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Information on EC 1.1.1.211 - long-chain-3-hydroxyacyl-CoA dehydrogenase and Organism(s) Rattus norvegicus and UniProt Accession Q64428
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1.1.1.211 long-chain-3-hydroxyacyl-CoA dehydrogenaseIUBMB Comments
This enzyme was purified from the mitochondrial inner membrane. The enzyme has a preference for long-chain substrates, and activity with a C16 substrate was 6- to 15-fold higher than with a C4 substrate (cf. EC 1.1.1.35 3-hydroxyacyl-CoA dehydrogenase).
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Word Map
- 1.1.1.211
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beta-oxidation
- cardiomyopathy
- carnitine
- acylcarnitine
- citrate
- pregnancy
-
medium-chain
-
hadhb
- neuropathy
- hypoglycemia
- rhabdomyolysis
- alpha-subunits
- 3-ketoacyl-coa
- retinopathy
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hellp
-
hypoketotic
- palmitoyltransferase
- vlcad
-
faods
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3-hydroxyacyl-coenzyme
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chorioretinopathy
- aciduria
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pigmentary
-
very-long-chain
-
reye-like
- l-3-hydroxyacyl-coa
- degradation
- diagnostics
- medicine
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Reaction Schemes
Synonyms
lchad, hadha, long-chain 3-hydroxyacyl-coa dehydrogenase, mitochondrial trifunctional protein, beta-hydroxyacyl-coa dehydrogenase, long chain 3-hydroxyacyl-coa dehydrogenase, long-chain 3-hydroxyacyl coenzyme a dehydrogenase, long-chain 3-hydroxy acyl-coa dehydrogenase, long-chain 3-hydroxy-acyl-coa dehydrogenase, long-chain-3-hydroxyacyl-coa dehydrogenase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
enoyl-coenzyme A (CoA) hydratase/3-hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase trifunctional protein
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3-hydroxyacyl-CoA dehydrogenase
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-
-
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beta-hydroxyacyl-CoA dehydrogenase
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-
-
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LCHAD
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-
-
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long-chain 3-hydroxyacyl coenzyme A dehydrogenase
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-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
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-
-
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oxidation
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-
-
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reduction
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-
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SYSTEMATIC NAME
IUBMB Comments
long-chain-(S)-3-hydroxyacyl-CoA:NAD+ oxidoreductase
This enzyme was purified from the mitochondrial inner membrane. The enzyme has a preference for long-chain substrates, and activity with a C16 substrate was 6- to 15-fold higher than with a C4 substrate (cf. EC 1.1.1.35 3-hydroxyacyl-CoA dehydrogenase).
CAS REGISTRY NUMBER
COMMENTARY
84177-52-6
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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
3-ketohexadecanoyl-CoA + NADH
3-hydroxyhexadecanoyl-CoA + NAD+
-
-
-
?
a long-chain (S)-3-hydroxyacyl-CoA + NAD+
a long-chain 3-oxoacyl-CoA + NADH + H+
-
-
-
?
additional information
additional information
-
-
has also enoyl-CoA-hydratase activity
-
-
?
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
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
defatted serum albumin
-
only with long-chain e.g. C16 3-ketoacyl-CoA, in concentrations higher than 0.6 mg/ml
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
defatted serum albumin
-
only with long-chain e.g. C16 3-ketoacyl-CoA, in concentrations lower than 0.6 mg/ml
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
it is specific for long chain substrate and has maximum activity with 3-ketohexadecanoyl-CoA
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
the mitochondrial trifunctional protein (MTP) is an enzymatic complex associated with the inner mitochondrial membrane and participates in the beta-oxidation of long-chain fatty acids. MTP comprises the activities of 3-hydroxyacyl-CoA dehydrogenase (LCHAD), 2-enoyl-CoA hydratase and 3-oxoacyl-CoA thiolase (LKAT)
physiological function
long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) is part of the mitochondrial trifunctional protein (MTP) complex that also comprises other two enzyme activities, long-chain enoyl-CoA hydratase and long-chain ketoacyl-CoA thiolase (LCKT). This complex is responsible for mitochondrial oxidation of long-chain fatty acids (LCFA)
malfunction
