Biochemistry of Amino Acids - A. Majster 1961

Intermediary Metabolism of Amino Acids
Glycine, Serine, and Sarcosine
Sarcosine

Rat experiments demonstrating that sarcosine is an intermediate in METABOLISM have revealed a new dimension in the complex problem of single-carbon residue metabolism. Horner and MacKenzie [220] observed significant label incorporation into urinary sarcosine following the administration of sarcosine along with Methionine and betaine labeled with C¹⁴ in the methyl group. In Liver preparations, methyl-labeled sarcosine was converted to formaldehyde and formic acid containing the label [221]. These compounds were also detected in animal urine after administration of C¹⁴-sarcosine, with a substantial amount of the labeled carbon excreted as CO₂. In vitro experiments revealed appreciable amounts of the isotope in Glycine and Serine. It has been established that dimethylglycine is a precursor of sarcosine and is oxidized to sarcosine and formaldehyde by a specific oxidase distinct from sarcosine oxidase. Sarcosine oxidase, found in the liver, converts sarcosine to formaldehyde and glycine. Thus, through the sequential action of discrete oxidative Enzymes, both methyl groups of dimethylglycine—known to be formed during betaine demethylation (p. 371)—can be converted to formaldehyde. The resulting glycine can condense with single-carbon fragments generated in the same oxidative pathway to form serine. The conversion of Choline to betaine will be discussed below (p. 371). The aforementioned reactions are summarized in the following scheme [178]:

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Other reactions of this cycle, which generally represents The Mechanism of methyl group oxidation, can also be considered established. Stetten [222] observed the conversion of N¹⁵-serine to ethanolamine, suggesting that serine is converted to ethanolamine via decarboxylation. Evidence indicates that in the rat, serine labeled at the ß-carbon atom is converted to ethanolamine found in the liver lipid fraction [172, 210]. However, following the administration of glycine labeled at the a-carbon, no appreciable label incorporation into ethanolamine was observed, indicating that glycine reduction does not play a significant role in ethanolamine formation. It is also known that in rats, N-methyl- and N-dimethylethanolamine, alongside ethanolamine, serve as precursors for choline. Through this cycle, the ß-carbon atom of serine can be converted into the carbon atom of the carboxyl group of glycine and serine itself, and consequently into CO₂. The Nature of the active single-carbon fragments generated in these reactions remains unknown, although, as noted above, it can be hypothesized that Folic acid derivatives are involved in these processes. Much of the data is consistent with the reactions shown in the scheme, but it is evident that alternative pathways for Serine and Glycine metabolism also exist. For instance, it is known that the a-carbon atom of glycine is converted via formic acid into the ß-carbon atom of serine [169]. It is quite probable that the methyl group of methionine may be oxidized via other pathways as well (see p. 375).