Biology:Isovaleryl-CoA dehydrogenase

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isovaleryl-CoA dehydrogenase
	Isovaleryl-CoA dehydrogenase tetramer, Human
Identifiers
EC number	1.3.8.4
CAS number	37274-61-6
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
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PMC	articles
PubMed	articles
NCBI	proteins

In enzymology, an isovaleryl-CoA dehydrogenase (EC 1.3.8.4) is an enzyme that catalyzes the chemical reaction

3-methylbutanoyl-CoA + acceptor [math]\displaystyle{ \rightleftharpoons }[/math] 3-methylbut-2-enoyl-CoA + reduced acceptor

Thus, the two substrates of this enzyme are 3-methylbutanoyl-CoA and acceptor, whereas its two products are 3-methylbut-2-enoyl-CoA and reduced acceptor.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-CH group of donor with other acceptors. The systematic name of this enzyme class is 3-methylbutanoyl-CoA:acceptor oxidoreductase. Other names in common use include isovaleryl-coenzyme A dehydrogenase, isovaleroyl-coenzyme A dehydrogenase, and 3-methylbutanoyl-CoA:(acceptor) oxidoreductase. This enzyme participates in valine, leucine and isoleucine degradation. It employs one cofactor, FAD.

Structural studies

As of late 2007, only one structure has been solved for this class of enzymes, with the PDB accession code 1IVH. It was created by a group containing K.A.Tiffany, D.L.Roberts, M.Wang, R.Paschke, A.-W.A.Mohsen, J.Vockley, and J.J.P.Kim. The structure was released on May 20, 1998.Doe. "PDBsum entry: 1ivh". https://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?pdbcode=1IVH/.

Leucine metabolism

Leucine metabolism in humans

L-Leucine

Branched-chain amino
acid aminotransferase

Muscle: α-Ketoisocaproate (α-KIC)

Liver: α-Ketoisocaproate (α-KIC)

Branched-chain α-ketoacid
dehydrogenase (mitochondria)

KIC-dioxygenase
(cytosol)

Isovaleryl-CoA

β-Hydroxy
β-methylbutyrate
(HMB)

Excreted
in urine
(10–40%)

HMB-CoA

β-Hydroxy β-methylglutaryl-CoA
(HMG-CoA)

β-Methylcrotonyl-CoA
(MC-CoA)

β-Methylglutaconyl-CoA
(MG-CoA)

CO₂

O₂

CO₂

H₂O

CO₂

H₂O

(liver)
HMG-CoA
lyase

Enoyl-CoA hydratase

Isovaleryl-CoA
dehydrogenase

β-Hydroxybutyrate
dehydrogenase

Unknown
enzyme

Human metabolic pathway for HMB and isovaleryl-CoA relative to L-leucine.^[1]^[2]^[3] Of the two major pathways, L-leucine is mostly metabolized into isovaleryl-CoA, while only about 5% is metabolized into HMB.^[1]^[2]^[3]

References

↑ ^1.0 ^1.1 "International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB)". Journal of the International Society of Sports Nutrition 10 (1): 6. February 2013. doi:10.1186/1550-2783-10-6. PMID 23374455.
↑ ^2.0 ^2.1 "HMB supplementation: clinical and athletic performance-related effects and mechanisms of action". Amino Acids 40 (4): 1015–1025. April 2011. doi:10.1007/s00726-010-0678-0. PMID 20607321. "HMB is a metabolite of the amino acid leucine (Van Koverin and Nissen 1992), an essential amino acid. The first step in HMB metabolism is the reversible transamination of leucine to [α-KIC] that occurs mainly extrahepatically (Block and Buse 1990). Following this enzymatic reaction, [α-KIC] may follow one of two pathways. In the first, HMB is produced from [α-KIC] by the cytosolic enzyme KIC dioxygenase (Sabourin and Bieber 1983). The cytosolic dioxygenase has been characterized extensively and differs from the mitochondrial form in that the dioxygenase enzyme is a cytosolic enzyme, whereas the dehydrogenase enzyme is found exclusively in the mitochondrion (Sabourin and Bieber 1981, 1983). Importantly, this route of HMB formation is direct and completely dependent of liver KIC dioxygenase. Following this pathway, HMB in the cytosol is first converted to cytosolic β-hydroxy-β-methylglutaryl-CoA (HMG-CoA), which can then be directed for cholesterol synthesis (Rudney 1957) (Fig. 1). In fact, numerous biochemical studies have shown that HMB is a precursor of cholesterol (Zabin and Bloch 1951; Nissen et al. 2000).".
↑ ^3.0 ^3.1 Nutrient Metabolism: Structures, Functions, and Genes (2nd ed.). Academic Press. May 2015. pp. 385–388. ISBN 978-0-12-387784-0. https://books.google.com/books?id=aTQTAAAAQBAJ&printsec=frontcover#v=onepage. Retrieved 6 June 2016. "Energy fuel: Eventually, most Leu is broken down, providing about 6.0kcal/g. About 60% of ingested Leu is oxidized within a few hours ... Ketogenesis: A significant proportion (40% of an ingested dose) is converted into acetyl-CoA and thereby contributes to the synthesis of ketones, steroids, fatty acids, and other compounds"
Figure 8.57: Metabolism of L-leucine

