Cloned (Comment) | Organism |
---|---|
gene ECHS1, located on chromosome 10, genotyping | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
A3D/F279S | naturally occuring mutations, identification of heterozygous ECHS1 mutations c.836T>C (novel) (p.F279S) and and c.8C>A (p.A3D) identified by whole exome sequencing, lethal neonatal case. SCEH deficiency is confirmed with very low SCEH activity in fibroblasts and nearly absent immunoreactivity of SCEH. The patient has a severe neonatal course with elevated blood and cerebrospinal fluid (CSF) lactate and pyruvate concentrations, high plasma alanine and slightly low plasma cystine. 2-Methyl-2,3-dihydroxybutyric acid is markedly elevated as are metabolites of the three branched-chain ketoacids on urine organic acids analysis. These urine metabolites notably decrease when lactic acidosis decreases in blood. Lymphocyte pyruvate dehydrogenase complex (PDC) activity is deficient, but PDC and 2-oxoglutarate dehydrogenase complex activities in cultured fibroblasts are normal. Oxidative phosphorylation analysis on intact digitonin-permeabilized fibroblasts is suggestive of slightly reduced PDC activity relative to control range in mitochondria | Homo sapiens |
L230F | naturally occuring mutation | Homo sapiens |
additional information | review of other cases of mutations with primary short-chain enoyl-CoA hydratase (SCEH) deficiency associated with secondary lymphocyte pyruvate dehydrogenase complex (PDC) deficiency, overview | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
mitochondrion | - |
Homo sapiens | 5739 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
crotonyl-CoA + H2O | Homo sapiens | - |
(3S)-hydroxybutyryl-CoA | - |
r | |
additional information | Homo sapiens | human SCEH has broad substrate specificity for acyl-CoAs, including crotonyl-CoA (from beta-oxidation), acryloyl-CoA (from metabolism of various amino acids), 3-methylcrotonyl-CoA (from leucine metabolism), tiglyl-CoA (from isoleucine metabolism), and methacrylyl-CoA (from valine metabolism). Although SCEH binds tiglyl-CoA, the rate of hydration is relatively low | ? | - |
? | |
tiglyl-CoA + H2O | Homo sapiens | low activity | 3-hydroxy-2-methylbutanoyl-CoA | - |
r |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P30084 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
fibroblast | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
crotonyl-CoA + H2O | - |
Homo sapiens | (3S)-hydroxybutyryl-CoA | - |
r | |
additional information | human SCEH has broad substrate specificity for acyl-CoAs, including crotonyl-CoA (from beta-oxidation), acryloyl-CoA (from metabolism of various amino acids), 3-methylcrotonyl-CoA (from leucine metabolism), tiglyl-CoA (from isoleucine metabolism), and methacrylyl-CoA (from valine metabolism). Although SCEH binds tiglyl-CoA, the rate of hydration is relatively low | Homo sapiens | ? | - |
? | |
tiglyl-CoA + H2O | low activity | Homo sapiens | 3-hydroxy-2-methylbutanoyl-CoA | - |
r |
Synonyms | Comment | Organism |
---|---|---|
ECHS1 | - |
Homo sapiens |
SCEH | - |
Homo sapiens |
short-chain enoyl-CoA hydratase | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | mutations in ECHS1 result in short-chain enoyl-CoA hydratase (SCEH) deficiency which mainly affects the catabolism of various amino acids, particularly valine. Patients show a Leigh syndrome-like phenotype, important diagnostic markers for this disorder include S-(2-carboxypropyl)-L-cysteine and S-(2-carboxypropyl)cysteamine (which are derived from methacrylyl-CoA), S-(2-carboxyethyl)-L-cysteine and S-(2-carboxyethyl)cysteamine (which are derived from acryloyl-CoA), and 2-methyl-2,3-dihydroxybutyric acid (MDHB). In a lethal neonatal case, SCEH deficiency is confirmed with very low SCEH activity in fibroblasts and nearly absent immunoreactivity of SCEH. The patient has a severe neonatal course with elevated blood and cerebrospinal fluid (CSF) lactate and pyruvate concentrations, high plasma alanine and slightly low plasma cystine. 2-Methyl-2,3-dihydroxybutyric acid is markedly elevated as are metabolites of the three branched-chain ketoacids on urine organic acids analysis. These urine metabolites notably decrease when lactic acidosis decreases in blood. Lymphocyte pyruvate dehydrogenase complex (PDC) activity is deficient, but PDC and 2-oxoglutarate dehydrogenase complex activities in cultured fibroblasts are normal. Oxidative phosphorylation analysis on intact digitonin-permeabilized fibroblasts is suggestive of slightly reduced PDC activity relative to control range in mitochondria. Review of other cases of mutations with primary short-chain enoyl-CoA hydratase (SCEH) deficiency associated with secondary lymphocyte pyruvate dehydrogenase complex (PDC) deficiency, about half of cases with primary SCEH deficiency also exhibit secondary PDC deficiency, overview. To date, almost half of cases diagnosed with this autosomal recessive disorder perish within the neonatal or infantile period, but survival into adulthood is reported | Homo sapiens |