

As long as lipid molecules had remained few, they could only lump together in solid lipid

droplets, but now apparently they became more numerous, and perhaps other factors helped form this

thin double layer. Possibly the phospholipids first collected on the capsule, expanding from there, but

probably not. At any rate, at least one TT did accomplish this total enclosure of the space inside the

saccharide-wall-enclosed are, with a colossal result. There now were true cells (or perhaps only partial

ones, with surrounding rock the only boundary in some directions, for a while).

A period of adjustment, of course, was necessary to adapt all the parts of a now complex bion,

adjusting sensors, lipid, enzymes, production pathways, lipoproteins, glycoproteins, and other special


16/49

molecules to the new system, enabling some sensors to become full-fledged pores, a structure toward

which they had been developing, and closing off the new cell more nearly to a specially refined degree

to some large molecules and welcoming others more efficiently. The boundary between the Ocean and

the bion became more precise, comprehensive, and effective.

Step 100. The new empire: the first prokaryote.

Creation of a genuine cell certainly introduced the new biological empire of prokaryotes. These

all have outer membranes like that just introduced; dsDNA genomes, normally in the form of a

continuous loop, thus safe from erosion of the end; some degree of metabolism; often support-proteins

associated with the DNA; the whole range of specialties evolved before this (except in later parasites);

and became more efficient, more able, and more mobile than any protobion. One result of this new

kind of bion became increasing enclosure of resources and increasing competitive pressure on the older

protobions.

Today, no protobions have been reported living independently, using the more recently

discovered of the old techniques described throughout this volume. Did they die off? Some probably

did. Others adapted by finding ways to break into the new cells enclosures to take advantage of the

new and more concentrated resources contained within. These adapted protobions are the viruses,which remain about an order of magnitude more numerous than the prokaryotes (i.e., outnumbering

prokaryotes 10 to 1, more or less). Perhaps a few still survive in the old free-range way, but humans

cannot live where they do and mostly are not concerned with whether they continue to do so now.

None have been sought; none have been found.

Only two kingdoms are known of these new prokaryotes, the archaea and the bacteria, but they

appear descended from the first cell, a particularly successful TT. Archaea use histone support-proteins,

as we do, with their DNA; the bacteria do not. Both have the saccharide wall (in most cases) and the

membrane surrounding the cell just within that. But the membranes are not exactly alike. Still, they are

similar enough to suggest something about the original membrane.

Phosphatidyl-Ethanolamine, a glycerophospholipid found in biological membranes (from Wikimedia Commons).

Comparing the main lipid molecules of these two kingdoms suggests several inferences. But

before drawing those inferences, let us first examine what general features they have in common. First,they both have, as suggested above and in previous steps, (1) hydrocarbon chains with non-polar far

ends (from water), (2) middle sections consisting of a three-carbon glycerol indirectly derived from

glycolysis, and (3) polar or head ends containing one phosphate group each, as mentioned previously.

It is not certain, but, since this much is common to both groups, this much probably was also true of the

original TT version.

Because the middle linking section of each of these phospholipids is (4) glycerol, it has three

carbon atoms singly bound to each in series, with two carbons also bound to a non-polar chain. Again,


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being common to both kingdoms, this feature is likely to have been part of the original version. (5)

Further, because singly bound atoms may rotate on their bond to each other, the glycerol carbon on one

end of the glycerol is rotated to place the phosphate group on the end of the whole molecule, facing

in the opposite direction from the hydrocarbon or lipid-chain end of the molecule, thus enhancing the

polarity of the whole molecule. Once again, these two features are common to the membrane systems

of both kingdoms of the prokaryote-empire. (The quotation marks around end are present because

the phosphate group of this end-carbon is not exactly at the end of the whole molecule.) Actually, (6) a

short, two-carbon chain is linked to the phosphate, still farther from the middle glycerol, and, beyond

that, (7) a still further attachment, consisting of an amine group (-NH3 in bacteria and -NH3+ in archaea).

The part of the polar end on the side of the phosphate group away from the glycerol is called the

head.

Phylogenetic tree of life showing the diversity of the prokaryotes bacteria and archaea compared to eukaryotes

(from Wikimedia Commons, article Prokaryote).

