Amino acid degradation homocysteine

Vitamin Bjj (8.50, cobalamin) is an extremely complex molecule consisting of a corrin ring system similar to heme. The central metal atom is cobalt, coordinated with a ribofuranosyl-dimethylbenzimidazole. Vitamin Bjj occurs in liver, but is also produced by many bacteria and is therefore obtained commercially by fermentation. The vitamin is a catalyst for the rearrangement of methylmalonyl-CoA to the succinyl derivative in the degradation of some amino acids and the oxidation of fatty acids with an odd number of carbon atoms. It is also necessary for the methylation of homocysteine to methionine. 

There are two pyridoxal phosphate-requiring enzymes in the homocysteine degradation pathway, which are associated with genetic diseases. In homo-cystinuria, cystathionine synthase is defective, and large amounts of homocystine are excreted in the urine. Some homocystinurics respond to the administration of large doses of vitamin B6. In cystathioninuria, cystathionase is either defective or absent. These patients excrete cystathionine in the urine. Cystathionase is often underactive in the newborns with immature livers, and cysteine and cystine become essential amino acids. Human milk protein is especially rich in cysteine, presumably to prepare the newborn for such a contingency. 

The mammalian synthesis of methionine is more complex and requires cobalamin, a coenzyme form of vitamin B12. Note that because methionine is an essential amino acid, it must be supplied in the diet methionine that is used for methylation (Fig. 15-20) is degraded to homocysteine, and this is remethylated to give methionine. These reactions merely recycle methionine and do not constitute a means of net synthesis. 

The conversion of methionine to homocysteine and homocysteine to cysteine is the major degradative route for these two amino acids. Because this is the only degradative route for homocysteine, vitamin B6 deficiency or congenital cystathi-none (3-synthase deficiency can result in homocystinemia, which is associated with cardiovascular disease. 

The amino acid homocysteine 148 is obtained on treatment of cystathione 99 with the enzyme / -cystathionase (EC 4.4.1.8). Chang and Walsh (128) used the samples of (4R)- and (4S)-[4- Hi]cystathione 99a, prepared as in Scheme 37, in this reaction and degraded the samples of homocysteine produced to labeled homoserinelactones. This indicated that, as expected, the chirally labeled center was not disturbed in the reaction. 

In vitamin B22 deficiency methyltetrahydrofolate cannot donate its methyl group to homocysteine to regenerate methionine. Because the synthesis of methyltetrahydrofolate is irreversible (text, p. 675), the cell s tetrahydrofolate ultimately will be converted into this form. No formyl or methylene tetrahydrofolate will be left for nucleotide synthesis. Pernicious anemia illustrates the intimate connection between amino acid metabolism and nucleotide metabolism. The metabolism of fatty acids that have odd numbers of carbons also will be affected because methylmalonyl-CoA mutase requires vitamin B22 for the production of succinyl-CoA. A further connection is that methylmalonyl-CoA mutase also is involved in the degradation of valine and isoleucine. 

Incorporation of the amino acids L-2,4-diaminobutyric acid (DAB) and homocysteine (HCY) into a PEA backbone was investigated with the aim of imparting stimuli-responsive degradation properties. Studies on model compounds revealed that the pendant y-amine or y-thiol of DAB and HCY esters experimented intramolecular cyclizalions at a much more rapid rate than background ester hydrolysis. Thus, stimuli-induced cyclization reactions (i.e., after deprotection of pendant groups by acids or reducing agents) were effective to cleave ester... 

When administered to subjects of the metabolic disease cystinuria, cysteine, homocysteine and methionine are excreted largely as additional cystine whereas administered cystine, homocystine and glutathione are almost completely oxidised. From these observations it is concluded that cystine can be metabolised without previous reduction to cysteine, and that glutathione can be meta-bobsed without previous hydrolysis, indicating that the metabolic history of an amino acid may depend on whether it is free or combined. Methionine, previous to its conversion into cysteine is demethylated to form homocysteine, which may undergo condensation to homocystine or degradation to simpler products. 

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