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Information on EC 1.1.1.35 - 3-hydroxyacyl-CoA dehydrogenase and Organism(s) Homo sapiens
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1.1.1.35 3-hydroxyacyl-CoA dehydrogenaseIUBMB Comments
Also oxidizes S-3-hydroxyacyl-N-acylthioethanolamine and S-3-hydroxyacyl-hydrolipoate. Some enzymes act, more slowly, with NADP+. Broad specificity to acyl chain-length (cf. EC 1.1.1.211 [long-chain-3-hydroxyacyl-CoA dehydrogenase]).
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Word Map
- 1.1.1.35
- citrate
- acyl-coas
- peroxisomal
-
thiolase
- carnitine
-
trifunctional
-
phosphofructokinase
- hexokinase
-
endurance
-
vastus
- lateralis
- acetoacetyl-coa
-
medium-chain
- soleus
- hypoglycemia
-
extensor
- lchad
- acylcarnitines
- hyperinsulinism
-
2-enoyl-coa
-
fast-twitch
-
plantaris
-
2,4-dienoyl-coa
-
schulz
- crotonase
-
hypoketotic
-
4.1.3.7
-
glyoxysomes
-
hellp
- 3-oxoacyl-coa
-
hydroxyacyl-coas
- trans-2-enoyl-coa
- gluteus
- medicine
- biofuel production
- diagnostics
- pharmacology
- synthesis
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Synonyms
3-hydroxyacyl-coa dehydrogenase, l-3-hydroxyacyl-coa dehydrogenase, beta-hydroxyacyl coa dehydrogenase, hadhsc, 3-hydroxyacyl-coenzyme a dehydrogenase, short-chain 3-hydroxyacyl-coa dehydrogenase, short-chain l-3-hydroxyacyl-coa dehydrogenase, 3-ketoacyl-coa reductase, beta-ketoacyl-coa reductase, fadb2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
1-specific DPN-linked beta-hydroxybutyric dehydrogenase
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-
-
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3-hydroxyacetyl-coenzyme A dehydrogenase
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-
-
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3-hydroxyacyl coenzyme A dehydrogenase
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-
-
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3-hydroxyisobutyryl-CoA dehydrogenase
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-
-
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3-keto reductase
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-
-
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3-L-hydroxyacyl-CoA dehydrogenase
-
-
-
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3-L-hydroxybutyryl-CoA dehydrogenase
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-
-
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3beta-hydroxyacyl coenzyme A dehydrogenase
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-
-
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beta hydroxyacyl dehydrogenase
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-
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beta-hydroxy acid dehydrogenase
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-
-
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beta-hydroxyacyl CoA dehydrogenase
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-
-
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beta-hydroxyacyl-coenzyme A synthetase
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-
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beta-hydroxybutyrylcoenzyme A dehydrogenase
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-
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beta-keto-reductase
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-
-
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beta-ketoacyl-CoA reductase
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-
-
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betahydroxyacylcoenzyme A dehydrogenase
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-
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endoplasmic reticulum-associated amyloid beta-peptide binding protein
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-
-
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HADH
HCDH
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-
-
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L-3-hydroxyacyl CoA dehydrogenase
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-
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L-3-hydroxyacyl-CoA dehydrogenase
L-3-hydroxyacylcoenzyme A dehydrogenase
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-
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SCHAD
Scully protein
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-
-
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short chain L-3-hydroxyacyl-CoA dehydrogenase
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displays optimal activity using 6-carbon substrates
type II HADH
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-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(S)-3-hydroxyacyl-CoA + NAD+ = 3-oxoacyl-CoA + NADH + H+
structure-function analysis and catalytic mechanism, overview
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
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-
-
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redox reaction
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-
-
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reduction
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PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
Benzoate degradation, Biosynthesis of secondary metabolites, Butanoate metabolism, Caprolactam degradation, Carbon fixation pathways in prokaryotes, Fatty acid degradation, Fatty acid elongation, Geraniol degradation, Lysine degradation, Microbial metabolism in diverse environments, Toluene degradation, Tryptophan metabolism, Valine, leucine and isoleucine degradation
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-, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
(S)-3-hydroxyacyl-CoA:NAD+ oxidoreductase
Also oxidizes S-3-hydroxyacyl-N-acylthioethanolamine and S-3-hydroxyacyl-hydrolipoate. Some enzymes act, more slowly, with NADP+. Broad specificity to acyl chain-length (cf. EC 1.1.1.211 [long-chain-3-hydroxyacyl-CoA dehydrogenase]).
