Principles of Biochemistry, Volume 2 - A. Lehninger 1985

Bioenergetics and Metabolism
Biosynthesis of Amino Acids and Nucleotides
Serine serves as a precursor to glycine

Since Serine is a precursor of Glycine, we discuss the biosynthetic pathways of both Amino Acids together here. The main pathway for serine formation in animal Tissues (Fig. 22-6) begins with 3-phosphoglycerate, an intermediate of Glycolysis. In the first step, the α-hydroxyl group of 3-phosphoglycerate is oxidized by NAD⁺ to yield 3-phosphohydroxypyruvate. The latter undergoes Transamination with glutamate to form 3-phosphoserine. Finally, 3-phosphoserine undergoes Hydrolysis catalyzed by phosphoserine phosphatase, which yields free serine.

Glycine, whose molecule contains two carbon atoms, is formed from the three-carbon amino acid serine by the removal of a single carbon atom—specifically the β-carbon atom, i.e., C-3 (Fig. 22-6). This reaction is catalyzed by an enzyme that utilizes tetrahydrofolate as a coenzyme, which is the active form of the vitamin known as Folic acid (Sec. 10.10). Tetrahydrofolate acts as an acceptor for the β-carbon atom of serine during glycine formation. The carbon atom cleaved from serine forms a methylene bridge (Sec. 19.4) between the nitrogen atoms at positions 5 and 10 of tetrahydrofolate, yielding N⁵,N¹⁰-methylenetetrahydrofolate (Fig. 22-7). The reaction forming glycine from serine is reversible.

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N⁵,N¹⁰-Methylenetetrahydrofolate belongs to a family of Coenzymes that are derivatives of folic acid; like S-adenosylmethionine and coenzyme B₁₂, these folic acid derivatives function as carriers of various one-carbon groups (Sec. 10.10). The one-carbon fragment cleaved from serine with the participation of tetrahydrofolate can be transferred to various acceptor molecules.

In vertebrate Liver, glycine can be formed via an alternative pathway (Sec. 19.4) involving the enzyme glycine synthase.

Fig. 22-6. Biosynthesis of serine from 3-phosphoglycerate and the subsequent conversion of serine into glycine. Glycine can also be formed from CO₂ + NH₃ through the action of glycine synthase, which utilizes N⁵,N¹⁰-methylenetetrahydrofolate as a methyl group donor (see text).

Fig. 22-7. Structure of N⁵,N¹⁰-methylenetetrahydrofolate. The transferable methylene group is shown against a red Background (see Fig. 10-12).