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Information on EC 1.1.1.211 - long-chain-3-hydroxyacyl-CoA dehydrogenase
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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
-
beta-oxidation
- cardiomyopathy
- carnitine
- acylcarnitine
- citrate
- pregnancy
-
medium-chain
-
hadhb
- neuropathy
- hypoglycemia
- rhabdomyolysis
- alpha-subunits
- 3-ketoacyl-coa
- retinopathy
-
hellp
-
hypoketotic
- palmitoyltransferase
- vlcad
-
faods
-
3-hydroxyacyl-coenzyme
-
chorioretinopathy
- aciduria
-
pigmentary
-
very-long-chain
-
reye-like
- l-3-hydroxyacyl-coa
- degradation
- diagnostics
- medicine
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
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
2-enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase/3-oxoacyl-CoA thiolase
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3-hydroxyacyl-CoA dehydrogenase
beta-hydroxyacyl-CoA dehydrogenase
-
-
-
-
enoyl-coenzyme A (CoA) hydratase/3-hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase trifunctional protein
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LCHAD
long-chain 3-hydroxy acyl-CoA dehydrogenase
long-chain 3-hydroxy-acyl-CoA dehydrogenase
long-chain 3-hydroxyacyl coenzyme A dehydrogenase
long-chain 3-hydroxyacyl-CoA dehydrogenase
additional information
3-hydroxyacyl-CoA dehydrogenase
-
-
-
-
LCHAD
-
-
-
-
long-chain 3-hydroxyacyl coenzyme A dehydrogenase
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-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a long-chain (S)-3-hydroxyacyl-CoA + NAD+ = a long-chain 3-oxoacyl-CoA + NADH + H+
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-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
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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).
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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+
-
-
-
-
?
3-ketohexadecanoyl-CoA + NADH
3-hydroxyhexadecanoyl-CoA + NAD+
-
-
-
?
a long-chain (S)-3-hydroxyacyl-CoA + NAD+
a long-chain 3-oxoacyl-CoA + NADH + H+
-
-
-
-
?
a long-chain (S)-3-hydroxyacyl-CoA + NAD+
a long-chain 3-oxoacyl-CoA + NADH + H+
-
-
-
?
a long-chain (S)-3-hydroxyacyl-CoA + NAD+
a long-chain 3-oxoacyl-CoA + NADH + H+
-
-
-
?
a long-chain (S)-3-hydroxyacyl-CoA + NAD+
a long-chain 3-oxoacyl-CoA + NADH + H+
-
-
-
?
additional information
?
-
-
trifunctional, membrane bound, beta-oxidation enzyme
-
-
?
additional information
?
-
-
trifunctional, membrane bound, beta-oxidation enzyme
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-
?
additional information
?
-
-
LCHAD and mitochondrial trifunctional protein, EC 4.2.1.17, deficiency can lead to retinopathy and peripheral neuropathy
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-
?
additional information
?
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-
mutational LCHAD deficiency leads to accumulation of long-chain 3-hydroxyacylcarnitines and the severe chorioretinopathy, retinal phenotypes in enzyme deficient children, the progression of the disease can be prevented by a dietary therapy including supplementation with docosahexaenoic acid, DHA, overview
-
-
?
additional information
?
-
-
mutational enzyme deficiency may lead to acute fatty liver in pregnancy, a serious, often lethal hepatic disorder, overview
-
-
?
additional information
additional information
-
-
has also enoyl-CoA-hydratase activity
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-
?
additional information
additional information
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-
has also enoyl-CoA-hydratase activity
has also 3-ketoacyl-CoA thiolase activity
?
additional information
additional information
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-
has also enoyl-CoA-hydratase activity
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-
?
additional information
additional information
-
-
has also enoyl-CoA-hydratase activity
-
-
?
