BIOCHEMISTRY - L. Stryer - 1984

VOLUME 2

PART III. BIOSYNTHESIS OF MACROMOLECULAR PRECURSORS

CHAPTER 21. BIOSYNTHESIS OF AMINO ACIDS AND HEME

Summary

Microorganisms use ATP and a powerful reductant to reduce N₂ to NН₄. Ammonium salts are then used by higher organisms to synthesize Amino Acids, NUCLEOTIDES, and other molecules. The major entry points through which NН²₄ is introduced into Intermediary METABOLISM are glutamine, glutamate, and carbamoyl phosphate. The Human Body can synthesize only about half of the standard set of twenty amino acids. These Amino acids are called nonessential, in contrast to the essential ones, which must be supplied in the diet. The biosynthetic pathways for nonessential amino acids are very simple. Glutamate dehydrogenase catalyzes the reductive amination of α-ketoglutarate to form glutamate. Alanine and aspartate are synthesized by Transamination of Pyruvate and oxaloacetate, respectively. Glutamine is synthesized from NH₄⁺ and glutamate, and asparagine is formed in a similar manner. Proline is synthesized from glutamate. Serine, formed from 3-phosphoglycerate, is the precursor of Glycine and Cysteine. Tyrosine is synthesized by hydroxylation of the essential amino acid phenylalanine. The biosynthetic pathways for Essential Amino Acids are much more complex than those for nonessential ones. These pathways are mostly regulated by feedback inhibition, where the committed step is allosterically inhibited by the end product. The regulation of E. coli Glutamine Synthetase is a striking example of cumulative Feedback inhibition and control via a cascade of reversible covalent modifications.

Tetrahydrofolate is a carrier of activated one-carbon units; it plays an important role in the metabolism of Amino Acids and nucleotides. This coenzyme carries one-carbon fragments at various oxidation states that are interconvertible: the most reduced form is the methyl group; the most oxidized are the formyl, formimino, and methenyl groups; and the intermediate oxidation state is the methylene group. The primary donor of activated methyl groups is S-adenosylmethionine, which is synthesized by The transfer of the adenosyl group of ATP to the sulfur atom of Methionine.

S-adenosylhomocysteine is formed As a result of the transfer of the activated methyl group to an acceptor. It is cleaved into adenosine and homocysteine, which is then methylated to form methionine, thereby completing the activated methyl cycle.

Amino acids are precursors of many different molecules. Porphyrins are synthesized from glycine and succinyl-CoA, which condense to form δ-aminolevulinate. Molecules of this intermediate condense with each other to form porphobilinogen. Four molecules of porphobilinogen combine to form a linear tetrapyrrole, which cyclizes to yield uroporphyrinogen III. Oxidation and side-chain modifications lead to The formation of protoporphyrin IX, which binds an iron atom to become heme. δ-Aminolevulinate synthase, The enzyme catalyzing the committed step of this biosynthetic pathway, is feedback-inhibited by heme.