analysis of the effects of the major long-chain monocarboxylic 3-hydroxylated fatty acids (LCHFA) accumulating in the disorders mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) deficiencies, namely 3-hydroxytetradecanoic (3HTA) and 3-hydroxypalmitic (3HPA) acids, on important mitochondrial functions in rat skeletal muscle mitochondria 3HTA and 3HPA markedly increases resting and decrease ADP-stimulated and CCCP-stimulated (uncoupled) respiration. 3HPA provokes similar effects in permeabilized skeletal muscle fibers, validating the results obtained in purified mitochondria. 3HTA and 3HPA markedly diminish mitochondrial membrane potential, NAD(P)H content, and Ca2+ retention capacity in Ca2+-loaded mitochondria. Mitochondrial permeability transition (mPT) induction probably underlies these effects since they are totally prevented by cyclosporin A and ADP. In contrast, the dicarboxylic analogue of 3HTA does not alter the tested parameters. 3HTA and 3HPA behave as metabolic inhibitors, uncouplers of oxidative phosphorylation and mPT inducers in skeletal muscle. The pathomechanisms disrupting mitochondrial homeostasis may be involved in the muscle alterations characteristic ofMTP and LCHAD deficiencies
malfunction
effects of long-chain 3-hydroxylated fatty acids (LCHFA) that accumulate in LCHAD deficiency on liver bioenergetics in mitochondrial preparations from young rats: 3-hydroxytetradecanoic (3HTA) and 3-hydroxypalmitic (3HPA) acids, the monocarboxylic acids that are found at the highest tissue concentrations in this disorder, act as metabolic inhibitors and uncouplers of oxidative phosphorylation. These fatty acids decrease ADP-stimulated and uncoupled respiration, mitochondrial membrane potential and NAD(P)H content, and, in contrast, increased resting respiration. 3HTA and 3HPA markedly reduce Ca2+ retention capacity and induce swelling in C2+-loaded mitochondria. The effects are mediated by mitochondrial permeability transition (MPT) induction since they are totally prevented by the classical MPT inhibitors cyclosporin A and ADP, as well as by ruthenium red, a Ca2+ uptake blocker. Long-chain monocarboxylic 3-hydroxylated fatty acids alter oxygen consumption in liver mitochondria. The major monocarboxylic LCHFA accumulating in LCHAD deficiency disrupt energy mitochondrial homeostasis in the liver leading to liver dysfunction
malfunction
long-chain 3-hydroxy fatty acids accumulating in long-chain 3-hydroxyacyl-CoA dehydrogenase and mitochondrial trifunctional protein deficiencies uncouple oxidative phosphorylation in heart mitochondria. Cardiomyopathy is a common clinical feature of some inherited disorders of mitochondrial fatty acid beta-oxidation including mitochondrial trifunctional protein (MTP) and isolated long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies. 3-Hydroxytetradecanoic (3HTA) and 3-hydroxypalmitic (3HPA) acids increase resting respiration and diminish the respiratory control and ADP/O ratios using glutamate/malate or succinate as substrates. 3-hydroxydodecanoic (3HDDA), 3HTA and 3HPA decrease DELTAPsi, the matrix NAD(P)H pool, and hydrogen peroxide production. These fatty acids behave as uncouplers of oxidative phosphorylation. 3HTA-induced uncoupling-effect is not mediated by the adenine nucleotide translocator and that this fatty acid induced the mitochondrial permeability transition pore opening in calcium-loaded organelles since cyclosporin A prevents the reduction of mitochondrial DELTAPsi and swelling provoked by 3HTA
malfunction
Long-chain 3-hydroxylated fatty acids (LCHFA) accumulate in long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiencies. 3-Hydroxytetradecanoic acid (3 HTA) reduces mitochondrial membrane potential, NAD(P)H levels, Ca2+ retention capacity and ATP content, besides inducing swelling, cytochrome c release and H2O2 production in Ca2+-loaded mitochondrial preparations. Cyclosporine A plus ADP, as well as ruthenium red, a Ca2+ uptake blocker, prevent these effects, suggesting the involvement of the mitochondrial permeability transition pore (mPTP) and an important role for Ca2+, respectively. 3-Hydroxydodecanoic and 3-hydroxypalmitic acids, that also accumulate in LCHAD and MTP deficiencies, similarly induce mitochondrial swelling and decrease ATP content, but to a variable degree pending on the size of their carbon chain. Pathological neurological phenotype, detailed overview
malfunction
mitochondrial trifunctional protein and long-chain 3-hydroxyacyl-CoA dehydrogenase deficiencies are fatty acid oxidation disorders biochemically characterized by tissue accumulation of long-chain fatty acids and derivatives, including the monocarboxylic long-chain 3-hydroxy fatty acids (LCHFAs) 3-hydroxytetradecanoic acid (3HTA) and 3-hydroxypalmitic acid (3HPA). Deregulation of mitochondrial functions can be provoked by long-chain fatty acid accumulating in long-chain 3-hydroxyacyl-CoA dehydrogenase and mitochondrial permeability transition deficiencies in rat heart. 3HTA and 3HPA significantly decrease mitochondrial membrane potential, the matrix NAD(P)H pool and Ca2+ retention capacity, and also induced mitochondrial swelling. These fatty acids also provoke a marked decrease of ATP production reflecting severe energy dysfunction. 3HTA-induced mitochondrial alterations are completely prevented by the classical mitochondrial permeability transition (mPT) inhibitors cyclosporin A and ADP, as well as by ruthenium red, a Ca2+ uptake blocker, indicating that LCHFAs induce Ca2+-dependent mPT pore opening. Comparison of the susceptibility of heart and brain to the toxic effects of these hydroxylated fatty acids, phenotypes, 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). ECHA_RAT
763
0
82665
Swiss-Prot
Mitochondrion (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
nickel strongly represses mitochondrial fatty acid oxidation, the pathway by which fatty acids are catabolized for energy, in both primary human lung fibroblasts and mouse embryonic fibroblasts
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
El-Fakhri, M.; Middleton, B.
