Biosynthesis of Amino Acids:- Serine, Glycine, and Cysteine Are Derived from 3-Phosphoglycerate
The major pathway for the formation of serine is the same in all organisms (Fig. 1). In the first step, the hydroxyl group of 3-phosphoglycerate is oxidized by a dehydrogenase (using NAD+) to yield 3-phosphohy droxypyruvate. Transamination from glutamate yields 3-phosphoserine, which is hydrolyzed to free serine by phosphoserine phosphatase. Serine (three carbons) is the precursor of glycine (two carbons) through removal of a carbon atom by serine hydroxymethyltransferase (Fig. 1). Tetrahydrofolate accepts the β carbon (C-3) of serine, which forms a methylene bridge between N-5 and N-10 to yield N5, N10-methylenetetrahydrofolate. The overall reaction, which is reversible, also requires pyridoxal phosphate. In the liver of vertebrates, glycine can be made by another route: the re verse of the reaction shown in Figure 18–20c, cat alyzed by glycine synthase (also called glycine cleavage enzyme):
CO2+NH+4+N5, N10-methylenetetrahydrofolate + NADH +H+ → glycine + tetrahydrofolate + NAD+
Plants and bacteria produce the reduced sulfur re quired for the synthesis of cysteine (and methionine, described later) from environmental sulfates; the path way is shown on the right side of Figure 22–13. Sulfate is activated in two steps to produce 3-phosphoadeno sine 5-phosphosulfate (PAPS), which undergoes an eight-electron reduction to sulfide. The sulfide is then used in formation of cysteine from serine in a two-step pathway. Mammals synthesize cysteine from two amino acids: methionine furnishes the sulfur atom and serine furnishes the carbon skeleton. Methionine is first con verted to S-adenosylmethionine (see Fig. 18–18), which can lose its methyl group to any of a number of acceptors to form S-adenosylhomocysteine (adoHcy). This demethylated product is hydrolyzed to free homocysteine, which undergoes a reaction with serine, catalyzed by cystathionine -synthase, to yield cystathionine. Finally, cystathionine -lyase, a PLP requiring enzyme, catalyzes removal of ammonia and cleavage of cystathionine to yield free cysteine.
FIGURE 1 Ornithine -aminotransferase reaction: a step in the mammalian pathway to proline. This enzyme is found in the mitochondrial matrix of most tissues. Although the equilibrium favors P5C formation, the reverse reaction is the only mammalian pathway for synthesis of ornithine (and thus arginine) when arginine levels are insufficient for protein synthesis.
FIGURE 22–12 Biosynthesis of serine from 3-phosphoglycerate and of glycine from serine in all organisms. Glycine is also made from CO2 and NH4 by the action of glycine synthase, with N5, N10-methylenetetrahydrofolate as methyl group donor (see text).
FIGURE 22–13 Biosynthesis of cysteine from serine in bacteria and plants. The origin of reduced sulfur is shown in the pathway on the right.
FIGURE 22–14 Biosynthesis of cysteine from homocysteine and serine in mammals. The homocysteine is formed from methionine, as described in the text.
