SUMMARY

24.1 Nitrogen Fixation: Microorganisms Use ATP and a Powerful Reductant to Reduce Atmospheric Nitrogen to Ammonia

Microorganisms use ATP and reduced ferredoxin, a powerful reductant, to reduce N2 to NH3. An iron–molybdenum cluster in nitrogenase deftly catalyzes the fixation of N2, a very inert molecule. Higher organisms consume the fixed nitrogen to synthesize amino acids, nucleotides, and other nitrogen-containing biomolecules. The major points of entry of NH4+ into metabolism are glutamine or glutamate.

24.2 Amino Acids Are Made from Intermediates of the Citric Acid Cycle and Other Major Pathways

Human beings can synthesize 11 of the basic set of 20 amino acids. These amino acids are called nonessential, in contrast with the essential amino acids, which must be supplied in the diet. The pathways for the synthesis of nonessential amino acids are quite simple. Glutamate dehydrogenase catalyzes the reductive amination of α-ketoglutarate to glutamate. A transamination reaction takes place in the synthesis of most amino acids. At this step, the chirality of the amino acid is established. Alanine and aspartate are synthesized by the transamination of pyruvate and oxaloacetate, respectively. Glutamine is synthesized from NH4+ and glutamate, and asparagine is synthesized similarly. Proline and arginine are derived from glutamate. Serine, formed from 3-phosphoglycerate, is the precursor of glycine and cysteine. Tyrosine is synthesized by the hydroxylation of phenylalanine, an essential amino acid. The pathways for the biosynthesis of essential amino acids are much more complex than those for the nonessential ones.

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Tetrahydrofolate, a carrier of activated one-carbon units, plays an important role in the metabolism of amino acids and nucleotides. This coenzyme carries one-carbon units at three oxidation states, which are interconvertible: most reduced—methyl; intermediate—methylene; and most oxidized—formyl, formimino, and methenyl. The major donor of activated methyl groups is S-adenosylmethionine, which is synthesized by the transfer of an adenosyl group from ATP to the sulfur atom of methionine. S-Adenosylhomocysteine is formed when the activated methyl group is transferred to an acceptor. It is hydrolyzed to adenosine and homocysteine, and the latter is then methylated to methionine to complete the activated methyl cycle.

24.3 Feedback Inhibition Regulates Amino Acid Biosynthesis

Most of the pathways of amino acid biosynthesis are regulated by feedback inhibition in which the committed step is allosterically inhibited by the final product. The regulation of branched pathways requires extensive interaction among the branches that includes both negative and positive regulation. The regulation of glutamine synthetase in E. coli is a striking demonstration of cumulative feedback inhibition and of control by a cascade of reversible covalent modifications.

24.4 Amino Acids Are Precursors of Many Biomolecules

Amino acids are precursors of a variety of biomolecules. Glutathione (γ-Glu-Cys-Gly) serves as a sulfhydryl buffer and detoxifying agent. Glutathione peroxidase, a selenoenzyme, catalyzes the reduction of hydrogen peroxide and organic peroxides by glutathione. Nitric oxide, a short-lived messenger, is formed from arginine. Porphyrins are synthesized from glycine and succinyl CoA, which condense to give δ-aminolevulinate. Two molecules of this intermediate become linked to form porphobilinogen. Four molecules of porphobilinogen combine to form a linear tetrapyrrole, which cyclizes to uroporphyrinogen III. Oxidation and side-chain modifications lead to the synthesis of protoporphyrin IX, which acquires an iron atom to form heme.