Biochemistry - The Chemical Reactions of Living Cells, Volume 3 - D. Metzler 1980

Metabolism of Nitrogenous Compounds
Incorporation of NH3 into Amino Acids and Proteins
Uptake of Amino Acids by Cells

While autotrophic Cells can synthesize all necessary Amino Acids themselves (via the pathways described in subsequent sections), other cells must obtain many amino acids preformed. Humans and other higher animals require A number of Essential Amino Acids in their diet. Furthermore, cells of a specific tissue can take up amino acids synthesized in another tissue.

We have already briefly mentioned The Active Transport systems utilized by Bacteria for amino acid uptake (Chap. 5, Sec. B, 2). Another fascinating active transport system, the $\gamma$-glutamyl cycle [27], operates in mammalian cells. This cycle relies on the utilization of the $\gamma$-carboxyl group of glutamate—specifically, the carboxyl group involved in the amide bond with ammonia in glutamine. During Amino Acid Transport, Glutathione serves as the donor of the activated $\gamma$-glutamyl group (Supplement 7-F); The amino acid to be transported undergoes a transpeptidation reaction [Eq. (14-14), step a], presumably located within The Cell membrane. The resulting $\gamma$-glutamyl amino acid is then translocated into the Cytoplasm, where the free amino acid is released by displacement with a free $\alpha$-amino group [Eq. (14-14), step b]. Notably, the inherent tendency of the 5-carbon chain of glutamate to cyclize acts as the driving force for releasing the bound amino acid. The resulting cyclic product, 5-oxoproline, is subsequently cleaved in an ATP-requiring reaction [Eq. (14-14), step c] [28].

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The cysteinyl-Glycine formed during the initial transpeptidation stage [Eq. (14-14)] is hydrolyzed by a peptidase. Subsequently, glutathione is regenerated via two ATP-dependent steps, as illustrated in the pathway diagram.

The exact physiological Significance of the $\gamma$-glutamyl cycle remains to be fully elucidated. However, an investigation of a case involving mental retardation revealed that the patient excreted 25–50 g of 5-oxoproline per day in the urine (likely due to a defect in 5-oxoprolinase), which indicates an extraordinarily high rate of flux through the $\gamma$-glutamyl cycle [28].