The original source covered in step 97 does not show either of these amine groups but seems to

represent eukaryotes, a later empire (including us) and hence is less persuasive. It is therefore inferred

that this little extra bit on the third (short) chain was probably in the original phospholipids evolved by a

TT, but ordinarily an amine group linked by one bond to a molecule is shown asNH2, because nitrogen

only has three potential bonds, so it is shown that way in the diagram. So the polar or phospho- end of

the original TT phospholipid molecule was as follows:

glycerol end carbon phosphate group two carbon mini-chain amine group

My sources do not identify the function of polar-end short-chain carbon atoms or the amine.

Perhaps these two extra carbons reduce the likelihood that the phosphate group will be damaged or

attracted away from the phospholipid molecule. The amine might conceivably do the same protective


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job but for the extra carbons, or perhaps it may make that end more strongly polar. Chemical tests

could answer that question.

Now, jumping back to the glycerol link between polar and non-polar ends, consider the number

of hydrogen atoms bound to each of the three glycerol carbon atoms. The third or end carbon linking to

the polar end uses one of its four potential bonds to make that link, a second to bind to the middle

carbon atom, and the remaining two to hold two hydrogen atoms. This is shown in the source and is

chemically reasonable. It matches in both ancient cellular kingdoms. The carbon on the other end of

the glycerol is in the same situation and does the same in both ancient cellular kingdoms. (8) That was

thus the original arrangement.

The middle carbon binds to both ofits partner carbons in glycerol (using two bonds) and a

third bond links it to a long-chain hydrocarbon. That leaves that middle carbon with only one more

potential bond so it could only bind to one hydrogen atom. My source shows this for bacteria but shows

two hydrogen atoms bound to the comparable carbon in archaea. This would require five bonds which

carbon does not have. The chemically logical conclusion is that (9) the middle carbon in both kingdoms

can only hold one hydrogen and that such was the arrangement in the original, successful molecule of

this type. Now, both types of prokaryote contain two long-chain hydrocarbons so (10) that is likely the

original system.

Divergences, however, do exist between the hydrocarbon chains of the two prokaryotekingdoms. One is that in archaea, both non-polar chains are like each other (both entirely saturated

with hydrogen atoms), while in bacteria they differ in one way. The non-polar carbon chain linked to the

middle carbon atom of glycerol has a double bond between two chain carbons in the middle of the

chain, while the other chain totally saturated. With only two persuasive kingdoms to consider, which is

more likely the original version? Consider these factors. First, making the chains alike is simpler than

making them differ for a bion. Second, for the empire as whole, three out of four (75%) of the chains

are fully saturated (weighting each lineage equally). Also, a fully saturated chain can be unsaturated

later by most cellular bions. None of these considerations is overwhelming, nor are even all three

together, but, since all three lean the same way, it seems more probable that (11) they all started with

both non-polar chains fully saturated.

Next, consider the long hydrocarbon chains. Among prokaryote kingdoms, (12) thosecontinuous chains differ between the kingdoms. In archaea both chains are 16 carbon atoms long,

matching not only each other but also palmitate, the version in humans membrane phospholipids. We

are in the third empire, eukaryotes, which seem to have arisen later from an existing kingdom. Because

both archaea and eukaryotes share histone as the supporting category of proteins for association with

the main DNA strands, and that is a very basic matter, it is reasonable to believe that we are descended

from an archaean ancestor.

On the other hand, in bacteria, the long-chain non-polar ends of membrane phospholipids both

have 18 carbon atoms. With one ancient kingdom on each side, this information is insufficient to judge

which (if either) matches the earlier common ancestor. The difference between 16 and 18 in a

repetitive series cannot be based on a standard of simplicity. The evidence from the third empire,

eukaryotes, really changes little, because it is descended from archaea and so kept that much of this

molecular structure. So far, the evidence is unpersuasive either way.

