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Methylmalonyl

Fatty acids derived from animal and vegetable sources generally contain an even number of carbon atoms siace they are biochemically derived by condensation of two carbon units through acetyl or malonyl coenzyme A. However, odd-numbered and branched fatty acid chains are observed ia small concentrations ia natural triglycerides, particularly mminant animal fats through propionyl and methylmalonyl coenzyme respectively. The glycerol backbone is derived by biospeciftc reduction of dihydroxyacetone. [Pg.122]

Adenosylcobalamin (coenzyme B 2) is required in a number of rearrangement reactions that occurring in humans is the methylmalonyl-Co A mutase-mediated conversion of (R)-methylmalonyl-Co A (6) to succinjl-CoA (7) (eq. 1). The mechanism of this reaction is poorly understood, although probably free radical in nature (29). The reaction is involved in the cataboHsm of valine and isoleucine. In bacterial systems, adenosylcobalamin drives many 1,2-migrations of the type exemplified by equation 1 (30). [Pg.112]

There is one exception to the rule that requires bulky hydrophobic residues to fill the interior of eight-stranded a/p barrels in order to form a tightly packed hydrophobic core. The coenzyme Biz-dependent enzyme methylmalonyl-coenzyme A mutase, the x-ray structure of which was determined by Phil Evans and colleagues at the MRC Laboratory of Molecular... [Pg.50]

Figure 4.4 Schematic diagram of the structure of the a/p-barrel domain of the enzyme methylmalonyl-coenzyme A mutase. Alpha helices are red, and p strands are blue. The inside of the barrel is lined by small hydrophilic side chains (serine and threonine) from the p strands, which creates a hole in the middle where one of the substrate molecules, coenzyme A (green), binds along the axis of the barrel from one end to the other. (Adapted from a computer-generated diagram provided by P. Evans.)... Figure 4.4 Schematic diagram of the structure of the a/p-barrel domain of the enzyme methylmalonyl-coenzyme A mutase. Alpha helices are red, and p strands are blue. The inside of the barrel is lined by small hydrophilic side chains (serine and threonine) from the p strands, which creates a hole in the middle where one of the substrate molecules, coenzyme A (green), binds along the axis of the barrel from one end to the other. (Adapted from a computer-generated diagram provided by P. Evans.)...
Mancia, E., et al. How coenzyme Biz radicals are generated the crystal structure of methylmalonyl-coen-zyme A mutase at 2 A resolution. Strueture 4 339-350, 1996. [Pg.65]

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. [Pg.791]

D-Methylmalonyl-CoA, the product of this reaction, is converted to the L-isomer by methylmalonyl-CoA epunerase (Figure 24.19). (This enzyme has often and incorrectly been called methylmalonyl-CoA racemase. It is not a racemase because the CoA moiety contains five other asymmetric centers.) The epimerase reaction also appears to involve a carbanion at the a-position (Figure 24.20). The reaction is readily reversible and involves a reversible dissociation of the acidic a-proton. The L-isomer is the substrate for methylmalonyl-CoA mutase. Methylmalonyl-CoA epimerase is an impressive catalyst. The for the proton that must dissociate to initiate this reaction is approximately 21 If binding of a proton to the a-anion is diffusion-limited, with = 10 M sec then the initial proton dissociation must be rate-limiting, and the rate constant must be... [Pg.791]

The turnover number of methylmalonyl-CoA epimerase is 100 sec and thus the enzyme enhances the reaction rate by a factor of 10. ... [Pg.791]

FIGURE 24.20 The methylmalonyl-CoA epimerase mechanism involves a resonance-stabilized carbanion at the oj-position. [Pg.791]

A Bi9-Catalyzed Rearrangement Yields Succinyl-CoA from L-Methylmalonyl-CoA... [Pg.792]

FIGURE 24.21 A mechanism for the methylmalonyl-CoA mntase reaction. In the first step, Co is rednced to Co dne to homolytic cleavage of the Co —C bond in cobalamin. Hydrogen atom transfer from methylmalonyl-CoA yields a methylmalonyl-CoA radical that can undergo rearrangement to form a snccinyl-CoA radical. Transfer of an H atom regenerates the coenzyme and yields snccinyl-CoA. [Pg.792]

Based on the mechanism for the methylmalonyl-CoA mutase (Eigure 24.21), write reasonable mechanisms for the reactions shown below. [Pg.800]

Biotin is involved in carboxylation and decarboxylation reactions. It is covalently bound to its enzyme. In the carboxylase reaction, C02 is first attached to biotin at the ureido nitrogen, opposite the side chain in an ATP-dependent reaction. The activated C02 is then transferred from carboxybiotin to the substrate. The four enzymes of the intermediary metabolism requiring biotin as a prosthetic group are pyruvate carboxylase (pyruvate oxaloacetate), propionyl-CoA-carboxylase (propionyl-CoA methylmalonyl-CoA), 3-methylcroto-nyl-CoA-carboxylase (metabolism of leucine), and actyl-CoA-carboxylase (acetyl-CoA malonyl-CoA) [1]. [Pg.270]

