Methylmalonyl-CoA mutase

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methylmalonyl Coenzyme A mutase
Identifiers
Symbol	MUT
Entrez	4594
HUGO	7526
OMIM	609058
RefSeq	NM_000255
UniProt	P22033
Other data
EC number	5.4.99.2
Locus	Chr. 6 p21

Methylmalonyl-Coenzyme A mutase is an enzyme involved in key metabolic pathways. It catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA. It requires its Vitamin B₁₂ derived prosthetic group, adenosylcobalamin, to function.

The substrate of Methylmalonyl-CoA mutase, methylmalonyl-CoA, is primarily derived from propionyl-CoA, a substance formed from the catabolism and digestion of isoleucine, valine, threonine, methionine, thymine, uracil, cholesterol, or odd-chain fatty acids.

The product of the enzyme, succinyl-CoA, is a key molecule of the TCA cycle.

Pathology

A deficiency of this enzyme is responsible for an inherited disorder of metabolism, Methylmalonyl-CoA mutase deficiency, which is one of the causes of methylmalonic acidemia.

Function

MUT resides in the mitochondria where a number of substances, including the branched-chain amino acids Ile and Val, as well as Met, Thr, thymine and odd-chain FAs are metabolized via Methylmalonate semialdehyde (MMlSA) or Propionyl-CoA (Pr-CoA) to a common compound - Methyl-malonyl-CoA (MMl-CoA).

MUT reaction mechanism begins with homolytic cleavage of AdoB12's C-Co(III) bond, the C and Co atoms each acquire one of the electrons that formed the cleaved electron pair bond. The Co ion therefore fluctuates between its Co(III) and Co(II) oxidation states [the two states are spectroscopically distinguishable: Co(III) is red and diamagnetic (no unpaired electrons), whereas Co(II) is yellow and paramagnetic (unpaired electrons)]. Hence, the role of coenzyme B-12 in the catalytic process is that of a reversible free radical generator. The C-Co(III) bond is well suited to this function because it is inherently weak (dissociation energy = 109 kJ/mol) and appears to be further weakened through steric interactions with the enzyme. A homolytic cleavage reaction is unusual in biology; most other biological bond cleavage reactions occur via heterolytic cleavage (in which the electron pair forming the cleaved bond is fully acquired by one of the separating atoms). [2](p.)

External links

• MeSH Methylmalonyl-CoA+Mutase

Template:Isomerase-stub

v • d • e Isomerase: mutases (EC 5.4)
5.4.2 Phosphomutases	Phosphoglycerate mutase - Bisphosphoglycerate mutase - Phosphoglucomutase
5.4.99 Other groups	Methylmalonyl-CoA mutase - Lanosterol synthase

v • d • e Amino acid metabolism enzymes (essential in CAPS)
K	LYSINE→acetyl-CoA Saccharopine dehydrogenase - Glutaryl-CoA dehydrogenase LEUCINE→acetyl-CoA Branched-chain alpha-keto acid dehydrogenase complex - Isovaleryl coenzyme A dehydrogenase - Methylcrotonyl-CoA carboxylase TRYPTOPHAN→acetyl-CoA Kynureninase PHENYLALANINE→tyrosine→acetoacetate (see below)
G	glycine→serine→pyruvate→TCA Serine hydroxymethyltransferase - Serine dehydratase alanine→pyruvate→TCA Alanine transaminase cysteine→pyruvate→TCA D-cysteine desulfhydrase threonine→pyruvate→TCA L-threonine dehydrogenase HISTIDINE→glutamate Histidine ammonia-lyase - Urocanate hydratase - Formiminotransferase cyclodeaminase proline→glutamate Proline oxidase - Pyrroline-5-carboxylate reductase - 1-Pyrroline-5-carboxylate dehydrogenase/ALDH4A1 - PYCR1 arginine→glutamate Ornithine aminotransferase - Ornithine decarboxylase - Agmatinase glutamate→alpha-ketoglutarate→TCA Glutamate dehydrogenase METHIONINE→propionyl-CoA Methionine adenosyltransferase - Adenosylhomocysteinase - (or MTR/Homocysteine methyltransferase) - Cystathionine beta synthase - Cystathionine gamma-lyase ISOLEUCINE/valine→propionyl-CoA Branched-chain alpha-keto acid dehydrogenase complex
NT	HISTIDINE→histamine Histidine decarboxylase tyrosine→dopamine→epinephrine Tyrosine hydroxylase - Aromatic L-amino acid decarboxylase - Dopamine beta hydroxylase - Phenylethanolamine N-methyltransferase - Catechol-O-methyl transferase glutamate→GABA Glutamate decarboxylase arginine→NO Nitric oxide synthase
Other	tyrosine→melanin Tyrosinase TRYPTOPHAN→serotonin→melatonin Tryptophan hydroxylase - Aromatic L-amino acid decarboxylase - Acetylserotonin O-methyltransferase cysteine+glutamate→glutathione Gamma-glutamylcysteine synthetase - Glutathione synthetase glycine→creatine Guanidinoacetate N-methyltransferase - Creatine kinase glutamate→glutamine Glutamine synthetase - Glutaminase collagen Prolyl hydroxylase - Lysyl hydroxylase
see also disorders, intermediates

v • d • e Metabolism: Citric acid cycle enzymes
Cycle	Citrate synthase - Aconitase - Isocitrate dehydrogenase - Oxoglutarate dehydrogenase - Succinyl CoA synthetase Succinate dehydrogenase (SDHA, SDHB, SDHC, SDHD) - Fumarase - Malate dehydrogenase
Anaplerotic	to acetyl-CoA: Pyruvate dehydrogenase complex (regulated by Pyruvate dehydrogenase kinase and Pyruvate dehydrogenase phosphatase) to ketoglutaric acid: Glutamate dehydrogenase to succinyl-CoA: Methylmalonyl-CoA mutase to oxaloacetate: Pyruvate carboxylase - Aspartate transaminase

Acknowledgement and Attribution Regarding Sources of Content

Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .