BIOCHEMISTRY LECTURES

Space-filling models of (A) palmitate (C16, saturated) and (B) oleate (C18, unsaturated). The cis double bond in oleate produces a bend in the hydrocarbon chain.

Figure 10-2 1

Figure 10-2 2

Mono- and Polyunsaturated Acids

Pages 343-345

The principle classes of storage and membrane lipids. All of the classes shown here have either glycerol or sphingosine as the backbone.

Figure 10-6, pages 348-349.

Absolute configuration of the glycerol 3-phosphate moiety of membrane lipids:

(A) H and OH, attached to C-2, are in front of the plane of the page, whereas C-1 and C-3 are behind it.

(B) Fischer representation of this structure. In a Fischer projection, horizontal bonds denote bonds in front, while vertical bonds denote bonds behind the plane of the page.

Figure 10-8 1

Figure 10-8 2

Figure 10-13a

Figure 10-9a

Allergic reactions

Prolonged hypersensitivity

Potent bronchoconstrictor

Chemotactic, eisonophils

Figure 10-12 1

Figure 10-12 2

Figure 10-13b

Figure 10-14

Like Figure 10-15Use in determination of structure, page 365.

Like Figure 10-16

Space-filling model of the trioleate ester of glycerol.

Monolayer of oil molecules at an air-water interface.

Phosphatidyl choline and sphingomyelin molecules

Figure 11-4a

Figure 11-4b

Bilayer Membrane

Space-filled model of a section of a highly fluid phospholipid bilayer membrane.

Diagram of a section of a bilayer membrane formed from phospholipid molecules.

Figure 11-4c

Figure 11-2

Experimentation and Study of Bilayer Membranes

Experimental arrangement for the study of planar bilayer membranes. A bilayer membrane is formed across a 1-mm hole in a septum that separates two aqueous compartments.

The permeability coefficients (P) of ions and molecules in lipid bilayer membranes span a

wide range of values.

Approximate the values for ethanol, C16 fatty acid, cholesterol, cholic acid, taurocholic acid.

Figure 11-6

Figure 11-9

Figure 11-17

Combination of Figures 11-16 a, b, and c.

Packing of fatty acids

The highly ordered packing of fatty acid chains is disrupted by the presence of cis double bonds. These space-filling models show the packing of (A) three molecules of stearate (C18, saturated) and (B) a molecule of oleate (C18, unsaturated) between two molecules of stearate.

Stages in the extraction of energy from foodstuffs.

More in Fig 17-3.

Carnitine acyltranferase I

Carnitine acyltranferase II

Malonyl CoA inhibits carnitine acyltransferace I

Like Figure 17-06.

Odd-chain fatty acids

Figure 17-18 1

Figure 17-18 2

Figure 17-18 3

Figure 17-18 4

Figure 17-18

Figure 17-19 1

Figure 17-19 2

Figure 17-20

1. Synthesis takes place in the cytosol, in contrast with degradation, which occurs in the mitochondrial matrix.

2. Intermediates in fattv acid synthesis are covalently linked to the sulf-hydryl groups of an acyl carrier protein (ACP), whereas intermediates in fatty acid breakdown are bonded to coenzyme A.

3. The enzymes of fatty acid synthesis in higher organisms are joined in a single polypeptide chain called fatty acid synthase. In contrast, the degradative enzymes do not seem to be associated.

4. The growing fatty acid chain is elongated by the sequential addition of two-carbon units derived from acetyl CoA. The activated donor of two-carbon units in the elongation step is malonyl-ACP. The elongation reaction is driven by the release of CO2.

5. The reductant in fatty acid synthesis is NADPH, whereas the oxidants in fatty acid degradation are NAD+ and FAD.

6. Elongation by the fatty acid synthase complex stops upon formation of palmitate (C16). Further elongation and the insertion of double bonds are carried out by enzyme systems of the endoplasmic reticulum with the fatty acyl groups as CoA derivatives.

