Biochemistry of Amino Acids - A. Meister 1961

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

Several years ago, Glycine was found to be the source of nitrogen in hemin [145]. Subsequent studies showed that the α-carbon atom of glycine (but not the carboxyl carbon) is also utilized in hemin synthesis [146, 147]. The analysis of protoporphyrin degradation products has largely elucidated the Water/144.html">Origin of the various structural parts of this molecule [148–150]. It was established that the four carbon atoms of the methane bridges and the four carbon atoms in the pyrrole rings originate from the α-carbon atoms of glycine. The distribution of the isotopic label in protoporphyrin formed from labeled intermediates of The Citric Acid Cycle was also investigated [150, 151].

Shemin and coworkers [152–155] found that the α-carbon atoms of glycine are used equally for the Synthesis of the pyrrole rings and The formation of the methine bridges. They concluded that these carbon atoms of the protoporphyrin molecule derive from the same glycine derivative. According to Shemin's scheme, "active succinate"¹ condenses with the α-carbon atom of glycine to form α-amino-β-ketoadipic acid, which is then decarboxylated and converted into δ-aminolevulinic acid. The latter can serve as a porphyrin precursor or undergo deamination to yield α-ketoglutaric acid semialdehyde, which in turn can be converted into succinic acid and a single-carbon unit utilized for the Synthesis of Purines, Serine, and the Methionine methyl group. Upon administration of 5-C¹⁴-δ-aminolevulinic acid to ducks, the label was recovered in the ureido groups of purines, the β-carbon atom of serine, and the methyl group of methionine.

During porphyrin synthesis in duck erythrocytes, δ-aminolevulinic acid [155–157] replaces "active succinate" and glycine [152]. Furthermore, it was found that The addition of unlabeled δ-aminolevulinic acid to a system synthesizing hemin from radioactive glycine and succinic acid reduces the radioactivity of the resulting hemin. In experiments using δ-aminolevulinic acid labeled with N¹⁵ or C¹⁴ at the 5-position, intensive incorporation of isotopes into hemin was observed. Shemin and Russell [152] suggested that two molecules of δ-aminolevulinic acid condense in this process to form a compound that serves as the precursor of the porphyrin pyrrole rings (see scheme on p. 324).

It was later found that Cell-free extracts of duck erythrocytes catalyze the formation of protoporphyrin from δ-aminolevulinic acid, but fail to produce it from glycine and succinic acid [153]. Thus, the system involved in the Condensation of succinic acid and glycine is disrupted upon cell lysis. Shemin and coworkers' observations have been confirmed by other researchers [156, 158].

¹ It is now known that the active derivative of succinic acid involved in porphyrin synthesis is succinyl-CoA. — Ed. note.

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(Asterisks indicate the carbon atoms of the succinic acid carboxyl groups, and dots denote the α-carbon atoms of glycine.)

The putative condensation product of two δ-aminolevulinic acid molecules is identical to porphobilinogen [158–162], which is excreted in the urine of patients suffering from acute porphyria [159]. The subsequent stages of porphobilinogen conversion into Porphyrins are not yet fully understood [163, 164]¹.