Methionine transamination

Pyridoxamine phosphate serves as a coenzyme of transaminases, e.g., lysyl oxidase (collagen biosynthesis), serine hydroxymethyl transferase (Cl-metabolism), S-aminolevulinate synthase (porphyrin biosynthesis), glycogen phosphoiylase (mobilization of glycogen), aspartate aminotransferase (transamination), alanine aminotransferase (transamination), kynureninase (biosynthesis of niacin), glutamate decarboxylase (biosynthesis of GABA), tyrosine decarboxylase (biosynthesis of tyramine), serine dehydratase ((3-elimination), cystathionine 3-synthase (metabolism of methionine), and cystathionine y-lyase (y-elimination). 

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... 

Step c of Eq. 24-34 may occur by ring opening to an enol phosphate which ketonizes to the observed product, but step e is a more complex multistep oxidative process.314a,b The last step is transamination to methionine with a glutamine-specific aminotransferase. Another enzyme from Klebsiella converts the same intermediate anion to methylthiopropionate, formate, and CO (Eq. 24-34, step/).315... 

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. 

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. 

All of the amino acids except lysine, threonine, proline, and hydroxyproline participate in transamination reactions. Transaminases exist for histidine, serine, phenylalanine, and methionine, but the major pathways of their metabolism do not involve transamination. Transamination of an amino group not at the a-position can also occur. Thus, transfer of 3-amino group of ornithine to a-ketoglutarate converts ornithine to glutamate-y-semialdehyde. 

Methionine can reversibly transaminate to form a primarily dead-end product. 

Aspartate is involved in the control point of pyrimidine biosynthesis (Reaction 1 below), in transamination reactions (Reaction 2 below), interconversions with asparagine (reactions 3 and 4), in the metabolic pathway leading to AMP (reaction 5 below), in the urea cycle (reactions 2 and 8 below), IMP de novo biosynthesis, and is a precursor to homoserine, threonine, isoleucine, and methionine (reaction 7 below). It is also involved in the malate aspartate shuttle. 

Some microorganisms in culture show methionine-dependent ethylene formation. In studies with Escherichia coli, 2-oxo-4-methylthiobutyrate (KMB) produced from methionine by transamination was suggested as the precursor of ethylene [19], and subsequently a cell-free system which produced ethylene from KMB in the presence of NAD(P)H, EDTA-Fe and oxygen was established [20]. An enzyme which catalysed a similar ethylene-forming activity was purified from Cryptococcus albidus [15]. The purified enzyme of molecular mass 62 kDa turned out to be NADH EDTA-Fe oxidoreductase. The proposed mechanism involves reduction of EDTA-Fe to EDTA-Fe by the enzyme, reduction of oxygen to superoxide by EDTA-Fe, of hydrogen peroxide to hydroxyl radical, and oxidation of KMB by hydroxyl radical to ethylene. However, an extensive physiological evaluation of this enzyme must be done before it can... 

Two of the enzymes involved in the methionine cycle, namely, MTA nucleosidase [46] and MTR kinase [47] were purified from plants and characterised. However, the plant enzyme catalysing the formation of KMB from MTR-P has not been characterised. In rat liver extracts, three enzymes are involved in the conversion [42]. The first enzyme isomerizes MTR-P to l-phospho-5-methylthioribulose (MTRu-P), the second enzyme produces two unidentified metabolites from MTRu-P, and the third enzyme catalyses the conversion of these two metabolites to KMB with the uptake of oxygen. Plants may produce KMB from MTR-P by similar enzymes. The last step of the methionine cycle that converts KMB to methionine is most likely a transamination, and this activity was also detected in avocado extracts in the presence of asparagine [45]. 

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.

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