HMGCS2

Last updated
HMGCS2
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases HMGCS2 , 3-hydroxy-3-methylglutaryl-CoA synthase 2
External IDs OMIM: 600234 MGI: 101939 HomoloGene: 38066 GeneCards: HMGCS2
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001166107
NM_005518

NM_008256

RefSeq (protein)

NP_001159579
NP_005509

NP_032282

Location (UCSC) Chr 1: 119.75 – 119.77 Mb Chr 3: 98.19 – 98.22 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial) is an enzyme in humans that is encoded by the HMGCS2 gene. [5]

Contents

The protein encoded by this gene belongs to the HMG-CoA synthase family. It is a mitochondrial enzyme that catalyzes the second and rate-limiting reaction of ketogenesis, a metabolic pathway that provides lipid-derived energy for various organs during times of carbohydrate deprivation, such as fasting, by addition of a third acetyl group to acetoacetyl-CoA, producing HMG-CoA. [6] Mutations in this gene are associated with HMG-CoA synthase deficiency [7] (also known as HMGCS2D), affecting ketone body synthesis.

Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [5]

Occurrence

HMGCS2 is not found in cetaceans, elephantids, or Old World fruit bats. [8]

Related Research Articles

<span class="mw-page-title-main">HMG-CoA reductase</span> Mammalian protein found in Homo sapiens

HMG-CoA reductase is the rate-controlling enzyme of the mevalonate pathway, the metabolic pathway that produces cholesterol and other isoprenoids. HMGCR catalyzes the conversion of HMG-CoA to mevalonic acid, a necessary step in the biosynthesis of cholesterol. Normally in mammalian cells this enzyme is competitively suppressed so that its effect is controlled. This enzyme is the target of the widely available cholesterol-lowering drugs known collectively as the statins, which help treat dyslipidemia.

<span class="mw-page-title-main">3-Hydroxy-3-methylglutaryl-CoA lyase deficiency</span> Medical condition

3-Hydroxy-3-methylglutaryl-CoA lyase deficiency is an uncommon inherited disorder in which the body cannot properly process the amino acid leucine. Additionally, the disorder prevents the body from making ketones, which are used for energy during fasting.

<span class="mw-page-title-main">ACADVL</span> Protein-coding gene in the species Homo sapiens

Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (VLCAD) is an enzyme that in humans is encoded by the ACADVL gene.

<span class="mw-page-title-main">HMG-CoA</span> Chemical compound

β-Hydroxy β-methylglutaryl-CoA (HMG-CoA), also known as 3-hydroxy-3-methylglutaryl coenzyme A, is an intermediate in the mevalonate and ketogenesis pathways. It is formed from acetyl CoA and acetoacetyl CoA by HMG-CoA synthase. The research of Minor J. Coon and Bimal Kumar Bachhawat in the 1950s at University of Illinois led to its discovery.

Methylcrotonyl CoA carboxylase is a biotin-requiring enzyme located in the mitochondria. MCC uses bicarbonate as a carboxyl group source to catalyze the carboxylation of a carbon adjacent to a carbonyl group performing the fourth step in processing leucine, an essential amino acid.

<span class="mw-page-title-main">Acetolactate synthase</span> Class of enzymes

The acetolactate synthase (ALS) enzyme is a protein found in plants and micro-organisms. ALS catalyzes the first step in the synthesis of the branched-chain amino acids.

<span class="mw-page-title-main">3-Hydroxy-3-methylglutaryl-CoA lyase</span> Class of enzymes

3-Hydroxy-3-methylglutaryl-CoA lyase is an enzyme (EC 4.1.3.4 that in human is encoded by the HMGCL gene located on chromosome 1. It is a key enzyme in ketogenesis. It is a ketogenic enzyme in the liver that catalyzes the formation of acetoacetate from HMG-CoA within the mitochondria. It also plays a prominent role in the catabolism of the amino acid leucine.

<span class="mw-page-title-main">Acetoacetyl-CoA</span> Chemical compound

Acetoacetyl CoA is the precursor of HMG-CoA in the mevalonate pathway, which is essential for cholesterol biosynthesis. It also takes a similar role in the ketone bodies synthesis (ketogenesis) pathway of the liver. In the ketone bodies digestion pathway, it is no longer associated with having HMG-CoA as a product or as a reactant.

<span class="mw-page-title-main">Methylcrotonyl-CoA</span> Chemical compound

3-Methylcrotonyl-CoA or β-Methylcrotonyl-CoA is an intermediate in the metabolism of leucine.

<span class="mw-page-title-main">Methylglutaconyl-CoA hydratase</span> Protein-coding gene in the species Homo sapiens

3-Methylglutaconyl-CoA hydratase, also known as MG-CoA hydratase and AUH, is an enzyme encoded by the AUH gene on chromosome 19. It is a member of the enoyl-CoA hydratase/isomerase superfamily, but it is the only member of that family that is able to bind to RNA. Not only does it bind to RNA, AUH has also been observed to be involved in the metabolic enzymatic activity, making it a dual-role protein. Mutations of this gene have been found to cause a disease called 3-Methylglutaconic Acuduria Type 1.

