Big Chemical Encyclopedia

Chemical substances, components, reactions, process design ...

Articles Figures Tables About

Homocysteine from methionine

Synthesis of Sulfur Amino Acids. Of the many oxidation states of sulfur, only sulfite has been shown to be utilized by cell-free systems in the net synthesis of compounds with carbon-sulfur bonds, although mutant studies have indicated that more reduced forms can be incorporated. The formation of cysteinesulfinic acid from sulfite has been demonstrated in extracts of acetone-dried rabbit kidney it is possible that this reaction participates in the principal mechanism of sulfur incorporation. In many organisms that require preformed sulfur amino acids, cysteine may be formed from methionine. Only the sulfur of methionine is transferred to cysteine the carbon skeleton of cysteine is derived exclusively from serine. Transsulfuration appears to require the formation of homocysteine from methionine. Homocysteine and serine condense to form a thioether, cystathionine (V). Pyridoxal phosphate has been... [Pg.325]

The formation of homocysteine from methionine is thus an established fact. This homocysteine, in animals, and particularly in dogs, imder-goes a series of reactions, resulting in the oxidation of its sulfur and excretion of the latter in the form of sulfate or taurine (136). We are thus led to the study of the mechanisms of this oxidation. [Pg.378]

Figure 28-9. Conversion of homocysteine and serine to homoserine and cysteine. The sulfur of cysteine derives from methionine and the carbon skeleton from serine. Figure 28-9. Conversion of homocysteine and serine to homoserine and cysteine. The sulfur of cysteine derives from methionine and the carbon skeleton from serine.
Cobalamin-c disease remethylation of homocysteine to methionine also requires an activated form of vitamin B12. In the absence of normal B12 activation, homocystinuria results from a failure of normal vitamin B12 metabolism. Complementation analysis classifies defects in vitamin B12 metabolism into three groups cblC (most common), cblD and cblF. Most individuals become ill in the first few months or weeks of life with hypotonia, lethargy and growth failure. Optic atrophy and retinal changes can occur. Methylmalonate excretion is excessive, but less than in methylmalonyl-CoA mutase deficiency, and without ketoaciduria or metabolic acidosis. [Pg.677]

The question therefore arose about the fate of the methyl group from methionine. When minimal amounts of methionine were used to supplement the diet of rats given homocysteine as their main source of sulfur, the rats did not usually thrive, and at death had fatty accumulations in their livers. Best and his co-workers had earlier reported the efficacy of choline as a lipotropic agent, facilitating the mobilization of fat from the liver. Du Vigneaud therefore tried supplementing homcys-... [Pg.130]

Important pathways requiring SAM include synthesis of epinephrine and of the 7-methylgua-nine cap on eukaryotic mRNA, Synthesis of SAM from methionine is shown in Figure T17-3. After donating the methyl group, SAM is converted to homocysteine and remethylated in a reaction catalyzed by N-methyl THF-homocysteine methyltransferase requirii both vitamin Bj2 and N-meth d-THF. The methionine produced is once again used to make SAM. [Pg.249]

Figure 22.7 Homocysteine formation from methionine and formation of thiolactone from homocysteine. The homocysteine concentration depends upon a balance between the activities of homocysteine methyltransferase (methionine synthase) and cystathionine p-synthase. Both these enzymes require vitamin B12, so a deficiency can lead to an increase in the plasma level of homocysteine. (For details of these reactions, see Chapter 15.) Homocysteine oxidises spontaneously to form thiolactone, which can damage cell membrane. Figure 22.7 Homocysteine formation from methionine and formation of thiolactone from homocysteine. The homocysteine concentration depends upon a balance between the activities of homocysteine methyltransferase (methionine synthase) and cystathionine p-synthase. Both these enzymes require vitamin B12, so a deficiency can lead to an increase in the plasma level of homocysteine. (For details of these reactions, see Chapter 15.) Homocysteine oxidises spontaneously to form thiolactone, which can damage cell membrane.
Homocysteine. A sulfur-containing amino acid, a homologue of cysteine, produced by the demethylation of methionine, and an intermediate in the biosynthesis from methionine via cystathionine. [Pg.569]

Two essential enzymatic reactions in humans require vitamin B12 (Figure 33-2). In one, methylcobalamin serves as an intermediate in the transfer of a methyl group from /V5-methyltetrahydrofolate to homocysteine, forming methionine (Figure 33-2A Figure 33-3, section 1). Without vitamin B12, conversion of the major dietary and storage folate, N5-... [Pg.735]

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. [Pg.91]

The route from methionine to homocysteine is described in more detail in Figure 18-18 the conversion of homocysteine to a-ketobutyrate in Figure 22-14 the conversion of propionyl-CoA to succinyl-CoA in Figure 17-11. [Pg.682]

FIGURE 22-14 Biosynthesis of cysteine from homocysteine and serine in mammals. The homocysteine is formed from methionine, as described in the text. [Pg.845]

