Methionine compounds

Sulfur. Sulfur is present in every cell in the body, primarily in proteins containing the amino acids methionine, cystine, and cysteine. Inorganic sulfates and sulfides occur in small amounts relative to total body sulfur, but the compounds that contain them are important to metaboHsm (45,46). Sulfur intake is thought to be adequate if protein intake is adequate and sulfur deficiency has not been reported. Common food sources rich in sulfur are Hsted in Table 6. 

Detoxifica.tlon. Detoxification systems in the human body often involve reactions that utilize sulfur-containing compounds. For example, reactions in which sulfate esters of potentially toxic compounds are formed, rendering these less toxic or nontoxic, are common as are acetylation reactions involving acetyl—SCoA (45). Another important compound is. Vadenosylmethionine [29908-03-0] (SAM), the active form of methionine. SAM acts as a methylating agent, eg, in detoxification reactions such as the methylation of pyridine derivatives, and in the formation of choline (qv), creatine [60-27-5] carnitine [461-06-3] and epinephrine [329-65-7] (50). 

Although molybdenum is an essential element, excess levels can have deleterious effects. The LD q and TLV values of the most common Mo compounds are Hsted in Table 3 (63,64). In general the toxicity of Mo compounds is considered to be low. For example, M0S2 has been found to be virtually nontoxic even at high levels. Certain Mo compounds such as MoCl and Mo(CO), have higher toxicity because of the chemical nature and reactivity of these compounds rather than the Mo content. Supplementary dietary Cu ", thiosulfate, methionine, and cysteine have been shown to be effective in alleviating Mo toxicity in animals. 

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. 

Folate antagonists (eg, methotrexate and certain antiepileptics) are used ia treatment for various diseases, but their adininistration can lead to a functional folate deficiency. Folate utilization can be impaired by a depletion of ziac (see Zinc compounds). In humans, the intestinal bmsh border folate conjugase is a ziac metaHoenzyme (72). One study iadicates that the substantial consumption of alcohol, when combiaed with an iaadequate iatake of folate and methionine, may iacrease the risk of colon cancer (73). Based on this study, it is recommended to avoid excess alcohol consumption and iacrease folate iatake to lower the risk of colon cancer. 

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. 

Systematic screening experiments have identified more than 100 synthetic compounds with potent antiangiogenic activity. The mode of action for most of these molecules is not well understood, but some of the 40 compounds are well advanced in clinical trials (Table 3). The first substance to have entered clinical trials was the Fumagillin-derivative AGM 1470. Fumagillin is an antibiotic which inhibits bFGF- and PDGF-induced endothelial cell proliferation. The mechanism of action of AGM 1470 is poorly understood, but it was shown that it binds and inhibits the metalloprotease methionine aminopeptidase (MetAp-2). 

S-adenosyl-L-methionine (AdoMet, SAM) is a cofactor and the most important donor of the methyl (CH3-) group for methyltransferases, including COMT. When the methyl-group has been transferred, the remaining demethylated compound is called S-adenosyl-L-homo-cysteine. 

Biocatalytic access to both antipodal sulfoxides was exploited in total syntheses of bioactive compounds, which is outlined in some representative examples. Biooxidation of functionalized dialkyl sulfides was utilized in the direct synthesis of both enantiomers of sulforaphane and some analogs in low to good yields and stereoselectivities (Scheme 9.27) [206]. This natural product originates from broccoli and represents a potent inducer of detoxification enzymes in mammalian metabolism it might be related to anticarcinogenic properties of plants from the cruciform family. All four possible stereoisomers of methionine (R = Me) and ethionine sulfoxides... 

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 11.9 Elimination reactions during metabolism of aliphatic sulfur compounds (a) cysteine, (b) methionine, and (c) 2-dimethylsulfoniopropionate. 

Primary and secondary products, and end-products of lipid peroxidation have all been shown to accumulate in senile cataracts (Babizhayev, 1989b Simonelli et al., 1989). Accumulation of these compounds in the lenticular epithelial membranes is a possible cause of damage preceding cataract formation. In senile cataracts there is also extensive oxidation of protein methionine and cysteine in both the membrane and cytosol components (Garner and Spector, 1980), while in aged normal lenses a lesser extent of oxidation was confined to the membrane. The authors therefore suggested that oxidation of membrane components was a precataract state. 

Tonzetich J, Carpenter PAW. 1971. Production of volatile sulphur compounds from cysteine, cystine and methionine by human dental plaque. Arch Oral Biol 16 599-607. 

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. 

Selectivity studies with DTU indicated marked discrimination in the clathrate formation 23,45). As in other types of clathrates, the steric factor is important in differentiation between compounds of similar functionality but different shape. For example, DTU forms crystalline complexes with some alcohols (methanol, ethanol, propanol, 1-butanol) but not with others (2-butanol). It complexes the ethyl esters of N-acetyl derivatives of glycine, alanine, methionine and aspartic acid, but not of proline, serine, phenylalanine and glutamic acid. 

Some hair-coloring products contain the water-soluble compound lead (II) acetate, Pb(CH3COO)2. When the coloring product is applied to the hair, a chemical reaction occurs between the Pb2+ ion and the sulfur atoms in cysteine and methionine incorporated in amino acids in hair proteins. The insoluble black product lead(II) sulfide forms. 

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