Methylmalonyl-CoA mutase 5 -deoxyadenosylco-balamin is part of dimethylbenzimidazolecobamide coenzyme, a constituent of methylmalonyl-CoA mutase. This mutase catalyses the isomerization of methylmalonyl-CoA to succinyl-CoA (anaplerotic reaction of the citric acid cycle). [Pg.1291]

Succinyl-coenzyme A H -COSR COOH L-Methylmalonyl coenzyme ... [Pg.440]

Methylmalonyl CoA mutase, leucine aminomutase, and methionine synthase (Figure 45-14) are vitamin Bj2-dependent enzymes. Methylmalonyl CoA is formed as an intermediate in the catabolism of valine and by the carboxylation of propionyl CoA arising in the catabolism of isoleucine, cholesterol, and, rarely, fatty acids with an odd number of carbon atoms—or directly from propionate, a major product of microbial fer-... [Pg.492]

Thus, AMDase requires no cofactors and this fact is entirely different from those of known analogous enzymes, such as acyl-CoA carboxylases, methylmalonyl-CoA decarboxylases " and transcarboxylases. [Pg.312]

Monooxygenase, Isopenicillin N synthase, Glutathione peroxidase, Methylmalonyl-CoA mutase, PLP-dependent b-lyase... [Pg.21]

The present chapter reviews applications in biocatalysis of the ONIOM method. The focus is on studies performed in our research group, in most cases using the two-layer ONIOM(QM MM) approach as implemented in Gaussian [23], The studied systems include methane monooxygenase (MMO), ribonucleotide reductase (RNR) [24, 25], isopenicillin N synthase (IPNS) [26], mammalian Glutathione peroxidase (GPx) [27,28], Bi2-dependent methylmalonyl-CoA mutase [29] and PLP-dependent P-lyase [30], These systems will be described in more detail in the following sections. ONIOM applications to enzymatic systems performed by other research groups will be only briefly described. [Pg.31]

However, in some cases the reaction coordinate actually extends from the initial active-site selection into the protein, and the same-configuration solution is not adequate. One example appears in the study of Methylmalonyl-CoA mutase described below. Another drawback of a static optimization scheme is that it... [Pg.31]

Methylmalonyl-CoA mutase (MCM) catalyzes a radical-based transformation of methylmalonyl-CoA (MCA) to succinyl-CoA. The cofactor adenosylcobalamin (AdoCbl) serves as a radical reservoir that generates the S -deoxyadenosine radical (dAdo ) via homolysis of the Co—C5 bond [67], The mechanisms by which the enzyme stabilizes the homolysis products and achieve an observed 1012-fold rate acceleration are yet not fully understood. Co—C bond homolysis is directly kineti-cally coupled to the proceeding hydrogen atom transfer step and the products of the bond homolysis step have therefore not been experimentally characterized. [Pg.43]

The ONIOM protein system contains the substrate, methylmalonyl-CoA, bound to the active site, the cofactor (AdoCbl) and all amino acids within a 15-A radius from the cobalt atom. The active-site selection contains a truncated AdoCbl and the imidazole ring of its lower ligand. The QM part was calculated using the BP86 functional [31, 72] because it gives better agreement with experimental Co—C bond energies [73, 74], This a different choice of functional compared to the other studies in the present review. [Pg.44]

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. [Pg.100]


See other pages where Methylmalonyl is mentioned: [Pg.625]    [Pg.387]    [Pg.51]    [Pg.791]    [Pg.791]    [Pg.791]    [Pg.791]    [Pg.791]    [Pg.792]    [Pg.155]    [Pg.155]    [Pg.155]    [Pg.262]    [Pg.83]    [Pg.309]    [Pg.21]    [Pg.43]    [Pg.51]   
See also in sourсe #XX -- [ Pg.295 , Pg.296 , Pg.298 ]




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5- Methylmalonyl-CoA equilibrium constant

5- Methylmalonyl-CoA in branched chain formation

Biotin Methylmalonyl

Enzyme methylmalonyl-CoA mutase

Ethyl methylmalonyl chloride

Methylmalonyl CoA carboxylase mutase

Methylmalonyl coenzyme

Methylmalonyl coenzyme A epimerase

Methylmalonyl coenzyme A isomerase

Methylmalonyl isomerase

Methylmalonyl pathway

Methylmalonyl-/succinyl

Methylmalonyl-CoA

Methylmalonyl-CoA decarboxylase

Methylmalonyl-CoA epimerase

Methylmalonyl-CoA isomerase

Methylmalonyl-CoA mutase

Methylmalonyl-CoA mutase activity

Methylmalonyl-CoA mutase mechanism

Methylmalonyl-CoA mutase stereochemistry

Methylmalonyl-CoA mutase three-dimensional structure

Methylmalonyl-CoA racemase

Methylmalonyl-coenzyme A mutase

Rearrangement methylmalonyl—succinyl

Vitamin methylmalonyl CoA mutase

Vitamin methylmalonyl-succinyl

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