Homocysteine structure

Three-dimensional X-ray crystal structures of the SET domains of >10 PMTs and the catalytic domain of DOT1L have been reported to date [25-27]. These structures, either in the apo-state or when bound to the cofactor product S-adenosyl-L-homocysteine (SAH), a histone peptide, or an inhibitor, yield key structural insights into enzyme/substrate/cofactor/inhibitor interactions and inform approaches to further inhibitor design. 

Figure 15.12 The modular structure of methionine synthase. The four domains are connected by flexible hinges, which allow the CH3tetrahydrofolate-, AdoMet- or homocystein-binding domains to alternatively access the B12-binding domain. (From Bannerjee and Ragsdale, 2003. Reprinted with permission from Annual Reviews.)...

Figure 22.6 How various factors increase the risk of atherosclerosis, thrombosis and myocardial infarction. The diagram provides suggestions as to how various factors increase the risk of development of the trio of cardiovascular problems. The factors include an excessive intake of total fat, which increases activity of clotting factors, especially factor VIII an excessive intake of saturated or trans fatty acids that change the structure of the plasma membrane of cells, such as endothelial cells, which increases the risk of platelet aggregation or susceptibility of the membrane to injury excessive intake of salt - which increases blood pressure, as does smoking and low physical activity a high intake of fat or cholesterol or a low intake of antioxidants, vitamin 6 2 and folic acid, which can lead either to direct chemical damage (e.g. oxidation) to the structure of LDL or an increase in the serum level of LDL, which also increases the risk of chemical damage to LDL. A low intake of folate and vitamin B12 also decreases metabolism of homocysteine, so that the plasma concentration increases, which can damage the endothelial membrane due to formation of thiolactone.

Accumulation of homocysteine and reduced transsulfation of various compounds leads to abnormalities in connective tissue structures that cause altered blood vessel wall structure, loss of skeletal bone density (osteoporosis), dislocated optic lens (ectopia lentis), and increased risk of blood clots. 

Zhang et al. [197] have studied adsorption of DL-homocysteine and L-homo-cysteine thiolactone on Au(lll) electrode in 0.1 M HCIO4 using CV and STM. Both compounds formed highly ordered adlayer on Au(lll). For both adlayers, structural models have been proposed. 

Vitamin B12 consists of a porphyrin-like ring structure, with an atom of Co chelated at its centre, linked to a nucleotide base, ribose and phosphoric acid (6.34). A number of different groups can be attached to the free ligand site on the cobalt. Cyanocobalamin has -CN at this position and is the commercial and therapeutic form of the vitamin, although the principal dietary forms of B12 are 5 -deoxyadenosylcobalamin (with 5 -deoxyadeno-sine at the R position), methylcobalamin (-CH3) and hydroxocobalamin (-OH). Vitamin B12 acts as a co-factor for methionine synthetase and methylmalonyl CoA mutase. The former enzyme catalyses the transfer of the methyl group of 5-methyl-H4 folate to cobalamin and thence to homocysteine, forming methionine. Methylmalonyl CoA mutase catalyses the conversion of methylmalonyl CoA to succinyl CoA in the mitochondrion. 

Sauls DL, Wolberg AS, Hoffman M. Elevated plasma homocysteine leads to alterations in fibrin clot structure and stability implications for the mechanism of thrombosis in hyperhomocysteinemia. J Thromb Haemost 2003 l(2) 300-306. 

The structure of omapatrilat contains an l-homocysteine residue, which is highlighted in the formula shown below. In a published synthesis of this compound, the first step is the separation of enantiomers of a homocysteine derivative [4]. 

In Figure 1 the equilibrium spatial structures of adsorption complexes of sulfur-containing amino acids cysteine, methionine, homocysteine and cystine on a silica surface obtained from gas phase are shown. 

Equilibrium structures of complexes silica with sulfur-containing aminoacids in gas cysteine-silica b - homocysteine-silica c - methionine-silica d - cystine-silica. 

Homocysteine, first described by Butz and Vincent duVigneaud in 1932, is a sulfur-containing amino acid that is structurally and metabolically linked to the dietary amino acids methionine and cysteine (Fig. 21-1). Homocysteine is found in both prokaryotic and eukaryotic organisms and is a sensitive marker of vitamin deficiency and kidney function. 

Figure 21-1. Structural and metabolic relationships between methionine, homocysteine, and cysteine. CBS, cystathionine b-synthase CTH, cystathionine y-lyase MAT, methionine adenosyltransferase MS, methionine synthase 5-MTHF, 5-methyltetrahydrofoIate MTs, methyl transferases PLR pyridoxal phosphate SAH, S-adenosylhomocysteine SAHH, SAH hydrolase THF, tetrahydrofolate.

Many different applications for gold cysteine nanoclusters have been proposed. One application is the use of citrate capped nanoparticles as sensors for the detection of thiol containing stractures. This application rehes on the fact that thiols can easily displace oxygen coordinated moieties. Zhong et al. have studied this process between cysteine and homocysteine to develop an assay for the homocysteine biomarker, a correlate to cardiovascular disease. When citrate stabilized particles of 13 run were incubated with either thiolate structure, the solution color changed from a dark red to a deep blue. The displacement of citrate by these moieties resulted... 

Freer, S. T. and Kraut, J. (1965). Crystal structures of D,L-homocysteine thiolac-tone hydrochloride two polymorphic forms and a hybrid. Acta Crystallgr, 19, 992-1002. [30, 79]... 

FIGURE 6.2 Phosphatidylcholine (PC) synthesis by the CDP-ethanolamine pathway. Structures of ethanolamine and choline. The nucleotide moiety S-adenosyl methionine (SAM) is requiivct to transfer the methyl group of methionine to phosphatidylethanolamine (J E) to form PC. In the process, SAM is converted to S-adenosyl homocysteine (SAH). The nitrogen atom of PC has four covalent bonds and is called a quaternary amine. It bears a positive charge that is not influenced by changes in the pH of the suitoimding fluids. The PE methyltran.sferase pathway of I C synthesis occurs only in the liver. 

Vtamin A supplementation, 564-565 Vitamin B(, 493, 541-542 aminotranK/ei ase, 209 assessmenl of status, 546-550 biochcinistry, 542-545 cardiovascular disease and, 553 homocysteine and, 550-554 homocysbnuria, 550,554 toxidty, 550 water solubility, 27 Vitamin Bs deficiency, 545-546 Vitamin supplements, 551 Vitamin Bu, 493,507, 516 absorption, 81-82 assessment of status, 522-524 biocbemistry, 516-517 chemical structure, 517 Cobalt and, 4t homocystBine and, 553 Vitamin Bij dehdency, 517-524 causes of, 518-522 elderly population, 521,553 folate deficiency and, 507, 511-312, 518 hematologic signs, 513... 

The derivatives of methionine formed by haloketones are not stable to the usual conditions of acid hydrolysis. These sulfonium salts are degraded in three different ways. Some methionine is regenerated, some homoserine and homoserine lactone is formed and possibly the homocysteine derivative of the general structure indicated below is produced where X represents the rest of the affinity label. 

The crystal structure of 5-8-azaadenosyl-L-homocysteine has been examined because this substance inhibits a methyltransferase that depends on S -adenosyl-L-methionine as a cofactor. ... 

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