CAS REGISTRY NUMBER
COMMENTARY
9028-40-4
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
1-propanol + NAD+
n-propanal + NADH
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multifunctional enzyme from brain
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ir
2-propanol + NAD+
acetone + NADH
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multifunctional enzyme from brain
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ir
3-ketohexadecanoyl-CoA + NADH
(S)-3-hydroxhexadecanoyl-CoA + NAD+
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-
r
5alpha-dihydrotestosterone + NADH
(3beta,5alpha,17beta)-androstane-3,17-diol + NAD+
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-
-
r
(S)-3-hydroxyacyl-CoA + NAD+
3-oxoacyl-CoA + NADH + H+
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the enzyme is involved in fatty acid beta-oxidation in beta cells, overview
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-
?
17beta-estradiol + NAD+
estrone + NADH + H+
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enzyme from brain contains 17beta-hydroxysteroid and 3alpha-hydroxysteroid dehydrogenase activity
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ir
17beta-estradiol + NAD+
estrone + NADH + H+
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enzyme conatains 17beta-hydroxysteroid and 3alpha-hydroxysteroid dehydrogenase activity
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ir
5alpha-androstane-3,17-diol + NAD+
5alpha-dihydrotestosterone + NADH
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inactivation
-
-
?
additional information
?
-
the enzyme is essentially involved in mitochondrial fatty acid beta-oxidation by catalyzing straight chain 3-hydroxyacyl-CoAs, the enzyme plays a role in Alzheimer's disease and Parkinson's disease, overview
-
-
?
additional information
?
-
-
the enzyme is essentially involved in mitochondrial fatty acid beta-oxidation by catalyzing straight chain 3-hydroxyacyl-CoAs, the enzyme plays a role in Alzheimer's disease and Parkinson's disease, overview
-
-
?
additional information
?
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-
the enzyme is involved in intracrinology and is essential for the metabolism of isoleucine and branched-chain fatty acids
-
-
?
additional information
?
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-
the enzyme is involved in the penultimate step in mitochondrial fatty acid oxidation and in development of type 2 diabetes
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-
?
additional information
?
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short-chain L-3-hydroxyacyl-CoA dehydrogenase shows a wide substrate spectrum including cholic acids, steroids, and fatty acids with a preference for short-chain methyl-branched acyl-CoAs, SCHAD might be identical with 17beta-hydroxysteroid dehyxrogenase in human mitochondria, overview
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-
?
additional information
?
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-
short-chain L-3-hydroxyacyl-CoA dehydrogenase shows a wide substrate spectrum including cholic acids, steroids, and fatty acids with a preference for short-chain methyl-branched acyl-CoAs, SCHAD might be identical with 17beta-hydroxysteroid dehyxrogenase in human mitochondria, overview
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-
?
additional information
?
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HADH gene with a novel homozygous missense mutation M188V. Mutations in the HADH gene are associated with significantly decreased short-chain L-HADH activity, mildly decreased medium- and long-chain L-HADH activity, protein-induced hyperinsulinemic hypoglycemia. Patients with hyperinsulinemic hypoglycemia due to HADH gene mutations may have normal acylcarnitines and urine organic acids
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
5alpha-androstane-3,17-diol + NAD+
5alpha-dihydrotestosterone + NADH
-
inactivation
-
-
?
(S)-3-hydroxyacyl-CoA + NAD+
3-oxoacyl-CoA + NADH + H+
-
the enzyme is involved in fatty acid beta-oxidation in beta cells, overview
-
-
?
17beta-estradiol + NAD+
estrone + NADH + H+
-
enzyme conatains 17beta-hydroxysteroid and 3alpha-hydroxysteroid dehydrogenase activity
-
ir
additional information
?
-
the enzyme is essentially involved in mitochondrial fatty acid beta-oxidation by catalyzing straight chain 3-hydroxyacyl-CoAs, the enzyme plays a role in Alzheimer's disease and Parkinson's disease, overview
-
-
?
additional information
?