Schematic diagram showing the proposed movement of the biotin prosthetic group from the site where it acquires a carboxyl group from HCO3

- to the site where it donates this group to acetyl CoA.

Biotin carries the CO2 to the acetyl CoA

Acetyl CoA carboxylase, which catalyzes the committed step in fatty acid synthesis, is a key control site.

See Figure 17-12

Like Figure 21-4.

See Figures 21-2 and 21-3.

Citrate transport system. The system achieves net transport of acetyl CoA from the mitochondrion to the cytosol and net conversion of cytosolic NADH to NADPH. Up to two molecules of ATP are expended for each round of the cyclic pathway.

Figure 21-9. See Figure 21-10.

Figure 21-11

Desaturation

The conversion of C16 to C16:1 9 in eukaryotes is catalyzed by stearoyl-CoA desaturase in a reaction sequence that also involves cytochrome b5 and cytochrome b5 reductase. Two elections are passed from NADH through the chain of reactions as shown, and two electrons are also derived from the fatty acyl substrate. They are evenually placed on oxygen to make water. See Figure 21-13.

(Example of coupled oxidation; a couple of substances are oxidized)

positions 6,9 or 3,6,9 from plants. We must get fatty acids

withs in

To make prostaglandins and leucotrienes, animals useC20 fatty acids with 3,4 or 5 cis s in key positions.

CH3

1 2 43 5 6 7 8 9 10 11 12 13 14 15 16 17 18

18 17 1516 14 13 12 11 10 9 8 7 6 5 4 3 2 1

C16

9

Animals and plants place first cis at 9

9

C18

6

new

9

by –CH2– from an existing , towards the –COO- group,regardless of the length (C16, C18, C20) of the fatty acid.

Animals and plants can place a subsequent , separated

existing

9

by –CH2– from an existing , towards the CH3– group.Only plants can place a subsequent , separated

existing

12

new

9

9

9

9

6

3 6

In plants C18:0

C18:1

C18:2

C18:3

In animals or plants

6 9 12 15

6 9 12

6 9 12

6 9

PGs1

PGs2

C18:2

C18:3

C20:3

C20:4

C18:3 3,6,9 C18:4 3,6,9,12 C20:5 3,6,9,12,15

3 6 9 12 15PGs3

Arachidonate

Arachidonate is the major precursor of eicosanoid hormones. Prostaglandin synthase catalyzes the first step in a pathway leading to prostaglandins, prostacyclins, and thromboxanes. Lipoxygenase catalyzes the initial step in a pathway leading to leukotrienes. See Figures 10-18 and 21-15.

C20:4 6,9,12,15

Synthesis of PGH2 from arachidonate

Synthesis of PGH2, a key prostaglandin, from arachidonate. PGH2 is the precursor of other prostaglandins, prostacylin, and thromboxanes. See page 801.

COX

Important eicosanoids

Vascular endothelial cells:

vasdilatory

inhibits platelet aggregation

Platelets:

aggregates platelets

White blood cells,

mast cells

inflammatory,

allergic

Aspirin

COX

Structure of the active site of prostaglandin H2 synthase (COX)

Cyclooxygenases

COX 1: constitutive

- in plateletts

- in gastrointestinal epithelial cells

COX 2: induced in inflammatory process

Selective inhibitors – non steroidal (NSAIDs) ?

How do steroids reduce inflamation?

See Celebrex and Vioxx, page 803.

See Figures 21-17 and 21-18

Figure 21-24. Read page 809.

Figure 21-27

Figure 21-28

Figure 21-31 1

Figure 21-31 2

Figure 21-31 3

N-Acetylneuraminate

Read page 356.

Figure 21-4

Figure 21-34 1

Figure 21-34 2

Figure 21-34 3

Figure 21-44

Figure 21-45

Figure 21-35

Figure 21-36

Figure 21-37

Figure 21-38

Figure 21-46

Figure 21-48

Figure 21-39

Figure 17-2

Figure 17-1

Figure 21-39

Figure 21-40

All the carbon atoms and hydrogen atoms of fat and cholesterol can be from glucose!