Cysteine transaminase

Jones TW, Chen Q, Schaeffer V, et al. 1988. Immunohistochemical localization of glutamine transaminase K, a rat kidney cysteine conjugate p-lyase, and the relationship to the segment specificity of cysteine conjugate nephrotoxicity. Mai Pharm 34 621-627. 

The fermentation methods used to prepare L-phenylalanine, threonine, lysine, and cysteine are discussed in detail in Chapter 3. The adaptation of these methods to prepare unnatural amino acids, such as the use of transaminases, is also discussed in that chapter. One of the large-scale amino acids, L-glumatic acid, which is often sold as its monosodium salt, is not covered because its preparation by fermentation is long established.3... 

A number of amino acids, like alanine, leucine, tyrosine, aspartic acid, cystein and arginine react with a-ketoacids and transfer their a-amino group to the a-carb-on of the a-keto acids. These reactions are catalysed by the enzyme called transaminase or aminotransferase. For example, transfer of the amino group of aspartic acid (14) to a-ketoglutaric acid (23) gives glutamic acid (16) and oxaloacetic acid (24). 

Lin C-T, Li J-Z, Wu J-Y (1983) Immunocytochemical localization of L-glutamate decarboxylase, gamma-aminobutyric acid transaminase, cysteine sulfinic acid decarboxylase, aspartate aminotransferase and somatostatin in rat retina. Brain Res 270 273-283. 

Cysteine was also an elTective inactivator in vitro] the closely related compound penicillamine (/3,j8-dimethylcysteine) is slightly more reactive - . Penicillamine inhibits the transaminases of rat liver and the glutamic acid decarboxylase of mouse brain . The formation of thiazolidine derivatives by reaction of cysteine or penicillamine with pyridoxal phosphate proceeds... 

Boettcher, B., and Martinez-Carrion, M. (1975). Biochem. Biophys. Res. Comm. 64, 28. Glutamate Aspartate Transaminase Modified at Cysteine 390 with Enriched Carbon-13 Cyanide. 

Acetaminophen (paracetamol) is a commonly used analgesic which is hepatotoxic at high doses in humans and in laboratory animals. Toxicity is believed to be mediated by the reactive metabolite N-acetyl-p-benzoquinone imine which binds to protein thiols as 3-(cystein-S-yl)acetaminophen adducts. Ultrasensitive immimoassays for 3-(with parallel elevations in serum adducts and serum levels of the liver-specific transaminase ALT. This suggested that the serum adducts were of hepatic origin and could be monitored as a biomarker of acetaminophen toxicity. Analysis of serum samples from acetaminophen overdose patients demonstrated a positive correlation between immunochemically detectable serum adducts and hepatotoxicity. 

Reaction 1 is a transamination reaction to form mercaptopyruvate. A transaminase in higher plants which will utilize cysteine or cystine as the amino donor has never been reported. In fact Forest and Wightman (1972) showed that cystine was not an amino donor to any keto acid tested with extracts of bush bean cotyledons or seedlings. It was unique in this respect in that the only other protein amino acids which acted in this manner were the two imino acids proline and hydroxyproline. 

Although not completely known, the amino acid sequence of the rabbit muscle aldolase subunit is largely elucidated. (A more detailed description on protein structure appears in the chapter on inborn errors of metabolism.) The molecule contains 364 amino acids with a proline NH2-terminal, a tyrosine in the COOH-terminal position, and 8 cysteine residues. A critical residue is the lysine 221 which is believed to form a Schiff base with dihydroxyacetone phosphate. (The role of Schiff bases in enzymic reactions is discussed in more detail in the section devoted to transaminases.) In the model proposed by Lai und Horecker [51], this lysine is near the center of the molecule. If one follows the contour of the molecule from this critical residue 221, which must be at the active center, toward the tyrosine carboxy terminal, three SH groups are well exposed on the surface of the molecule. They occupy positions 193, 171, and 143. 

The metabolic pathway of 7 to 4 in rats was proposed. The metabolic reactions were 1) transamination of amino group of cysteine 2) reduction of ketone group of pyruvic acid. Above-mentioned step 1) and 2) were catalyzed by cysteine conjugate transaminase and 3-mercaptopyruvic acid 5-conjugate reductase, respectively. Proposed metabolic pathway of 7 to 4 in rat (in vitro) are shown in Figure 4. 

In animal tissues cysteinesulfinic acid can undergo transamination, decarboxylation, and oxidation. In certain strains of Proteus vulgaris an alternative oxidation and transamination operate simultaneously 18). It was shown by Cohen 19) and by Kearney and Singer 18) that both in animal and microbial systems the transamination of cysteine sulfinate catalyzed by glutamate-aspartate transaminase proceeds as follows ... 

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