There is, however, another difference. While bacterial membrane phospholipid has only

unbranched carbon chains, the archaeal equivalent carries four short (one-carbon) branches on each of

its two non-polar chains, bringing the total number of carbons in the hydrocarbon portion of the

molecule to 20! While the difference in simplicity or complexity between unbranched and a few

branches is not great, it favors the unbranched version, particularly because other bions with different

lengths of chain, both more and less, also tend to have unbranched chains. I conclude that (13) the

original version was unbranched.


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Besides, if an unbranched eukaryote form descended from an archaean in a largely unbranched

biosphere (for such molecules), archaea themselves likely also once had unbranched non-polar-end

carbon chains. How else could later descendants have such unbranched chains? Hence, eukaryotes

branched off from archaea before they had branched chains and thus inherited unbranched chains from

them; the archaea therefore acquired their branches after the separation.

Now (14) back to the numbers of carbon atoms, and the cause and influence of the branching.

Perhaps the connection between the two was that, at some point, both had 18 carbons in their chains,

but some chemical change brought about a shift of the last two unbranched carbon atoms on each

chain, moving them to the status of branches, followed by a failure in the system to stop there, bringing

the total to two more branches besides that, equaling 20 carbons in all. This is too speculative to permit

confidence from the present evidence but seems possible, so we shall leave it there for now.

Still another difference exists between those two old prokaryotic kingdoms. (15) In bacteria, the

long carbon chains bind to the glycerol links by carboxyl groups (which is the part making these chains

into fatty acids). Archaea, however, make this link with just an oxygen atom. As to chemical simplicity, I

am unsure which seems more primitive, but the evidence of the eukaryotes, in which these components

are fatty acids, again implies the archaea must have changed their system since separating from the

eukaryotes, but other explanations are possible. I assume the acid guise was the original TT form.

Finally, (16) these membrane-phospholipid molecules appear in one form in bacteria, asdescribed, but in two distinct forms in archaea. One form is the one discussed above. A second form is

at least twice as long, with both ends polar, and the whole distance between two continuous non-polar

chains, rather like two standard molecules attached back to back (tail to tail), running through the full

thickness of the membrane. Some advantage may well exist in having this alternate form, but

considerations of evolutionary economy, conservatism, and simplicity suggest that the single-model

system probably preceded the multiplication and diversification that are typical in biological evolution.73

73According to Wikipedia, article Last universal ancestor, the following characteristics are shared by all living

organisms and would thus characterize the ancestral cell:

The genetic code was based on DNA

o The DNA was composed of four nucleotides (deoxyadenosine, deoxycytidine, deoxythymidine

and deoxyguanosine)...

o The genetic code was composed of three-nucleotide codons, thus producing 64 different codons.

Since only 20 amino acids were used, multiple codons code for the same amino acids.

o The DNA was kept double-stranded by a template-dependent DNA polymerase.

o The integrity of the DNA was maintained by a group of maintenance enzymes, including DNA

topoisomerase, DNA ligase and other DNA repair enzymes. The DNA was also protected by DNA-

binding proteins such as histones.

The genetic code was expressed via RNA intermediates, which were single-stranded.

o RNA was produced by a DNA-dependent RNA polymerase using nucleotides similar to those of

DNA with the exception ofthymidine in DNA was replaced by uridine in RNA.

The genetic code was expressed into proteins.

All other properties of the organism were the result of protein functions. Proteins were assembled from free amino acids by translation of an mRNA by ribosomes, tRNA and a

group of related proteins.

o Ribosomes were composed of two subunits, one big 50S and one small 30S.

o Each ribosomal subunit was composed of a core ofribosomal RNA surrounded by ribosomal

proteins.

o The RNA molecules (rRNA and tRNA) played an important role in the catalytic activity of the

ribosomes.