Cysteine is synthesized by two consecutive reactions in which homocysteine combines with serine, forming cystathionine, which, in turn, is hydrolyzed to a-ketobutyrate and cysteine (see Figure 20.8). Homocysteine is derived from methionine as described on p. 262. Because methionine is an essential amino acid, cysteine synthesis can be sustained only if the dietary intake of methionine is adequate. [Pg.266]

Cysteine is formed in plants and in bacteria from sulfide and serine after the latter has been acetylated by transfer of an acetyl group from acetyl-CoA (Fig. 24-25, step f). This standard PLP-dependent (3 replacement (Chapter 14) is catalyzed by cysteine synthase (O-acetylserine sulfhydrase).446 447 A similar enzyme is used by some cells to introduce sulfide ion directly into homocysteine, via either O-succinyl homoserine or O-acetyl homoserine (Fig. 24-13). In E. coli cysteine can be converted to methionine, as outlined in Eq. lb-22 and as indicated on the right side of Fig. 24-13 by the green arrows. In animals the converse process, the conversion of methionine to cysteine (gray arrows in Fig. 24-13, also Fig. 24-16), is important. Animals are unable to incorporate sulfide directly into cysteine, and this amino acid must be either provided in the diet or formed from dietary methionine. The latter process is limited, and cysteine is an essential dietary constituent for infants. The formation of cysteine from methionine occurs via the same transsulfuration pathway as in methionine synthesis in autotrophic organisms. However, the latter use cystathionine y-synthase and P-lyase while cysteine synthesis in animals uses cystathionine P-synthase and y-lyase. [Pg.1407]

There may be an added benefit for adults. N 5-methyltetrahydrofolate is required for the conversion of homocysteine to methionine (Figure 33-1 Figure 33-2, reaction 1). Impaired synthesis of N 5-methyltetrahydrofolate results in elevated serum concentrations of homocysteine. Data from several sources suggest a positive correlation between elevated serum homocysteine and occlusive vascular diseases such as ischemic heart disease and stroke. Clinical data suggest that the... [Pg.751]

During the remethylation of homocysteine to methionine, the methyl group from 5-MTHF is transferred to cobalamin, which serves as an... [Pg.228]

An alternative reaction for the remethylation of homocysteine to methionine can be accomplished by betaine homocysteine methyltrans-ferase, which uses betaine instead of 5-MTHF as the methyl donor. Unlike the MS reaction, which is believed to be ubiquitously present in all tissues, the betaine homocysteine methyl-transferase reaction occurs only in the liver and kidney. Betaine is not a required nutrient since the liver can synthesize betaine from choline. Betaine supplements, however, have been shown to lower plasma total homocysteine concentrations successfully in subjects with deficient homocysteine remethylation due to defects in MTHFR or MTRR and in those with deficient CBS activity. [Pg.229]

Figure 21-3. The methionine synthase reaction. Methionine synthase catalyzes the remethylation of homocysteine to methionine. In the first half reaction (1), a methyl group is transferred from 5-methyl tetrahydrofolate (5-MTHF) to the reduced form of cobalamin [Cob(I)], generating methyl-cobalamin [Methyl-Cob(III)] and tetrahydrofolate (THF). During the second half reaction (2), the methyl group is transferred from methylcobalamin to homocysteine, generating methionine. During the catalytic reaction, Cob(I) occasionally becomes oxidized, producing an inactive form of cobalamin, cob(II)alamin [Cob(II)]. The enzyme methionine synthase reductase (MTRR) then reactivates Cob(II) through reductive methylation, producing methyl-Cob(III). SAM, 5-adenosylmethionine SAH, 5-adeno-sylhomocysteine. Figure 21-3. The methionine synthase reaction. Methionine synthase catalyzes the remethylation of homocysteine to methionine. In the first half reaction (1), a methyl group is transferred from 5-methyl tetrahydrofolate (5-MTHF) to the reduced form of cobalamin [Cob(I)], generating methyl-cobalamin [Methyl-Cob(III)] and tetrahydrofolate (THF). During the second half reaction (2), the methyl group is transferred from methylcobalamin to homocysteine, generating methionine. During the catalytic reaction, Cob(I) occasionally becomes oxidized, producing an inactive form of cobalamin, cob(II)alamin [Cob(II)]. The enzyme methionine synthase reductase (MTRR) then reactivates Cob(II) through reductive methylation, producing methyl-Cob(III). SAM, 5-adenosylmethionine SAH, 5-adeno-sylhomocysteine.
Vitamin B12 is required by only two enzymes in human metabolism methionine synthetase and L-methylmalonyl-CoA mutase. Methionine synthetase has an absolute requirement for methylcobalamin and catalyzes the conversion of homocysteine to methionine (Fig. 28-5). 5-Methyltetrahydrofolate is converted to tetrahydrofolate (THF) in this reaction. This vitamin B12-catalyzed reaction is the only means by which THF can be regenerated from 5-methyltetrahydrofolate in humans. Therefore, in vitamin B12 deficiency, folic acid can become trapped in the 5-methyltetrahydrofolate form, and THF is then unavailable for conversion to other coenzyme forms required for purine, pyrimidine, and amino acid synthesis (Fig. 28-6). All folate-dependent reactions are impaired in vitamin B12 deficiency, resulting in indistinguishable hematological abnormalities in both folate and vitamin B12 deficiencies. [Pg.308]

