Cysteine catabolism

Taurine (H3N CH2CH2S03 ) is formed as a product of cysteine catabolism and also arises from the oxidation of cyste-amine, which is produced during coenzyme-A degradation. It was given the name taurine because it was first isolated from the bile of the ox, Bos taurus. 

A quantitatively important pathway of cysteine catabolism in animals is oxidation to cysteine sulfinate (Fig. 24-25, reaction z),450 a two-step hydroxyl-ation requiring 02, NADPH or NADH, and Fe2+. Cysteine sulfinic acid can be further oxidized to cyste-ic acid (cysteine sulfonate),454 which can be decarbox-ylated to taurine. The latter is a component of bile salts (Fig. 22-16) and is one of the most abundant free amino acids in human tissues 455-457 Its concentration is high in excitable tissues, and it may be a neurotransmitter (Chapter 30). Taurine may have a special function in retinal photoreceptor cells. It is an essential dietary amino acid for cats, who may die of heart failure in its absence,458 and under some conditions for humans.459 In many marine invertebrates, teleosts, and amphibians taurine serves as a regulator of osmotic pressure, its concentration decreasing in fresh water and increasing in salt water. A similar role has been suggested for taurine in mammalian hearts. A chronically low concentration of Na+ leads to increased taurine.460 Taurine can be reduced to isethionic acid... 

Taurine was discovered in 1827 in ox hUe, where it is conjugated with the bile acids. It was later shown to be a major excretory product of the sulfur amino acids methionine and cysteine. Until about 1976, it was assumed that it was a metabolic end-product whose only function was the conjugation of bile acids. In the rat, taurine synthesis accounts for 70% to 85% of total cysteine catabolism. 

Sulfite oxidase catalyzes one of the final stops in the oxidation of the sulfur amino acids. The catabolism of methionine can result in the appearance of its sulfur atom in cysteine, as shown in Chapter 8. Cysteine can be oxidized to cysteine sulfonate, as shciwn in the section on taurine in Chapter 2, and then degraded to pyruvate. Daily, an average of 25 mmol of sulfite is produced in the body. This amount is large compared with the dally intake of fo< sulfite, which is about 2.5 mmol- The point at which sulfite oxidase occurs in the cysteine catabolic pathway is shown in Figure 10,53, Sulfate (SO ") is required for the synthesis of su I fated polypeptides and polysaccharides. It is thought that sulfate is not required in the dict-... 

FIGURE 10,53 Cysteine catabolic pathway and sulfate formation. 

The major end products of cysteine catabolism in humans are inorganic sulfate, taurine, and pyruvate. Taurine is a /1-amino acid that has a sulfonic acid instead of a... 

The sulfur atom of methionine becomes the sulfur atom of cysteine. The sulfate generated in cysteine catabolism is excreted or used in several biosynthetic or catabolic pathways. The transulfuration and methylation pathways are intimately related. 

Cysteine catabolism. Several pathways of cysteine catabolism are presented, including the formation of taurine and inorganic sulfate. 

Fig. 3. Regulation of the bound pathway for the assimilation of sulfate into cysteine and associated processes. Carrier refers to an endogenous thiol of uncertain identity in higher plants. Enzymes associated with the sulfate assimilation pathway and the synthesis of O-acetylseiine are (1) high-ailinity sulfate uptake mechanism, (2) ATP-sulfurylase, (3) adenosine S -phosphosulfate (APS) sulfotransferase, (4) organic thiosulfate reductase, (5) cysteine synthase, and (6) serine transacetylase. Cysteine sulfhydrase (7), an enzyme of cysteine catabolism, and nitrate reductase (8), the first enzyme of the nitrate assimilation pathway, are also shown. Inhibitory control of the pathways is shown by discontinuous lines (----) and enhancement by continuous lines (------).

Other mechanisms of cysteine catabolism have been reported in animals. One such mechanism involves the metaboUsm of cysteine to mercaptopyruvate in a reaction involving amino acid oxidase [Eq. (5)] or aminotransferase activity [Eq. (6)] ... 

The production of H2S from exogenous L-cysteine and D-cysteine, which is largely light independent, is discussed under cysteine catabolism in Section VI. 

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). 

Figure 30-8. Catabolism of i-cysteine via the cysteine sulfinate pathway (top) and by the 3-mercaptopy-ruvate pathway (bottom).

Hexachlorobutadiene is a nephrotoxic industrial chemical, damaging the pars recta of the proximal tubule. Initial conjugation with GSH is necessary, followed by biliary secretion and catabolism resulting in a cysteine conjugate. The conjugate is reabsorbed and transported to the kidney where it can be concentrated and becomes a substrate for the enzyme p-lyase. This metabolizes it into a reactive thiol, which may react with proteins and other critical macro molecules with mitochondria as the ultimate target. The kidney is sensitive because the metabolite is concentrated by active uptake processes (e.g., OAT 1), which reabsorb the metabolite into the tubular cells. 

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... 

Bound NAD+ is also present in S-adenosylhomo-cysteine hydrolase,119 120 which catalyzes the irreversible reaction of Eq. 15-14. Transient oxidation at the 3 position of the ribose ring facilitates the reaction. The reader can doubtless deduce the function that has been established for the bound NAD+ in this enzyme. However, the role of NAD in the urocanase reaction (Eq. 15-15) is puzzling. This reaction, which is the second step in the catabolism of histidine, following Eq. 14-44, appears simple. However, there is no obvious... 

Synthesis and Catabolism of Pro line 1406. .. G. Cysteine and Sulfur Metabolism... 

Synthesis of Arginine and Ornithine and the 1407 1. Synthesis and Catabolism of Cysteine... 

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... 

Figure 24-25 Pathways of biosynthesis (green arrows) and catabolism of cysteine as well as other aspects of sulfur metabolism. Solid arrows are major biosynthetic pathways. The dashed arrows represent more specialized pathways they also show processes occurring in the animal body to convert methionine to cysteine and to degrade the latter.

The subsequent cleavage of cystathionine to yield cysteine, a-ketobutyrate and NH4+ is catalyzed by y-cystathionase, a pyridoxal-phosphate-containing enzyme. This transsulfura-tion pathway is one of the routes used for methionine catabolism. 

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