o Only 20 amino acids were used, to the exclusion of countless other amino acids.
http://en.wikipedia.org/wiki/Genetic_codehttp://en.wikipedia.org/wiki/DNAhttp://en.wikipedia.org/wiki/Nucleotidehttp://en.wikipedia.org/wiki/Deoxyadenosinehttp://en.wikipedia.org/wiki/Deoxycytidinehttp://en.wikipedia.org/wiki/Deoxythymidinehttp://en.wikipedia.org/wiki/Deoxyguanosinehttp://en.wikipedia.org/wiki/Codonshttp://en.wikipedia.org/wiki/Amino_acidshttp://en.wikipedia.org/wiki/DNA_polymerasehttp://en.wikipedia.org/wiki/DNA_topoisomerasehttp://en.wikipedia.org/wiki/DNA_topoisomerasehttp://en.wikipedia.org/wiki/DNA_ligasehttp://en.wikipedia.org/wiki/DNA_repairhttp://en.wikipedia.org/wiki/Histoneshttp://en.wikipedia.org/wiki/RNAhttp://en.wikipedia.org/wiki/RNA_polymerasehttp://en.wikipedia.org/wiki/Thymidinehttp://en.wikipedia.org/wiki/Uridinehttp://en.wikipedia.org/wiki/Proteinshttp://en.wikipedia.org/wiki/Amino_acidshttp://en.wikipedia.org/wiki/Translation_%28genetics%29http://en.wikipedia.org/wiki/MRNAhttp://en.wikipedia.org/wiki/Ribosomeshttp://en.wikipedia.org/wiki/TRNAhttp://en.wikipedia.org/wiki/50Shttp://en.wikipedia.org/wiki/30Shttp://en.wikipedia.org/wiki/Ribosomal_RNAhttp://en.wikipedia.org/wiki/Ribosomal_proteinshttp://en.wikipedia.org/wiki/Ribosomal_proteinshttp://en.wikipedia.org/wiki/Amino_acidshttp://en.wikipedia.org/wiki/Amino_acidshttp://en.wikipedia.org/wiki/Ribosomal_proteinshttp://en.wikipedia.org/wiki/Ribosomal_proteinshttp://en.wikipedia.org/wiki/Ribosomal_RNAhttp://en.wikipedia.org/wiki/30Shttp://en.wikipedia.org/wiki/50Shttp://en.wikipedia.org/wiki/TRNAhttp://en.wikipedia.org/wiki/Ribosomeshttp://en.wikipedia.org/wiki/MRNAhttp://en.wikipedia.org/wiki/Translation_%28genetics%29http://en.wikipedia.org/wiki/Amino_acidshttp://en.wikipedia.org/wiki/Proteinshttp://en.wikipedia.org/wiki/Uridinehttp://en.wikipedia.org/wiki/Thymidinehttp://en.wikipedia.org/wiki/RNA_polymerasehttp://en.wikipedia.org/wiki/RNAhttp://en.wikipedia.org/wiki/Histoneshttp://en.wikipedia.org/wiki/DNA_repairhttp://en.wikipedia.org/wiki/DNA_ligasehttp://en.wikipedia.org/wiki/DNA_topoisomerasehttp://en.wikipedia.org/wiki/DNA_topoisomerasehttp://en.wikipedia.org/wiki/DNA_polymerasehttp://en.wikipedia.org/wiki/Amino_acidshttp://en.wikipedia.org/wiki/Codonshttp://en.wikipedia.org/wiki/Deoxyguanosinehttp://en.wikipedia.org/wiki/Deoxythymidinehttp://en.wikipedia.org/wiki/Deoxycytidinehttp://en.wikipedia.org/wiki/Deoxyadenosinehttp://en.wikipedia.org/wiki/Nucleotidehttp://en.wikipedia.org/wiki/DNAhttp://en.wikipedia.org/wiki/Genetic_code


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o Only the L-isomers of the amino acids were used. Glucose could be used as a source of energy and carbon; only the D-isomer was used.

ATP was used as an energy intermediate.

There were several hundred protein enzymes which catalyze chemical reactions that extract energy from

fats, sugars, and amino acids, and that synthesize fats, sugars, amino acids, and nucleic acid bases using

arbitrary chemical pathways.

The cell contained a water-based cytoplasm that was surrounded and effectively enclosed by a lipidbilayer membrane.

Inside the cell, the concentration ofsodium was lower, and potassium was higher, than outside. This

gradient was maintained by specific ion transporters (also referred to as ion pumps).

The cell multiplied by duplicating all its contents followed by cellular division.

b. Nature of cellular membranes

We have seen that nucleotides, amino acids, and simple sugars form chemical bonds with each

other in making polymers such as nucleic-acid strand, proteins, and polysaccharides. Fatty acids behave

differently. They can form chemical bonds with non-lipids, but they do not ordinarily form chemical

with each other in forming either lipid-fuel droplets or cell membranes.