-
-
the enzyme is essentially involved in mitochondrial fatty acid beta-oxidation by catalyzing straight chain 3-hydroxyacyl-CoAs, the enzyme plays a role in Alzheimer's disease and Parkinson's disease, overview
-
-
?
additional information
?
-
-
the enzyme is involved in intracrinology and is essential for the metabolism of isoleucine and branched-chain fatty acids
-
-
?
additional information
?
-
-
the enzyme is involved in the penultimate step in mitochondrial fatty acid oxidation and in development of type 2 diabetes
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
activity of the enzyme it encodes is particularly high in the pancreas and especially in the islets of Langerhans
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high level expression in malignant prostatic epithelial cells
additional information
-
immunohistochemic analysis, more intense staining in islets than in the surrounding exocrine tissue, being strongly present in insulin-positive cells and only weakly in glucagon-positive alpha cells
high HADH expression level, activity of the enzyme it encodes is particularly high in the pancreas and especially in the islets of Langerhans
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
3-hydroxyacyl-CoA dehydrogenase catalyzes the third step in fatty acid beta-oxidation
additional information
malfunction
mutations in HADH cause hyperinsulinemic hypoglycemia that is precipitated by protein in a similar manner to the hyperinsulinism/hyperammonemia (HI/HA) syndrome, which is caused by mutations in the GLUD1 gene, encoding the enzyme glutamate dehydrogenase (GDH), suggesting a link between mitochondrial fatty acid oxidation, amino acid metabolism, and insulin secretion, clinical phenotypes, overview
malfunction
numerous human diseases are found related to mutations at HAD dimerization interface that is away from the catalytic pocket
additional information
molecular mechanism about the essential role of the HAD dimerization interface in its catalytic activity via allosteric effects, molecular dynamics simulation, overview
additional information
-
molecular mechanism about the essential role of the HAD dimerization interface in its catalytic activity via allosteric effects, molecular dynamics simulation, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). HCD2_HUMAN
261
0
26923
Swiss-Prot
other Location (Reliability: 5)
HCDH_HUMAN
314
0
34294
Swiss-Prot
Mitochondrion (Reliability: 2)
ECHP_HUMAN
723
0
79495
Swiss-Prot
Mitochondrion (Reliability: 5)
DHB4_HUMAN
736
0
79686
Swiss-Prot
Secretory Pathway (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
structure-function relationship of SCHAD, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
50 mM N(2-acetamido)-2-iminodiacetic acid, pH 6.5, polyethylene glycol 4000, 5 mM NAD+ hanging drop, crystals within 3 to 5 days at 18°C, enzyme structure is compromised of two domains, a NAD+-binding domain and a helical C-terminal domain
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D279E
-
naturally occuring polymorphism probably involved in development of type 2 diabetes
H152Q
-
naturally occuring polymorphism probably involved in development of type 2 diabetes
P86L
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naturally occuring polymorphism probably involved in development of type 2 diabetes
additional information
additional information
-
inactivation of the enzyme by siRNA expression, the mutants show reduced beta-oxidation of fatty acids
additional information
c.547-3_549delbis and IVS6-2a.gc are naturally occuring enzyme mutations causing human disease. Mapping of disease-relevant HAD mutations onto the crystal structure of human HAD, PDB ID 1F0Y
additional information
-
c.547-3_549delbis and IVS6-2a.gc are naturally occuring enzyme mutations causing human disease. Mapping of disease-relevant HAD mutations onto the crystal structure of human HAD, PDB ID 1F0Y
additional information
identified naturally occuring enzyme mutations are P258L, c.547-3_549del, c.547-3_549del, IVS6-2a>g, M188V, R236X, c.587delC, c.587delC, C.587delC, and c.261+IG>A from human hyperinsulinemic hypoglycemia patients, clinical data, overview
additional information
-
identified naturally occuring enzyme mutations are P258L, c.547-3_549del, c.547-3_549del, IVS6-2a>g, M188V, R236X, c.587delC, c.587delC, C.587delC, and c.261+IG>A from human hyperinsulinemic hypoglycemia patients, clinical data, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pharmacology
the short-chain 3-hydroxyacyl-CoA dehydrogenase is a target for intervention in case of Alzheimer's disease and Parkinson's disease
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Barycki, J.J.; O'Brian, L.K.; Bratt, J.M.; Zhang, R.; Sanishvili, R.; Strauss, A.W.; Banaszak, L.J.