The existence of an inner-membrane-bound, long acyl-chain-specific 3-hydroxyacyl-CoA dehydrogenase in mammalian mitochondria
Biochim. Biophys. Acta
713
270-279
1982
Oryctolagus cuniculus, Rattus norvegicus
Uchida, Y.; Izai, K.; Orii, T.; Hashimoto, T.
Novel fatty acid beta-oxidation enzymes in rat liver mitochondria. II. Purification and properties of enoyl-coenzyme A (CoA) hydratase/3-hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase trifunctional protein
J. Biol. Chem.
267
1034-1041
1992
Rattus norvegicus (Q64428)
Tonin, A.M.; Amaral, A.U.; Busanello, E.N.; Gasparotto, J.; Gelain, D.P.; Gregersen, N.; Wajner, M.
Mitochondrial bioenergetics deregulation caused by long-chain 3-hydroxy fatty acids accumulating in LCHAD and MTP deficiencies in rat brain: a possible role of mPTP opening as a pathomechanism in these disorders?
Biochim. Biophys. Acta
1842
1658-1667
2014
Rattus norvegicus (Q64428), Rattus norvegicus Wistar (Q64428)
Hickmann, F.H.; Cecatto, C.; Kleemann, D.; Monteiro, W.O.; Castilho, R.F.; Amaral, A.U.; Wajner, M.
Uncoupling, metabolic inhibition and induction of mitochondrial permeability transition in rat liver mitochondria caused by the major long-chain hydroxyl monocarboxylic fatty acids accumulating in LCHAD deficiency
Biochim. Biophys. Acta
1847
620-628
2015
Rattus norvegicus (Q64428), Rattus norvegicus Wistar (Q64428)
Cecatto, C.; Hickmann, F.H.; Rodrigues, M.D.; Amaral, A.U.; Wajner, M.
Deregulation of mitochondrial functions provoked by long-chain fatty acid accumulating in long-chain 3-hydroxyacyl-CoA dehydrogenase and mitochondrial permeability transition deficiencies in rat heart - mitochondrial permeability transition pore opening as a potential contributing pathomechanism of cardiac alterations in these disorders
FEBS J.
282
4714-4726
2015
Rattus norvegicus (Q64428)
Tonin, A.; Amaral, A.; Busanello, E.; Grings, M.; Castilho, R.; Wajner, M.
Long-chain 3-hydroxy fatty acids accumulating in long-chain 3-hydroxyacyl-CoA dehydrogenase and mitochondrial trifunctional protein deficiencies uncouple oxidative phosphorylation in heart mitochondria
J. Bioenerg. Biomembr.
45
47-57
2013
Rattus norvegicus (Q64428), Rattus norvegicus Wistar (Q64428)
Cecatto, C.; Godoy, K.d.o.s..S.; da Silva, J.C.; Amaral, A.U.; Wajner, M.
Disturbance of mitochondrial functions provoked by the major long-chain 3-hydroxylated fatty acids accumulating in MTP and LCHAD deficiencies in skeletal muscle
Toxicol. In Vitro
36
1-9
2016
Rattus norvegicus (Q64428), Rattus norvegicus Wistar (Q64428)
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