Thus, they do not form a solid, continuous, textured sheet of chemically bound or linked

phosphoglycerolipids in the cell membranes. Instead, they each merely float freely, relying entirely on

the electrochemical properties of their polar ends and long, non-polar carbon chains for positioning.

The polar end, in effect, dissolves in water. It does not break up. It remains a linked unit within its

molecule. But it establishes that electrochemical relationship with water molecules that any water-

soluble molecule establishes, and hence tends to touch water if possible. The non-polar end does not

do this, but instead establishes a solute relationship with other non-polar molecules (or parts of

molecules) as if it were dissolving in a non-polar solvent.

Cell membrane, with blue indicating protein structures, orange and yellow the phospholipids (from Wikimedia

Commons).

The result, in the case of lipid droplets, is merely to gather the fatty-acid chains into a clump,

like the blobs of butterfat on milk resulting from churning, except that butterfat blobs float to an air-

water interface, flattening, while the droplets inside bions find and have access to no air, so those
http://en.wikipedia.org/wiki/Chirality_%28chemistry%29http://en.wikipedia.org/wiki/Glucosehttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Isomerhttp://en.wikipedia.org/wiki/Adenosine_triphosphatehttp://en.wikipedia.org/wiki/Enzymeshttp://en.wikipedia.org/wiki/Sodiumhttp://en.wikipedia.org/wiki/Potassiumhttp://en.wikipedia.org/wiki/Ion_transporterhttp://en.wikipedia.org/wiki/Cellular_divisionhttp://en.wikipedia.org/wiki/Cellular_divisionhttp://en.wikipedia.org/wiki/Ion_transporterhttp://en.wikipedia.org/wiki/Potassiumhttp://en.wikipedia.org/wiki/Sodiumhttp://en.wikipedia.org/wiki/Enzymeshttp://en.wikipedia.org/wiki/Adenosine_triphosphatehttp://en.wikipedia.org/wiki/Isomerhttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Glucosehttp://en.wikipedia.org/wiki/Chirality_%28chemistry%29


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droplets are spherical, with as many carbon chains inside as possible. It is a case of oil and water do

not mix, except that it is not a question of mixing but of dissolving. Put a drop of cooking oil gently on

water and the result will be the same it remains intact. (Of course, if its strikes the surface too hard, it

may break into pieces, but it does not dissolve.)

In the case of cell membranes, these properties of the phosphate group, a polar portion of the

molecule, make it behave as described above for molecules that can dissolve in water. It does not break

up or break off the rest of the molecules, but tends to establish relationships with available water

molecules, as though it were dissolving. Chemically, that is what dissolving always is. Dissolving does

not destroy a molecule. Dissolve salt or sugar or acid in water and you will still taste them, even when

the separation of their molecules from one another makes them invisible to the naked eye.

The long carbon chain also behaves as described above. It remains intact, but tends to associate

with other floating non-polar molecules. The result is that such molecules as phospholipids collect

spontaneously, with no other influences than these characteristics, so that, if possible, all long carbon

chains associate with each other, avoiding the water as though it were dangerous to them (it is not).

This behavior leaves the polar phosphate groups touching the water on both surfaces of this double-

layer, associating with water molecules. It is as if both ends of the phospholipid molecules have

dissolved in a compatible solvent, in one case, water, while in the other case, other copies of

themselves.Behaving in this way is summarized by being called amphipathic behavior (attracted or

compatible, or literally feeling drawn in two different directions at the same time). This quality is

fundamental to the nature and functions of fatty acids in bions, especially in their membranes.

A cell membrane, therefore, is a phalanx or rank (like soldiers standing in formation, side by

side) of phospholipids with the phosphate, polar ends attracted to (facing) the open Ocean (or its

equivalent inside the host bion of a parasite); a second phalanx with its phosphate ends facing the

inner bit of ocean inside the cell (as an army formation might if suddenly faced by enemies to both

front and back); and the non-polar, long lipid carbon chain parts of the molecules between these two

fronts facing in opposite directions, avoiding contact with water. This external membrane must

extend completely around the cell, with no openings, like a bubble or balloon. Also like a bubble or

balloon, if some molecules are destroyed, the membrane simply shrinks (within limits) in the process ofadjusting their distances from each other, so they can stay shoulder to shoulder and avoid water

contact with the long carbon chains.

