Methionine pathway

Choline occupies a key position between energy and protein metabolism. Two types of choline functions are known as choline per se, for which the choline moiety is required, and in the function of a methyl donor. Choline per se plays a major role in lipid metabolism, particularly in lipid transport, as lipotropic agent, but it is also an important source of labile methyl groups for the biosynthesis of other methylated compounds. Based on this second function, choline and methionine pathways partially overlap in providing methyl groups in a variety of reactions. Based on these assumptions we investigated the effects of rumen protected choline administration on milk production in dairy cows. To achieve this pourpose a meta-analysis was carried out to summarize available scientific evidence for the effect of oral rumen protected choline (RPC) supplementation in dairy cows. 

Kromer, J.O., M. Fritz, E. Heinzle and C. Wittmann, 2005. In vivo quantification of intracellular amino acids and intermediates of the methionine pathway in Corynebacterium glutamicum. Anal Biochem 340, 171-173. 

Modulation of second-messenger pathways is also an attractive target upon which to base novel antidepressants. Rolipram [61413-54-5] an antidepressant in the preregistration phase, enhances the effects of noradrenaline though selective inhibition of central phosphodiesterase, an enzyme which degrades cycHc adenosiae monophosphate (cAMP). Modulation of the phosphatidyl iaositol second-messenger system coupled to, for example, 5-HT,, 5-HT,3, or 5-HT2( receptors might also lead to novel antidepressants, as well as to alternatives to lithium for treatment of mania. Novel compounds such as inhibitors of A-adenosyl-methionine or central catechol-0-methyltransferase also warrant attention. 

Fohc acid is a precursor of several important enzyme cofactors required for the synthesis of nucleic acids (qv) and the metaboHsm of certain amino acids. Fohc acid deficiency results in an inabiUty to produce deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and certain proteins (qv). Megaloblastic anemia is a common symptom of folate deficiency owing to rapid red blood cell turnover and the high metaboHc requirement of hematopoietic tissue. One of the clinical signs of acute folate deficiency includes a red and painhil tongue. Vitamin B 2 folate share a common metaboHc pathway, the methionine synthase reaction. Therefore a differential diagnosis is required to measure foHc acid deficiency because both foHc acid and vitamin B 2 deficiency cause... 

Fatty acids with odd numbers of carbon atoms are rare in mammals, but fairly common in plants and marine organisms. Humans and animals whose diets include these food sources metabolize odd-carbon fatty acids via the /3-oxida-tion pathway. The final product of /3-oxidation in this case is the 3-carbon pro-pionyl-CoA instead of acetyl-CoA. Three specialized enzymes then carry out the reactions that convert propionyl-CoA to succinyl-CoA, a TCA cycle intermediate. (Because propionyl-CoA is a degradation product of methionine, valine, and isoleucine, this sequence of reactions is also important in amino acid catabolism, as we shall see in Chapter 26.) The pathway involves an initial carboxylation at the a-carbon of propionyl-CoA to produce D-methylmalonyl-CoA (Figure 24.19). The reaction is catalyzed by a biotin-dependent enzyme, propionyl-CoA carboxylase. The mechanism involves ATP-driven carboxylation of biotin at Nj, followed by nucleophilic attack by the a-carbanion of propi-onyl-CoA in a stereo-specific manner. 

Divalent sulfur compounds are achiral, but trivalent sulfur compounds called sulfonium stilts (R3S+) can be chiral. Like phosphines, sulfonium salts undergo relatively slow inversion, so chiral sulfonium salts are configurationally stable and can be isolated. The best known example is the coenzyme 5-adenosylmethionine, the so-called biological methyl donor, which is involved in many metabolic pathways as a source of CH3 groups. (The S" in the name S-adenosylmethionine stands for sulfur and means that the adeno-syl group is attached to the sulfur atom of methionine.) The molecule has S stereochemistry at sulfur ana is configurationally stable for several days at room temperature. Jts R enantiomer is also known but has no biological activity. 

The result is not totally surprising, because hydride ion shifts are known in many methylations. Thus, it was proposed that the methyl carbinol is formed by the sequence methylation of a double bond - hydride shift - formation of terminal methylene - epoxidation - opening of the epoxide to aldehyde - reduction to carbinol (Scheme 6). The pathway can explain well the loss of two original hydrogens in methionine methyl group. 

FIGURE 3.27 Dioxygenation of enediol to formate + CO in the methionine salvage pathway. 

Wray JW, RH Abeles (1995) The methionine salvage pathway in Klebsiella pneumoniae and rat liver. J Biol Chem 270 3147-3153. 

Although the pathway has not been established, relatively high yields of trimethyltin from inorganic tin have been observed in yeast concomitant with the degradation of butyltin compounds (Errecalde et al. 1995). Exceptionally, methionine transferase may carry out the methylation of Hg in Neurospora crassa (Landner 1971) and thiopurine methyltransferase the methylation of inorganic Se in Escherichia coli (Ranjard et al. 2003). 

Figure 3. Reaction Mechanism for N-Glucuronyloxy Arylamides (III) and Arylamines (IV). Ac acetyl RSCH3, methionine RCH, C8-guanine-nucleosides, -nucleotides, or -nucleic acids. Pathways a, b, and c are discussed in the text.

RSCH3, methionine RNH2> N -guanine- and N -adenine-nucleosides or -nucleic acids RCH, C8-guanine-nucleosides or -nucleic acids. The dashed arrow indicates a proposed pathway. 

These reactions to 4-methylthiobutyl glucosinolate, the precursor for sulforaphane formation, have been extensively studied in Eruca sativa (arugula, rocket).64 A gene controlling variation in the glucosinolates of Arabidopsis is part of the methionine elongation pathway just described.65... 

DMSP is formed from L-methionine required processes, not necessarily in this order, are methylation, deamination, and decarboxylation. Several available pathways have been comprehensively reviewed.35... 

The amino acid L-tryptophan is the precursor for the synthesis of 5-HT. The synthesis and primary metabolic pathways of 5-HT are shown in Figure 13-5. The initial step in the synthesis of serotonin is the facilitated transport of the amino acid L-tryptophan from blood into brain. The primary source of tryptophan is dietary protein. Other neutral amino acids, such as phenylalanine, leucine and methionine, are transported by the same carrier into the brain. Therefore, the entry of tryptophan into brain is not only related to its concentration in blood but is also a function of its concentration in relation to the concentrations of other neutral amino acids. Consequently, lowering the dietary intake of tryptophan while raising the intake of the amino acids with which it competes for transport into brain lowers the content of 5-HT in brain and changes certain behaviors associated with 5-HT function. This strategy for lowering the brain content of 5-HT has been used clinically to evaluate the importance of brain 5-HT in the mechanism of action of psychotherapeutic drugs. 

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