Nisa Rachmania Mubarik Major Microbiology Department of ... · Amino acids can be classified as...

Microbial Physiology Nisa R Mubarik

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Nisa Rachmania MubarikMajor Microbiology Department of Biology, IPB


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ValineTyrosineTyrptophanSerineThreonineProline

Phenylalanine*GlycineMethionine*Glutamine

LysineGlutamateLeucineCysteine

IsoleucineAspartateHistidineAsparagineArginine*Alanine

EssentialNonessential


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http://www.personal.psu.edu/staff/m/b/mbt102/bisci4online/chemistry/chemistry8.htm


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Primary - exact sequence of amino acids before folding. Secondary - simple folding create simple structures. Tertiary - folding results in complex 3D structures. Quaternary - multiple 3D subunits organized into a bigger structure.

Four levels of protein structure


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Based on chemical similarities and only few starting compounds, all amino acids can be regarded as members of five families:

1. The glutamate family starting with alpha-ketoglutarateThe amino acids glutamate, glutamine, proline and arginine are membersof this family

2. The aspartate family with the starting compound oxaloacetateThe amino acids apartate, asparagine, threonine, isoleucine and methionine are counted among this group.

3. The alanine-valine-leucine group (pyruvate)

4. The serine-glycine group (3-phosphoglycerate)

5. The family of aromatic amino acids (phosphoenolpyruvate and erythrose-4-phosphate, an intermediate in the pentose phosphate pathway).


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http://www.biologie.uni-hamburg.de/b-online/e19/19e.htm


7http://www.biochemj.org/bj/388/0669/bj3880669.htm


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The glutamate familyGlutamate is accordingly the amino acid generated first. Glutamate itself can bind a further ammonium ion to form glutamine, a second amino acid. Both reactions are ATP-dependent. Very important for amino acid syntheses is a group of enzymes called aminotransferases. They are able to transfer an amino group (mostly that of glutamine) to an alpha-keto acid. Accordingly, they could also be said to be the distributors of amino groups.

Glutamate dehydrogenasereaction: The starting compounds are alpha-ketoglutarate and NH4+.

Glutamate synthetase reaction: starting compounds are glutamate and NH4+.


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Glutamate synthase reaction (a transamination). The amino group of an amino acid (glutamate) is transferred to an alpha-ketoacid (alpha-ketoglutarate).

Proline is generated by a ring formation under consumption of one molecule of NADH + H+, NADPH + H+ and ATP each.


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A pair of principal enzymes, glutamate dehydrogenase and glutamine synthatase, are found in all organisms and effect the conversion of ammonia into the amino acids glutamate and glutamine, respectively.

Amino and amide groups from these 2 substances are freely transferred to other carbon skeletons by transamination and transamidation reactions.


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The aspartate family with the starting compound oxaloacetate

The amino acids aspartate, asparagine, threonine, isoleucine and methionine are counted among this group. Aspartate is generated by the transaminationglutamate + oxaloacetate > alpha-ketoglutarate + aspartate

A cofactor in the methionine production is tetrahydrofolate (THF) that transfers a methyl group to the -SH group of homocysteine, the precursor of methionine. The result is the terminal -S-CH3 group of methionine.


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Lysine synthesis. Intermediates of the glutamate and the aspartate family are coupled in just the same way as in the arginine and asparaginesynthesis. Lysine can be generated in two ways. Both are named according to their most characteristic intermediates. Green algae, ferns and higher plants take one pathway, some green flagellates (euglenophyta) and fungi the other


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Branched chain amino acid and lysine biosynthesisBiosynthetic relationships among the branched chain amino acids


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The alanine-valine-leucine group (pyruvate)

Pyruvate is the starting compound, its amino derivative is alanine. Valine and leucine are synthesized independently of each other by elongation of the pyruvate chain, interconversion and subsequent transamination.

This group of essential amino acids are identified as the branched-chain amino acids, BCAAs. Because this arrangement of carbon atoms cannot be made by humans, these amino acids are an essential element in the diet.


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Feedback inhibition of valine, leucine and isoleucine biosynthesis


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The serine-glycine group (3-phosphoglycerate)

Serine is generated in a two-step reaction from 3-phosphoglycerate. The first step is an oxidation, the second a transamination.

