Cysteine transamination

Alanine. Transamination of alanine forms pyruvate. Perhaps for the reason advanced under glutamate and aspartate catabolism, there is no known metabolic defect of alanine catabolism. Cysteine. Cystine is first reduced to cysteine by cystine reductase (Figure 30-7). Two different pathways then convert cysteine to pyruvate (Figure 30-8). 

The same group have used the enzyme combination employed in the aspartate deracemization cited above to deracemize 2-naphthylalanine, hut have made use of an interesting innovation introduced by Helaine et al to pull over the poised equilibrium of the transamination reaction. Cysteine sulphinic acid was used as the amino donor in the transamination. The oxoacid product spontaneously decomposes in to pyruvic acid and SO2 (Scheme 3). 

Evidence was also provided that Insoluble residues may be produced from GSH conjugates via cysteine conjugate or thiol Intermediates. These studies also suggested that certain reactions should be studied in greater detail to assess their importance in pesticide metabolism l.e., the C-S lyase reaction, the methyl transferase reaction, and the transamination reaction. 

The carbon skeletons of six amino acids are converted in whole or in part to pyruvate. The pyruvate can then be converted to either acetyl-CoA (a ketone body precursor) or oxaloacetate (a precursor for gluconeogenesis). Thus amino acids catabolized to pyruvate are both ke-togenic and glucogenic. The six are alanine, tryptophan, cysteine, serine, glycine, and threonine (Fig. 18-19). Alanine yields pyruvate directly on transamination with... 

When present in excess methionine is toxic and must be removed. Transamination to the corresponding 2-oxoacid (Fig. 24-16, step c) occurs in both animals and plants. Oxidative decarboxylation of this oxoacid initiates a major catabolic pathway,305 which probably involves (3 oxidation of the resulting acyl-CoA. In bacteria another catabolic reaction of methionine is y-elimination of methanethiol and deamination to 2-oxobutyrate (reaction d, Fig. 24-16 Fig. 14-7).306 Conversion to homocysteine, via the transmethylation pathway, is also a major catabolic route which is especially important because of the toxicity of excess homocysteine. A hereditary deficiency of cystathionine (3-synthase is associated with greatly elevated homocysteine concentrations in blood and urine and often disastrous early cardiovascular disease.299,307 309b About 5-7% of the general population has an increased level of homocysteine and is also at increased risk of artery disease. An adequate intake of vitamin B6 and especially of folic acid, which is needed for recycling of homocysteine to methionine, is helpful. However, if methionine is in excess it must be removed via the previously discussed transsulfuration pathway (Fig. 24-16, steps h and z ).310 The products are cysteine and 2-oxobutyrate. The latter can be oxidatively decarboxylated to propionyl-CoA and further metabolized, or it can be converted into leucine (Fig. 24-17) and cysteine may be converted to glutathione.2993... 

Another route of metabolism for cysteine sulfinic acid is transamination to 3-sulfinylpyruvate, a compound that undergoes ready loss of S02 in a reaction analogous to the decarboxylation of oxaloacetate (reaction o, Fig. 24-25). This probably represents one of the major routes by which sulfur is removed from organic compounds in the animal body. However, before being excreted the sulfite must be oxidized to sulfate by the Mo-containing sulfite oxidase. The essentiality of sulfite oxidase is evidenced by the severe neurological defect observed in its absence (Chapter 16). 

Cysteine can undergo the Strecker degradation, transamination, and -elimination, as shown by Tressl et al.247 using [1- or 6-13C]glucose (equimolar aqueous solution, 160 °C, 1.5 h). 2-Furylmethanethiol (T 0.005 ppb), very important in providing the aroma of roasted coffee and roasted meat, is formed as shown in Scheme 5.14 from [l-13C]glucose via the 3-deoxy-l,2-dicarbonyl, which loses... 

It is not known to what extent taurine may be a dietary essential for human beings. There is little cysteine sulfinic acid decarboxylase activity in the human liver and, like the cat, loading doses of methionine and cysteine do not result in any significant increase in plasma taurine. This may be because cysteine sulfinic acid can also undergo transamination to /3-sulfhydryl pyruvate, which then loses sulfur dioxide nonenzymically to form pyruvate, thus regulating the amount of taurine that is formed from cysteine. There is no evidence of the development of any taurine deficiency disease under normal conditions. 

Pyruvate is the entry point of the three-carbon amino acids—alanine, serine, and cysteine—into the metabolic mainstream (Figure 23.22). The transamination of alanine directly yields pyruvate. 

It is apparent that methodological problems limit the usefulness of the kinetic approach to studying mechanisms. However, data of an entirely different nature argue against a sequential model for the aspartate transporter. Studies of the metabolism of cysteine sulfinic acid show that it is transported by the glutamate/aspartate transporter and that it transaminates with a-ketoglutarate or oxalacetate to yield glutamate or aspartate and jS-sulfinyl pyruvate, which spontaneously hydrolyzes into sulfite and pyruvate [148,149]. 

Cysteine derives its carbon and nitrogen from serine. The essential amino acid methionine supplies the sulfur, d. Alanine can be derived by transamination of pyruvate. 

Xenobiotics and Cysteine Conjugates That Are Excreted as Transaminated Metabolites... 

Sulfoxidation. Sulfoxidation Is common in sulfur biochemistry (43,44), and has been observed with many of the transamination products listed in Table III, with mercapturic acids (45,46,47) and cysteine conjugates (12). Sulfoxidation is also common with the methylthio-containing metabolites produced from cysteine conjugates (see "Thiol Formation" below). Sulfoxidation increases the polarity of compounds and therefore affects their excretability. 

Cysteine. In animals, cysteine is converted to pyruvate by several pathways. In the principal pathway, the conversion occurs in three steps. Initially, cysteine is oxidized to cysteine sulfate. Pyruvate is produced after a transamination and a desulfuration reaction. 

Fig. 39.1. Overview of the synthesis of the nonessential amino acids. The carbons of 10 amino acids may be produced from glucose through intermediates of glycolysis or the TCA cycle. The 11th nonessential amino acid, tyrosine, is synthesized by hydroxylation of the essential amino acid phenylalanine. Only the sulfur of cysteine comes from the essential amino acid methionine its carbons and nitrogen come from serine. Transamination (TA) reactions involve pyridoxal phosphate (PLP) and another amino acid/a-keto acid pair.

In addition to transamination reactions, one-carbon transfer reactions occur frequently in amino acid biosynthesis. A good example of a one-carbon transfer can be found in the reactions that produce the amino acids of the serine family. This family also includes glycine and cysteine. Serine and glycine themselves are frequently precursors in other biosynthetic pathways. A discussion of the synthesis of cysteine will give us some insight into the metabolism of sulfur, as well as that of nitrogen. 

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