Literature summary for 4.2.1.17 extracted from

Bedoyan, J.K.; Yang, S.P.; Ferdinandusse, S.; Jack, R.M.; Miron, A.; Grahame, G.; DeBrosse, S.D.; Hoppel, C.L.; Kerr, D.S.; Wanders, R.J.A.
Lethal neonatal case and review of primary short-chain enoyl-CoA hydratase (SCEH) deficiency associated with secondary lymphocyte pyruvate dehydrogenase complex (PDC) deficiency (2017), Mol. Genet. Metab., 120, 342-349 .

Search for more literature for 4.2.1.17

Cloned(Commentary)

Cloned (Comment)	Organism
gene ECHS1, located on chromosome 10, genotyping	Homo sapiens

Protein Variants

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

Localization	Comment	Organism	GeneOntology No.	Textmining
mitochondrion	-	Homo sapiens	5739	-

Natural Substrates/ Products (Substrates)

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

Organism	UniProt	Comment	Textmining
Homo sapiens	P30084	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
fibroblast	-	Homo sapiens	-

Substrates and Products (Substrate)

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

Synonyms	Comment	Organism
ECHS1	-	Homo sapiens
SCEH	-	Homo sapiens
short-chain enoyl-CoA hydratase	-	Homo sapiens

General Information

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

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Release 2023.1 (January 2023)