"Enzymatic carboxylation of beta-hydroxyisovaleryl coenzyme A". J. Biol. Chem. 219 (2): 539–50. 1956. doi:10.1016/S0021-9258(18)65714-X. PMID 13319276.
"Purification and characterization of isovaleryl coenzyme A dehydrogenase from rat liver mitochondria". J. Biol. Chem. 258 (2): 1077–85. 1983. doi:10.1016/S0021-9258(18)33161-2. PMID 6401713.
"Isovaleric acidemia: a new genetic defect of leucine metabolism". Proc. Natl. Acad. Sci. U.S.A. 56 (1): 236–42. 1966. doi:10.1073/pnas.56.1.236. PMID 5229850. Bibcode: 1966PNAS...56..236T.

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Original source: https://en.wikipedia.org/wiki/Isovaleryl-CoA dehydrogenase. Read more

[ISSN_position_stand_2013-1] 1.0 ^1.1 "International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB)". Journal of the International Society of Sports Nutrition 10 (1): 6. February 2013. doi:10.1186/1550-2783-10-6. PMID 23374455.

[HMB_athletic_performance-related_effects_2011_review-2] 2.0 ^2.1 "HMB supplementation: clinical and athletic performance-related effects and mechanisms of action". Amino Acids 40 (4): 1015–1025. April 2011. doi:10.1007/s00726-010-0678-0. PMID 20607321. "HMB is a metabolite of the amino acid leucine (Van Koverin and Nissen 1992), an essential amino acid. The first step in HMB metabolism is the reversible transamination of leucine to [α-KIC] that occurs mainly extrahepatically (Block and Buse 1990). Following this enzymatic reaction, [α-KIC] may follow one of two pathways. In the first, HMB is produced from [α-KIC] by the cytosolic enzyme KIC dioxygenase (Sabourin and Bieber 1983). The cytosolic dioxygenase has been characterized extensively and differs from the mitochondrial form in that the dioxygenase enzyme is a cytosolic enzyme, whereas the dehydrogenase enzyme is found exclusively in the mitochondrion (Sabourin and Bieber 1981, 1983). Importantly, this route of HMB formation is direct and completely dependent of liver KIC dioxygenase. Following this pathway, HMB in the cytosol is first converted to cytosolic β-hydroxy-β-methylglutaryl-CoA (HMG-CoA), which can then be directed for cholesterol synthesis (Rudney 1957) (Fig. 1). In fact, numerous biochemical studies have shown that HMB is a precursor of cholesterol (Zabin and Bloch 1951; Nissen et al. 2000).".

[Leucine_metabolism-3] 3.0 ^3.1 Nutrient Metabolism: Structures, Functions, and Genes (2nd ed.). Academic Press. May 2015. pp. 385–388. ISBN 978-0-12-387784-0. https://books.google.com/books?id=aTQTAAAAQBAJ&printsec=frontcover#v=onepage. Retrieved 6 June 2016. "Energy fuel: Eventually, most Leu is broken down, providing about 6.0kcal/g. About 60% of ingested Leu is oxidized within a few hours ... Ketogenesis: A significant proportion (40% of an ingested dose) is converted into acetyl-CoA and thereby contributes to the synthesis of ketones, steroids, fatty acids, and other compounds"
Figure 8.57: Metabolism of L-leucine

[1]

[2]

[3]

v t e Oxidoreductases: CH–CH oxidoreductases (EC 1.3)
1.3.1: NAD/NADP acceptor	Enoyl-acyl carrier protein reductase/Enoyl ACP reductase 7-Dehydrocholesterol reductase Biliverdin reductase 2,4 Dienoyl-CoA reductase Dihydroxymethyloxo-tetrahydroquinoline dehydrogenase
1.3.3: Oxygen acceptor	Dihydroorotate dehydrogenase Coproporphyrinogen III oxidase Protoporphyrinogen oxidase Bilirubin oxidase Acyl-CoA oxidase Dihydrouracil oxidase Tetrahydroberberine oxidase Secologanin synthase Tryptophan alpha,beta-oxidase Pyrroloquinoline-quinone synthase L-galactonolactone oxidase
1.3.5: Quinone	Succinate dehydrogenase SDHA SDHB SDHC SDHD
1.3.99: Other acceptors	Fumarate reductase Butyryl-CoA dehydrogenase Acyl CoA dehydrogenase ACADSB ACADS 5α-reductase SRD5A1 SRD5A2 SRD5A3 Glutaryl-CoA dehydrogenase Isovaleryl coenzyme A dehydrogenase 3-oxo-5beta-steroid 4-dehydrogenase

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

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