Because of this, without any complicated systems of design, the membrane automatically and

instantly repairs minor losses of molecules. On the other hand, if additional phospholipid molecules of

similar type become available, they will shoulder their way into line and the membrane will grow as

needed. Under special influence (in cases of reproduction), the membrane may separate into two

separate, smaller membranes, each still remaining complete. The most natural shape for a membrane,

as for a bubble, unless it is attached to another, is spherical, but the external polysaccharide wall can

force it into other shapes, like a sausage in its rather different enclosure.

Cell membranes are typically described as a lipid bilayer (meaning the same as above).

Proteins of various kinds and functions, including the sensor-reactor systems described

previously, some in the form of mechanisms that can open, convey, and close, others simply sending

and reporting back to a responding mechanism, can push their way into the membrane, stay in it,

usually extending through both layers, to perform their duties, and other items can also be included.

Part of the fine adjustment needed to let the membrane and components and attachments coordinate

at top efficiency were completed quickly because they were already somewhat pre-adapted, as

suggested in earlier stages, but more remained to be done, as the next volume is intended to outline

briefly.


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At this point, our history of our protobion ancestors ended, as one of them became the first

prokaryote, the first bion surrounded by or wearing a cell membrane, as described above. They later

sometimes returned partway to their protobion ancestry in emergencies by emptying most of their

inner water, strengthening their cell enclosures, and nearly stopping the continuous and extensive

chemical changes, such as metabolism and reproduction, until the emergency passes and the more

active biology can reassert itself. This is the prokaryote spore form. (Of course, protobion history

continues, but that is not our history, except to the extent that these descendants of the protobions,

which are our remote cousins descended from our ancestors, interact with us now.)

Whether or not explicitly stated in each step, each of the steps of our ancient protobion

ancestors set forth in this volume has left its effect on each of us today, in most cells of our bodies, even

though the protobions as such did not yet have cellular membranes. The processes, substances, and

structures that they developed are still used by us, often with further modifications and a few

exceptions. For example, we no longer have saccharide cell walls around our cells, and acquisition of

DNA reduced the role of RNA slightly. But still, the broad picture remains the same, as far as it goes.

And this is only the beginning.

Sphingomyelin, a sphingolipid (from Wikimedia Commons).

.

Cholesterol, a lipid found in eukaryotes (from Wikimedia Commons).

(Later ancestors developed other amphipathic lipids which became parts of their membranes.

One of these is called sphingolipid. Without details of head group or carbon chains, the figure below

suggests its general characteristic structure. The structural formula for a general case of the other,

cholesterol, also shown, is characteristic of eukaryotes (including us). It is today a vital part of our cell

membranes, but its types need to be kept in proper balance, as nutritionists tell us. Cholesterol is an

example of a sterol, and, of course, the best known of them to most of us. A basic function of

cholesterol is stiffening cell membranes. The oldest evidence of cholesterol formation, and hence likelyour earliest eukaryote ancestor, has been found in rock 2700 millads or 2.7 billion years old.)

[insert scanned graphics here]


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Chapter N. Summary and conclusions for volume I.

Before biology.

We briefly considered in chapter C a few general characteristics of reality before (and later,

away from) the Sun, Earth, and Earth biology, including the formation of stars and other celestial bodies,of atoms other than hydrogen, the general nature of systems, of matter and energy, the many

generations of large stars that had to form and break up before Earth could be as it became, and such

like. Chapter D covers the formation of Sun, Earth, and a bit of their early nature. This is relevant

because we arose from Earth and are now finely adapted to it. The nature of Earth largely (but not

entirely) determined our nature.

We are made of stardust but, more to the point, we are made of what makes at least the

uppermost layers of the Earth: air, water, light elements from the upper rows of the periodic table

(hydrogen, carbon, oxygen, nitrogen, sulfur, and phosphorus), and some traces of metal-ion catalysts.