Biochemical characterization and crystal structure determination of human heart short chain L-3-hydroxyacyl-CoA dehydrogenase provide insights into catalytic mechanism
Biochemistry
38
5786-5789
1999
Homo sapiens
He, X.Y.; Merz, G.; Mehta, P.; Schulz, H.; Yang, S.Y.
Human brain short chain L-3-hydroxyacyl Coenzyme A dehydrogenase is a singl-domain multifunctional enzyme
J. Biol. Chem.
274
15014-15019
1999
Homo sapiens
He, X.Y.; Schulz, H.; Yang, S.Y.
a human brain L-3-hydroxyacyl-coenzyme a dehydrogenase is identical to an amyloid beta-peptide-binding protein involved in Alzheimer's disease
J. Biol. Chem.
273
10741-10746
1998
Homo sapiens (Q99714), Homo sapiens
Vredendaal, P.J.C.M.; van den Berg, I.E.T.; Malingre, H.E.M.; Stroobants, A.K.; Olde Weghuis, D.E.M.; Berger, R.
Human short-chain L-3-hydroxyacyl-CoA dehydrogenase: cloning and characterization of the coding sequence
Biochem. Biophys. Res. Commun.
223
718-723
1996
Homo sapiens (Q16836), Homo sapiens
van Hove, E.C.; Hansen, T.; Dekker, J.M.; Reiling, E.; Nijpels, G.; Jorgensen, T.; Borch-Johnsen, K.; Hamid, Y.H.; Heine, R.J.; Pedersen, O.; Maassen, J.A.; t Hart, L.M.
The HADHSC gene encoding short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) and type 2 diabetes susceptibility: the DAMAGE study
Diabetes
55
3193-3196
2006
Homo sapiens
He, X.; Yang, S.
Roles of type 10 17beta-hydroxysteroid dehydrogenase in intracrinology and metabolism of isoleucine and fatty acids
Endocr. Metab. Immune Disord. Drug Targets
6
95-102
2006
Homo sapiens
Yang, S.Y.; He, X.Y.; Schulz, H.
3-Hydroxyacyl-CoA dehydrogenase and short chain 3-hydroxyacyl-CoA dehydrogenase in human health and disease
FEBS J.
272
4874-4883
2005
Sus scrofa, Homo sapiens (Q16836), Homo sapiens
Filling, C.; Keller, B.; Hirschberg, D.; Marschall, H.U.; Joernvall, H.; Bennett, M.J.; Oppermann, U.
Role of short-chain hydroxyacyl CoA dehydrogenases in SCHAD deficiency
Biochem. Biophys. Res. Commun.
368
6-11
2008
Homo sapiens
Martens, G.A.; Vervoort, A.; Van de Casteele, M.; Stange, G.; Hellemans, K.; Van Thi, H.V.; Schuit, F.; Pipeleers, D.
Specificity in beta cell expression of L-3-hydroxyacyl-CoA dehydrogenase, short chain, and potential role in down-regulating insulin release
J. Biol. Chem.
282
21134-21144
2007
Homo sapiens, Rattus norvegicus
Kapoor, R.R.; James, C.; Flanagan, S.E.; Ellard, S.; Eaton, S.; Hussain, K.
3-Hydroxyacyl-coenzyme A dehydrogenase deficiency and hyperinsulinemic hypoglycemia: characterization of a novel mutation and severe dietary protein sensitivity
J. Clin. Endocrinol. Metab.
94
2221-2225
2009
Homo sapiens
Heslegrave, A.; Hussain, K.
Novel insights into fatty acid oxidation, amino acid metabolism, and insulin secretion from studying patients with loss of function mutations in 3-hydroxyacyl-CoA dehydrogenase
J. Clin. Endocrinol. Metab.
98
496-501
2013
Homo sapiens (Q16836), Homo sapiens
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