Alternatively, 3-phosphoglycerate can also be dephosphorylated to generate hydroxyproline that is subsequently converted to serine by transamination. A path branches from serine to glycine in which the -CH2OH part of the serine side chain is split off and the C1 unit is accepted by the already mentioned tetrahydrofolate (THF). Another pathway results in cysteine. This means that cysteine can also be produced by at least two paths (the other was the degradation of methionine).


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The family of aromatic amino acids (phosphoenolpyruvate and erythrose-4-phosphate, an intermediate in the pentose phosphate pathway). A ring is formed via several intermediates. Both shikimate and the subsequent chorismate are important intermediates. The latter is the starting compound for three different pathways that lead to the end products phe, tyr and trp. An activated form of ribose phosphate (5-phosphoribosyl-alpha-pyrophosphate) is an intermediate of tryptophane synthesis. It has also a key position in the synthesis of histidine that is not discussed here and in that of purines and pyrimidines. It should only be mentioned that the biosynthetic pathway of histidine is unusual in that it is produced from a purine.

Alternative biosynthetic pathways. The starting compound shown in the picture to the left is an unstable intermediate that is generated from chorismate by the chorismate mutase. Chorismateis the aromatic amino acid precursor.


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Plants and microorganisms commonly synthesize tryptophan from shikimic acid or anthranilate. The latter condenses with phosphoribosylpyrophosphate (PRPP), generating pyrophosphate as a by-product. After ring opening of the ribose moiety and following reductive decarboxylation, indole-3-glycerinephosphate is produced, which in turn is transformed into indole In the last step, tryptophan synthasecatalyzes the formation of tryptophan from indole and the amino acid, serine.

The industrial production of tryptophan is also biosynthetic and is based on the fermentation of serine and indole using either wild-type or genetically modified E. coli. The conversion is catalyzed by the enzyme tryptophan synthase.


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Degradation of carbon skeletons of amino acids

The carbon skeleton remainings after deamination of amino acids can be used in various biosynthetic pathways as intermediates degraded by reactions coupled to the generation of energy

All amino acids can be degraded to CO2 and H2O by appropriate enzyme systems. All these systems involve, directly or indirectly, the formation of a dicarboxylicacid intermediate of the TCA cycle.


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Amino acid degradation to pyruvate


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Amino acids can be classified as glucogenic or ketogenic

Glucogenic Amino Acids

Glucogenic amino acids can be degraded to pyruvate or an intermediate in the Krebs Cycle. They are named glucogenic because they can produce glucose under conditions of low glucose. This process is also known as gluconeogenesis, or the production of "new glucose." Amino acids form glucose through degradation to pyruvate or an intermediate in the Krebs Cycle.

The intermediates can then be converted to oxaloacetate, the main precursor for gluconeogenesis. The following amino acids are glucogenic: alanine, cysteine, glycine, serine, threonine, tryptophan, asparagine, aspartate, phenylalanine, tyrosine, isoleucine, methionine, threonine, valine, arginine, glutamate, glutamine, histidine, and proline.


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Ketogenic Amino Acids

In contrast, ketogenic amino acids can produce ketones when energy sources are low. Some of these amino acids are degraded directly to ketone bodies such as acetoacetate (see ). They include leucine, lysine, phenylalanine, tryptophan, and tyrosine. The other ketogenic amino acids can be converted to acetyl CoA. Acetyl CoA has several different fates, one of which is the conversion to acetoacetate. Acetoacetate cannot be used in gluconeogenesis, since acetyl CoA cannot be converted directly to oxaloacetate.

When energy sources are high, both glucogenic and ketogenic amino acids are converted to fatty acids through the intermediate acetyl CoA. Other amino acids that are degraded to intermediates in the Krebs Cycle are siphoned off into the production of urea.


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The urea cycle is part of the degradation pathway of amino acids. It converts the NH4

+ generated by amino acid degradation into urea. The first reaction of the urea cycle ― the condensation of ornithine and carbamaylphosphate -takes place in the mitochondrial matrix. Citrulline is then exported into the cytosol.

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