<span class="mw-page-title-main">Hydroxymethylglutaryl-CoA synthase</span> Class of enzymes

In molecular biology, hydroxymethylglutaryl-CoA synthase or HMG-CoA synthase EC 2.3.3.10 is an enzyme which catalyzes the reaction in which acetyl-CoA condenses with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). This reaction comprises the second step in the mevalonate-dependent isoprenoid biosynthesis pathway. HMG-CoA is an intermediate in both cholesterol synthesis and ketogenesis. This reaction is overactivated in patients with diabetes mellitus type 1 if left untreated, due to prolonged insulin deficiency and the exhaustion of substrates for gluconeogenesis and the TCA cycle, notably oxaloacetate. This results in shunting of excess acetyl-CoA into the ketone synthesis pathway via HMG-CoA, leading to the development of diabetic ketoacidosis.

<span class="mw-page-title-main">Aldehyde dehydrogenase 4 family, member A1</span> Protein-coding gene in the species Homo sapiens

Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the ALDH4A1 gene.

<span class="mw-page-title-main">HCCS (gene)</span> Protein-coding gene in the species Homo sapiens

Cytochrome c-type heme lyase is an enzyme that in humans is encoded by the HCCS gene on chromosome X.

<span class="mw-page-title-main">Aldehyde dehydrogenase 18 family, member A1</span> Protein-coding gene in the species Homo sapiens

Delta-1-pyrroline-5-carboxylate synthetase (P5CS) is an enzyme that in humans is encoded by the ALDH18A1 gene. This gene is a member of the aldehyde dehydrogenase family and encodes a bifunctional ATP- and NADPH-dependent mitochondrial enzyme with both gamma-glutamyl kinase and gamma-glutamyl phosphate reductase activities. The encoded protein catalyzes the reduction of glutamate to delta1-pyrroline-5-carboxylate, a critical step in the de novo biosynthesis of proline, ornithine and arginine. Mutations in this gene lead to hyperammonemia, hypoornithinemia, hypocitrullinemia, hypoargininemia and hypoprolinemia and may be associated with neurodegeneration, cataracts and connective tissue diseases. Alternatively spliced transcript variants, encoding different isoforms, have been described for this gene. As reported by Bruno Reversade and colleagues, ALDH18A1 deficiency or dominant-negative mutations in P5CS in humans causes a progeroid disease known as De Barsy Syndrome.

<span class="mw-page-title-main">SUCLG1</span>

Succinyl-CoA ligase [GDP-forming] subunit alpha, mitochondrial is an enzyme that in humans is encoded by the SUCLG1 gene.

<span class="mw-page-title-main">Alpha-aminoadipic semialdehyde synthase</span>

Alpha-aminoadipic semialdehyde synthase is an enzyme encoded by the AASS gene in humans and is involved in their major lysine degradation pathway. It is similar to the separate enzymes coded for by the LYS1 and LYS9 genes in yeast, and related to, although not similar in structure, the bifunctional enzyme found in plants. In humans, mutations in the AASS gene, and the corresponding alpha-aminoadipic semialdehyde synthase enzyme are associated with familial hyperlysinemia. This condition is inherited in an autosomal recessive pattern and is not considered a particularly negative condition, thus making it a rare disease.

<span class="mw-page-title-main">CTPS2</span> Protein-coding gene in the species Homo sapiens

CTP synthase 2 is an enzyme that in humans is encoded by the CTPS2 gene.

<span class="mw-page-title-main">MTHFD2L</span> Protein-coding gene in the species Homo sapiens

NAD-dependent methylenetetrahydrofolate dehydrogenase 2-like protein (MTHFD2L), also known as bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, is an enzyme that in humans is encoded by the MTHFD2L gene on chromosome 4. This enzyme localizes to the inner mitochondrial membrane, where it performs the NADP+-dependent dehydrogenase/cyclohydrolase activity as part of the mitochondrial pathway to convert folate to formate. It is associated with fluctuations in cytokine secretion in response to viral infections and vaccines.

<span class="mw-page-title-main">PCK2</span>

Phosphoenolpyruvate carboxykinase 2, mitochondrial, is an isozyme of phosphoenolpyruvate carboxykinase that in humans is encoded by the PCK2 gene on chromosome 14. This gene encodes a mitochondrial enzyme that catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP) in the presence of guanosine triphosphate (GTP). A cytosolic form of this protein is encoded by a different gene and is the key enzyme of gluconeogenesis in the liver. Alternatively spliced transcript variants have been described.[provided by RefSeq, Apr 2014]

<span class="mw-page-title-main">SUCLG2</span>

Succinyl-CoA ligase [GDP-forming] subunit beta, mitochondrial is an enzyme that in humans is encoded by the SUCLG2 gene on chromosome 3.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000134240 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000027875 - 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. 1 2 "Entrez Gene: 3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial)".
  6. Drabbe S, Pelzer A, Slenter D, Willighagen E. "Disorders in ketone body synthesis (Homo sapiens)". Wiki Pathways.
  7. Aledo R, Mir C, Dalton RN, Turner C, Pié J, Hegardt FG, et al. (February 2006). "Refining the diagnosis of mitochondrial HMG-CoA synthase deficiency". Journal of Inherited Metabolic Disease. 29 (1): 207–211. doi:10.1007/s10545-006-0214-2. PMID   16601895. S2CID   24866271.
  8. Jebb D, Hiller M (October 2018). "Recurrent loss of HMGCS2 shows that ketogenesis is not essential for the evolution of large mammalian brains". eLife. 7: e38906. doi:10.7554/eLife.38906. PMC   6191284 . PMID   30322448.