Methionine synthesis and

A hypothesis has been proposed to explain all known causes of hyperho-mocysteinemia by a single, biochemical principle (Selhub and Miller 1992). The hypothesis emphasizes the existence of coordinate regulation by AdoMet of the partitioning of homocysteine between methionine synthesis and catabolism through cystathionine synthesis Elevated homocysteine levels in blood can be caused by a number of factors, including folate and B vitamin (B12, Bg) deficiency and pre-existing diseases such as atherosclerotic disease, diabetes and by various drugs. 

Sauer, H. and Wilmans, W. (1977) Cobalamin dependent methionine synthesis and methyl-folate-trap in human vitamin B 2 deficiency, B. J. Haematol., 36 189. 

Details of methionine synthesis and metabolism are discussed in conjunction with sulfur assimilation in the last article in this volume. As illustrated in Fig. 1, the synthesis of methionine constitutes a separate branch of the aspartate path-... 

The pathway of methionine synthesis and the properties of the enzymes involved were reviewed previously in this series by Giovanelli et al. (1980). The synthesis of methionine is summarized in Fig. 5. It shows that cysteine reacts with the C4 skeleton of phosphohomoserine to form cystathionine and that the original C3 skeleton of cysteine is then removed, thus effecting the transfer of the thiol group of cysteine to homoserine to form homocysteine. This route,... 

Other S/N ligands have been investigated in the enantioselective catalytic reduction of ketones with borane. Thus, Mehler and Martens have reported the synthesis of sulfur-containing ligands based on the L-methionine skeleton and their subsequent application as new chiral catalysts for the borane reduction of ketones." The in situ formed chiral oxazaborolidine catalyst has been used in the reduction of aryl ketones, providing the corresponding alcohols in nearly quantitative yields and high enantioselectivities of up to 99% ee, as shown in Scheme 10.60. 

In mammals and in the majority of bacteria, cobalamin regulates DNA synthesis indirectly through its effect on a step in folate metabolism, catalyzing the synthesis of methionine from homocysteine and 5-methyltetrahydrofolate via two methyl transfer reactions. This cytoplasmic reaction is catalyzed by methionine synthase (5-methyltetrahydrofolate-homocysteine methyl-transferase), which requires methyl cobalamin (MeCbl) (253), one of the two known coenzyme forms of the complex, as its cofactor. 5 -Deoxyadenosyl cobalamin (AdoCbl) (254), the other coenzyme form of cobalamin, occurs within mitochondria. This compound is a cofactor for the enzyme methylmalonyl-CoA mutase, which is responsible for the conversion of T-methylmalonyl CoA to succinyl CoA. This reaction is involved in the metabolism of odd chain fatty acids via propionic acid, as well as amino acids isoleucine, methionine, threonine, and valine. 

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. 

Dubnoff J, Borsook H (1948) Dimethylthetin and dimethyl-P-propiothetin in methionine synthesis. J Biol Chem 176 789-798... 

ACS activity may be reversibly regulated by various substances associated with the methionine-recycling pathway, SAM metabolism, and polyamine synthesis, and by natural and chemical analogues of SAM or inhibitors of PLP-dependent enzymes. 

Folic acid is a vitamin, as we developed in chapter 15. It is a complex molecule that serves as an essential precursor for coenzymes involved in the metabolism of one-carbon units. For example, folic acid-derived coenzymes are critically involved in the biosynthesis of thymidine for nucleic acid synthesis and methionine for protein biosynthesis. The synthesis of both demands donation of a methyl group and they come from folic acid-derived coenzymes. 

These three compounds exert many similar effects in nucleotide metabolism of chicks and rats [167]. They cause an increase of the liver RNA content and of the nucleotide content of the acid-soluble fraction in chicks [168], as well as an increase in rate of turnover of these polynucleotide structures [169,170]. Further experiments in chicks indicate that orotic acid, vitamin B12 and methionine exert a certain action on the activity of liver deoxyribonuclease, but have no effect on ribonuclease. Their effect is believed to be on the biosynthetic process rather than on catabolism [171]. Both orotic acid and vitamin Bu increase the levels of dihydrofolate reductase (EC 1.5.1.4), formyltetrahydrofolate synthetase and serine hydroxymethyl transferase in the chicken liver when added in diet. It is believed that orotic acid may act directly on the enzymes involved in the synthesis and interconversion of one-carbon folic acid derivatives [172]. The protein incorporation of serine, but not of leucine or methionine, is increased in the presence of either orotic acid or vitamin B12 [173]. In addition, these two compounds also exert a similar effect on the increased formate incorporation into the RNA of liver cell fractions in chicks [174—176]. It is therefore postulated that there may be a common role of orotic acid and vitamin Bj2 at the level of the transcription process in m-RNA biosynthesis [174—176]. 

Nitrous oxide, which is also called laughing gas, is a weak anesthetic. It is usually used together with hypnotics, analgesics, and muscle relaxants. It is sometimes called an ideal anesthetic because of the absence of any kind of suppressive influence on respiration. However, according to the latest information, use of nitrous oxide for more than 2 h is counterproductive since it causes a severe reduction of methionine synthesis, which in turn can cause a severe decrease in the level of vitamin Bj2 with all its subsequent consequences. 

Brossi, A. 1991. Mammalian alkaloids Conversion of tetrahydroisoquinoline-1-carboxylic acids derived from Dopamine. Planta Medica, 57 S93-S100 and, Xe, X. S., Tadic, D Brzostowska, M Brossi, A., Bell, M. and Creveling, C. 1991. Mammalian alkaloids - Synthesis and O-methylation of (S)-3 -hydroxycoclaurine and R-3 -hydroxycoclaurine and their N-methylated analogs with S-adenosyl-L-[methyl-C-14]methionine in presence of mammalian catechol O-methyltransferase. Helvetica Chimica Acta, 74 1399-1411. 

Danes, G., Kondrak, M., Banfalvi, Z. (2008). The effects of enhanced methionine synthesis on amino acid and anthocyanin content of potato tubers. BMC Plant Biol., 8, 65. 

Homocysteine (Hey) metabolism is closely linked to that of the essential amino acid methionine and thus plays a central role in several vital biological processes. Methionine itself is needed for protein synthesis and donates methyl groups for the synthesis of a broad range of vital methylated compounds. It is also a main source of sulphur and acts as the precursor for several other sulphur-containing amino acids such as cystathionine, cysteine and taurine. In addition, it donates the carbon skeleton for polyamine synthesis [1,2]. Hey is also important in the metabolism of folate and in the breakdown of choline. Hey levels are determined by its synthesis from methionine, which involves several enzymes, its remethylation to methionine and its breakdown by trans-sulphuration. 

Folic acid — Tetrahydro-folic acid Transfer one-carbon units 1 Synthesis of methionine, purines, and thymine 1... 

Most of the sulfur in plants occurs in proteins, especially in the amino acids cysteine and methionine. Other essential compounds that contain sulfur are coenzyme A, a compound essential for cellular respiration and for the synthesis and breakdown of fatty acids, and the vitamins thiamine and biotin. Sulfur can be absorbed by leaves as gaseous sulfur dioxide, S02, an environmental pollutant released from active volcanoes and from the burning of wood or fossil fuels. 

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