The importance of the cycle depicted in Fig. 15-20 is that it conserves homocysteine. Methionine and cysteine that are used for protein synthesis will deplete homocysteine from the cycle so at least methionine must be replaced in the diet. [Pg.450]

As discussed in Section 10.3.4.2, the metabolic fate of homocysteine arising from methionine is determined not only by the activity of cystathionine synthetase and cystathionase, hut also the rate at which it is remethylated to methionine (which is dependent on vitamin B12 and folate status) and the requirement for cysteine. [Pg.256]

The catalysis of the transfer of a methyl group is an important role of enzyme-bound vitamin B12 derivatives in human, animal, and bacterial metabolism. The known enzyme-controlled methyl group-transfer reactions are key steps in the cobamide-dependent methylations of homocysteine to methionine, in the metabolic formation of methane from other Ci-compounds in methanogenic bacteria, and in the fixation of carbon dioxide via the acetyl coenzyme A pathway of some bacterial autotrophs (Figure 10). ... [Pg.807]

The coenzyme that mediates this transfer of a methyl group is methylcobalamin, derived from vitamin Bj2- In fact, this reaction and the rearrangement of 1-methylmalonyl CoA to succinyl CoA (Section 23.5.4), catalyzed by a homologous enzyme, are the only two Bj2-dependent reactions known to take place in mammals. Another enzyme that converts homocysteine into methionine without vitamin Bj2 also is present in many organisms. [Pg.999]

The second reaction requiring vitamin B12 catalyzes the conversion of homocysteine to methionine and is catalyzed by methionine synthase. This reaction results in the transfer of the methyl group from N -methyltetrahydrofolate to hydroxycobalamin generating tetrahydrofolate and methylcobalamin during the process of the conversion. [Pg.249]

Melhyl-HLjfolate is a cofactor of methiojiinc synthase. Methionine synthase cata-lyzes the transfer of the 1-carbon unit from methyl-H folate to homocysteine, generating methionine. Methionine synthase also uses vitamin 5 2 as a cofactor. [Pg.497]

A. Pernicious anemia occurs when the stomach does not produce adequate intrinsic factor for absorption of vitamin B12, which is required for the conversion of methylmalonyl CoA to succinyl CoA and homocysteine to methionine. A vitamin B12 deficiency results in the excretion of methylmalonic acid and an increased dietary requirement for methionine. The methyl group transferred from vitamin B12 to homocysteine to form methionine comes from 5 -methyl tetrahydrofolate, which accumulates in a vitamin B12 deficiency, causing a decrease in folate levels and symptoms of folate deficiency, including increased levels of FIGLU and decreased purine biosynthesis. [Pg.271]

The most reduced coenzyme is 5-methyl tetrahydrofolate poly glutamate. It is the source of the methyl group added to homocysteine regenerating methionine and tetrahydrofolate ready to accept a one-carbon unit from formate or serine. This last reaction is where folic acid and vitamin come together (Figs. 8.49, 8.52, and 8.53). The implications of this reaction and how folic acid can mask pernicious anemia are discussed in the seetion on vitamin Big (cyanocobalamin). Note that the formation of 5-methyl-THF nor-mdly is not reversible. Tetrahydrofolate can be regenerated only if there is adequate methyl cobalamin coenzyme. [Pg.407]

Cobalmin Deficiency. Pernicious anemia is the disease associated with vitamin Bi2 deficiency. It is usually caused by the inability to produce intrinsic factor. Indeed, many times the vitamin must be administered by injection. The blood picture, a megaloblastic anemia, is indistinguishable from that caused by folic acid deficiency. Indeed folic acid supplements can mask the blood picture. This is illustrated in Fig. 8.53. Removal of ad-enosyl cobalamin eliminates the regeneration of tetrahydrofolate during the methylation of homocysteine to methionine. Folic acid supplements provide a fresh source of tetrahydrofolate coenzymes. DNA synthesis can continue and new erythrocytes form. Excess folic acid also may compete for the available vitamin, further exacerbating vitamin deficiency. [Pg.415]

Methionine and cysteine are the principal sources of organic sulfur in humans. Methionine is essential (unless adequate homocysteine and a source of methyl groups are available), but cysteine is not, since it can be synthesized from methionine. [Pg.353]


See other pages where Homocysteine from methionine is mentioned: [Pg.202]    [Pg.331]    [Pg.202]    [Pg.331]    [Pg.298]    [Pg.16]    [Pg.130]    [Pg.131]    [Pg.739]    [Pg.1702]    [Pg.67]    [Pg.206]    [Pg.84]    [Pg.287]    [Pg.93]    [Pg.287]    [Pg.287]    [Pg.308]    [Pg.1102]    [Pg.13]   
See also in sourсe #XX -- [ Pg.559 ]




SEARCH



Homocysteine

© 2024 chempedia.info