We have seen that a simple chemical experiment73 in two flasks, starting from a small

representation of the most common early air elements and molecules, provided with heat and sparks

(as artificial lightning), in two weeks yielded a small ocean (liquid water), a considerable range of what

now are largely biological molecules (including seven amino acids, two of which are part of biology

today), ammonia, etc., and a few larger biomolecules, and a relatively great mass of tarry muck at the

bottom. On the early Earth, these all were clearly the case, with a reducing atmosphere, lacking

significant free oxygen, the presence of amino acids, and a tendency for these to form rings, some of

which had catalytic properties assisting other pre-biological (but toward biological) interactions.

73The Miller-Urey experiment that sought to demonstrate that conditions on the early Earth allowed chemical

reactions that ultimately led to biology. See Miller, S.L. and H.C. Urey. 1959. organic Compound Synthesis on the

Primitive Earth in Science 130 (3370): 245-251. Doi:10.1126/science.130.3370.245. See also Cleaves, H.J., J.H.

Chalmers, A. Lazcano, S.L. Miller, and J.L. Bada. 2008. A Reassessment of Prebiotic Organic Synthesis in Neutral

Planetary Atmospheres, in Origins of Life and Evolution of Biospheres 38 (2): 105. Doi.10.1007/s11084-007-9120-

3. After Millers death, reanalysis of the sealed vials from the original experiment showed that there were well

over 20 different amino acids, not just the few Miller first reported. The atmosphere of this early period is now

thought to have differed from what was thought in the 1950s. Later experiments more or less replicated the

classic one but took into account these later views.

Geological studies have confirmed that these results also describe the early real world, the tar

appearing in the earliest rock as multiple, varied, and mixed carbon chains of various lengths, branched

and unbranched, formed by non-biological processes (as shown by equal presence of both chiral forms).

Though not mentioned earlier in this text, it has been found that the copious iron deposits and iron ions

in the Ocean back then assisted the aggregation of amino acids into chains and circular peptides, which

in turn then assisted the steps leading to RNA and the first bions.

The chemically reducing air, the slightly acid Ocean, the heat and other steady resources

provided along the deep-Ocean ridges of geothermic vents and plumes not only pushed pre-biologicalchemistry toward biology, but also gave it a relatively steady and protected environment, less disturbed

by the heavy bombardment of Earth from outer space by particles and other celestial bodies during the

first few hundred millads after the Earth crust mostly hardened.

We have seen that this early source of heat, catalysts, other resources, and safety, allowed time

for competitive and cooperative processes to sort the molecules into what became a reproducing bion.

The heat and resource source drove the system toward what we call biology. Earth did not stagnate into


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equilibrium, nor did its chemistry, once the temperatures allowed chemistry to go to completion and

stop. Biology requires a degree of balance, but also a degree of dynamism.

As we have seen, the origin and foundation of biology is chemistry, especially organic chemistry.

Ocean chemistry is complex, because of the large number and varied quantities of different atoms and

molecules, and the varied conditions in different parts of the Ocean, all ultimately affecting each other,

but some neither immediately nor equally. By two human generations ago, students of the origin of

biology recognized that the beginning must have been a self-reproducing molecule.

By one generation ago, the more perceptive recognized that the molecule was RNA. Since then,

a considerable range of writers has quarreled with this inference, presenting a wide and largely

implausible collection of substitutes, from clay crystals to magic lipid bubbles, to actual alternative

molecules, but in fact none of these has ever been found to have had any such role in biology. The RNA

world was the simple beginning; the first bion was an RNA molecule, and RNA bions remain today, filling

the Ocean and other bodies of water, and the soil.

This outcome may not seem inevitable from a glance at the chemical formula for RNA, but it

resulted from several factors. The nature of the component atoms and three molecular sections of a

nucleotide enables RNA to perform more than one function valuable for survival: (1) the ability to serve

as a template for, and to be formed against, another RNA molecule, i.e., to be reproduced by, and to

reproduce something roughly like itself (reproduction); (2) the ability to influence the behavior of itse

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