Y-Glutamyl cycle

The significance of the y-glutamyl cycle is not fully understood. However, the finding of a mentally retarded individual who excretes 25-50 g / day of 5-oxoproline in the urine (possibly because of a defective 5-oxoprolinase) suggests that the pathway is a very active one.111 A few persons deficient in y-glutamyl transpeptidase have been found. They excrete glutathione and have a variety of medical problems.109... 

Fig. 1. The y-glutamyl cycle. I, y-Glutamylcysteine synthetase II, glutathione synthetase III, y-glutamyl transpeptidase IV, y-glutamyl cyclotransferase V. peptidase. PCA = pyrrolidone carboxylic acid AA = amino acid.

Glutathione is independent of its reducing property as a y-glutamyl donor in the y-glutamyl cycle (fig. 22.15). Of particular significance is the fact that cells exhibiting the activities of the cycle contain substantial amounts of y-... 

The y-glutamyl cycle enzymes are found in those tissues where glutathione transport into cells is an important function. Whereas glutathione is exported by most cells, it is... 

Gly) formed in the reaction is transported by an uncharacterized transport system (3) and cleaved by an intracellular protease (4) or cleaved by a membrane-bound protease and the free amino acids transported. The y-glutamyl cycle enzymes are found in those tissues for which the transport of glutathione into cells is an important function. This includes liver and kidney cells in animals. 

The same amino acid, named as 5-oxoproline, is an intermediate in the y-glutamyl cycle. The name pyro-glutamate suggests formation involving dehydration via heat (fire) from glutamate. 

Kurelec, B. Rijavec, M. (1976). Occurrence of y-glutamyl cycle in some parasitic helminths. In Biochemistry of parasites and host-parasite relationships, ed. H. Van den Bossche, pp. 101-7. North-Holland Publishing Co. The Netherlands. 

A different mechanism for translocation of amino acids in some cells is employed in the y-glutamyl cycle (Figure 17.2). Its operation requires six enzymes (one membrane-bound, the rest cytosolic), glutathione (GSH y-glutamylcysteinylglycine present in all tissue cells). 

Fig. 1 y-Glutamyl cycle. AA amino acid, y-GGT y-glutamyl transpeptidase... 

Transport of amino acids into cells is mediated by specific membrane-bound transport proteins, several of which have been identified in mammalian cells. They differ in their specificity for the types of amino acids transported and in whether the transport process is linked to the movement of Na+ across the plasma membrane. (Recall that the gradient created by the active transport of Na+ can move molecules across membrane. Na+-dependent amino acid transport is similar to that observed in the glucose transport process illustrated in Figure 11.28.) For example, several Na+-dependent transport systems have been identified within the lumenal plasma membrane of enterocytes. Na+-independent transport systems are responsible for transporting amino acids across the portion of enterocyte plasma membrane in contact with blood vessels. The y-glutamyl cycle (Section 14.3) is believed to assist in transporting some amino acids into specific tissues (i.e., brain, intestine, and kidney). 

The y-glutamyl cycle provides for the active transport of several amino acids, especially cysteine and methionine, as well as GSH itself. Some researchers consider the amino acid transport function of GSH controversial. An alternative... 

Larrson A, Anderson ME. Glutathione synthetase deficiency and other disorders of the y-glutamyl cycle. In Scriver CR, Beaudet AL, Valle D, Sly WS, et al., eds. The Metabolic and Molecular Bases of Inherited Disease, vol II, 8th Ed. New York McGraw-Hill, 2001 2205-2216. 

G. is involved in the biosynthesis of "glutathione and numerous y-glutamyl compounds and acts as an amino acid carrier in the degradation steps of the y-glutamyl cycle. In the CNS G. is an inhibitory neuro-... 

A number of lines of evidence indicates that the -y-glutamyl cycle also operates in plants. In Chlorella sulfur is incorporated into GSH at a rate approximately ninefold faster than is accounted for by the net accumulation of this amino acid (Fig. 1). The reactions of the -y-glutamyl cycle are the only ones presently known which could account for this turnover. In addition to the enzymes of GSH synthesis, two other enzymes of the -y-glutamyl cycle are known to occur in plants. -y-Glutamyltransferase (E.C. 2.3.2.2.) has been detected in many plants (Thompson et al., 1964) and was purified from kidney beans (Goore and Thompson, 1%7). The -y-glutamyldipeptide products... 

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