Isovaleryl-CoA dehydrogenase

isovaleryl-CoA dehydrogenase
Isovaleryl-CoA dehydrogenase tetramer, Human
Identifiers
EC no.	1.3.8.4
CAS no.	37274-61-6
Databases
BRENDA	enzyme data
ExPASy	NiceZyme view
KEGG	enzyme entry
MetaCyc	metabolic pathway
Rhea	reactions
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

IVD
Identifiers
Aliases	IVD , IVDH, ACAD2, isovaleryl-CoA dehydrogenase
External IDs	OMIM: 607036; MGI: 1929242; GeneCards: IVD
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1IVH
Enzyme activity EC # BRENDA ExPASy KEGG MetaCyc 1.3.8.1 ↗ ↗ ↗ ↗ 1.3.8.4 ↗ ↗ ↗ ↗
Gene location (Human) Chr. Chromosome 15 (human) [1] Band 15q15.1 Start 40,405,485 bp [1] End 40,435,947 bp [1]
Gene location (Mouse) Chr. Chromosome 2 (mouse) [2] Band 2|2 E5 Start 118,692,435 bp [2] End 118,713,390 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of thyroid gland left lobe of thyroid gland right lobe of liver right adrenal cortex anterior pituitary left adrenal gland left adrenal cortex right ovary left ovary muscle of thigh Top expressed in neural layer of retina right kidney interventricular septum right ventricle myocardium of ventricle cardiac muscles proximal tubule cardiac muscle tissue of left ventricle human kidney muscle of thigh More reference expression data BioGPS n/a
Gene ontology Molecular function oxidoreductase activity, acting on the CH-CH group of donors oxidoreductase activity acyl-CoA dehydrogenase activity flavin adenine dinucleotide binding isovaleryl-CoA dehydrogenase activity protein binding Cellular component mitochondrial matrix mitochondrion Biological process branched-chain amino acid catabolic process leucine catabolic process fatty acid beta-oxidation using acyl-CoA dehydrogenase Sources:Amigo / QuickGO
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse Entrez 3712 56357 Ensembl ENSG00000128928 ENSMUSG00000027332 UniProt P26440 Q9JHI5 RefSeq (mRNA) NM_001159508 NM_002225 NM_001354597 NM_001354598 NM_001354599 NM_001354600 NM_001354601 NM_019826 RefSeq (protein) NP_001152980 NP_002216 NP_001341526 NP_001341527 NP_001341528 NP_001341529 NP_001341530 NP_062800 Location (UCSC) Chr 15: 40.41 – 40.44 Mb Chr 2: 118.69 – 118.71 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Isovaleryl-CoA dehydrogenase (EC 1.3.8.4) is an enzyme that in humans is encoded by the gene IVD. More generally, it refers to any enzyme that catalyzes the chemical reaction

3-methylbutanoyl-CoA + acceptor 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 PDB: 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" . Retrieved November 25, 2019.

Leucine metabolism

Leucine metabolism in humans L-Leucine Branched-chain amino acid aminotransferase α-Ketoglutarate Glutamate Glutamate Alanine Pyruvate 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 CO2 O2 CO2 H2O CO2 H2O (liver) HMG-CoA lyase Enoyl-CoA hydratase Isovaleryl-CoA dehydrogenase MC-CoA carboxylase MG-CoA hydratase HMG-CoA reductase HMG-CoA  synthase β-Hydroxybutyrate dehydrogenase Mevalonate pathway Thiolase Unknown enzyme β-Hydroxybutyrate Acetoacetyl-CoA Acetyl-CoA Acetoacetate Mevalonate Cholesterol Human metabolic pathway for HMB and isovaleryl-CoA relative to L-leucine. [5] [6] [7] Of the two major pathways, L-leucine is mostly metabolized into isovaleryl-CoA, while only about 5% is metabolized into HMB. [5] [6] [7]

References

1. GRCh38: Ensembl release 89: ENSG00000128928 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027332 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Wilson JM, Fitschen PJ, Campbell B, Wilson GJ, Zanchi N, Taylor L, Wilborn C, Kalman DS, Stout JR, Hoffman JR, Ziegenfuss TN, Lopez HL, Kreider RB, Smith-Ryan AE, Antonio J (February 2013). "International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB)". Journal of the International Society of Sports Nutrition. 10 (1): 6. doi: 10.1186/1550-2783-10-6 . PMC   3568064 . PMID   23374455.
6. Zanchi NE, Gerlinger-Romero F, Guimarães-Ferreira L, de Siqueira Filho MA, Felitti V, Lira FS, Seelaender M, Lancha AH (April 2011). "HMB supplementation: clinical and athletic performance-related effects and mechanisms of action". Amino Acids. 40 (4): 1015–1025. doi:10.1007/s00726-010-0678-0. PMID   20607321. S2CID   11120110. 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).
7. Kohlmeier M (May 2015). "Leucine". Nutrient Metabolism: Structures, Functions, and Genes (2nd ed.). Academic Press. pp. 385–388. ISBN   978-0-12-387784-0 . 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

• BACHHAWAT BK, ROBINSON WG, COON MJ (1956). "Enzymatic carboxylation of beta-hydroxyisovaleryl coenzyme A". J. Biol. Chem. 219 (2): 539–50. doi: 10.1016/S0021-9258(18)65714-X . PMID   13319276.
• Ikeda Y, Tanaka K (1983). "Purification and characterization of isovaleryl coenzyme A dehydrogenase from rat liver mitochondria". J. Biol. Chem. 258 (2): 1077–85. doi: 10.1016/S0021-9258(18)33161-2 . PMID   6401713.
• Tanaka K, Budd MA, Efron ML, Isselbacher KJ (1966). "Isovaleric acidemia: a new genetic defect of leucine metabolism". Proc. Natl. Acad. Sci. U.S.A. 56 (1): 236–42. Bibcode:1966PNAS...56..236T. doi: 10.1073/pnas.56.1.236 . PMC   285701 . PMID   5229850.