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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
a long-chain (S)-3-hydroxyacyl-CoA + NAD+
a long-chain 3-oxoacyl-CoA + NADH + H+
-
-
-
-
?
a long-chain (S)-3-hydroxyacyl-CoA + NAD+
a long-chain 3-oxoacyl-CoA + NADH + H+
-
-
-
?
a long-chain (S)-3-hydroxyacyl-CoA + NAD+
a long-chain 3-oxoacyl-CoA + NADH + H+
-
-
-
?
a long-chain (S)-3-hydroxyacyl-CoA + NAD+
a long-chain 3-oxoacyl-CoA + NADH + H+
-
-
-
?
additional information
?
-
-
trifunctional, membrane bound, beta-oxidation enzyme
-
-
?
additional information
?
-
-
trifunctional, membrane bound, beta-oxidation enzyme
-
-
?
additional information
?
-
-
LCHAD and mitochondrial trifunctional protein, EC 4.2.1.17, deficiency can lead to retinopathy and peripheral neuropathy
-
-
?
additional information
?
-
-
mutational LCHAD deficiency leads to accumulation of long-chain 3-hydroxyacylcarnitines and the severe chorioretinopathy, retinal phenotypes in enzyme deficient children, the progression of the disease can be prevented by a dietary therapy including supplementation with docosahexaenoic acid, DHA, overview
-
-
?
additional information
?
-
-
mutational enzyme deficiency may lead to acute fatty liver in pregnancy, a serious, often lethal hepatic disorder, overview
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
defatted serum albumin
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only with long-chain e.g. C16 3-ketoacyl-CoA, in concentrations higher than 0.6 mg/ml
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defatted serum albumin
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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
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only with long-chain e.g. C16 3-ketoacyl-CoA, in concentrations lower than 0.6 mg/ml
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defatted serum albumin
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only with long-chain e.g. C16 3-ketoacyl-CoA, in concentrations lower than 0.6 mg/ml
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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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-ketodecanoyl-CoA and 3-ketotetradecanoyl-CoA
additional information
-
it is specific for long chain substrate and has maximum activity with 3-ketohexadecanoyl-CoA
additional information
-
it is specific for long chain substrate and has maximum activity with 3-ketohexadecanoyl-CoA
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.2
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
retinal pigment epithelial monolayers are constructed by human induced pluripotent stem cell retina technology
brenda
additional information
-
long-chain fatty acid oxidation during fetal and early human development, overview
brenda
-
adult and fetal, strong expression in the myocard tissue, but not in vessels
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
malfunction
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the placenta of an 8-month-old child diagnosed with long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) deficiency shows maternal floor infarction/massive perivillous fibrin, MFI/MPVFD, phenotype, overview
malfunction
a patient with hemophagocytic lymphohistiocytosis and LCHAD deficiency suffers pancytopenia, liver failure, and rhabdomyolysis. LCHAD deficiency, especially in 1 to 6 months old infants with laboratory findings of hypoglycemia, metabolic acidosis, and elevated creatine kinase, may also have hemophagocytic lymphohistiocytosis (HLH), a secondary HLH may develop in patients with LCHAD deficiency
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
children with long-chain 3-hydroxyacyl-CoA dehydrogenasedeficiency (LCHAD) have a defect in the degradation of long-chain fatty acids and are at risk of hypoketotic hypoglycemia and insufficient energy production as well as accumulation of toxic fatty acid intermediates. lipolysis and accumulation of long chain acylcarnitines occurs before hypoglycemia in fasting children with LCHAD, which may indicate more limited fasting tolerance than previously suggested, phenotypes, overview. Early and increased lipolysis and accumulation of long chain acylcarnitines after 4 h of fasting, albeit no patients developed hypoglycemia
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-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and trifunctional protein (TFP) deficiency are accompanied by increased levels of 3-hydroxypalmitoleoyl-carnitine combined with other hydroxylated long chain acylcarnitines, analysis of acylcarnitine profile of two LCHADD patients, overview. Patients with propionic acidemia (PA) or methylmalonic acidemia (MMA) also show high levels of 3-hydroxypalmitoleoyl-carnitine and heptadecanoylcarnitine
malfunction
long-chain 3-hydroxyacyl-CoA dehydrogenase, LCHAD, deficiency is a defect of the TFP complex caused by a mutation in the HADHA gene on short arm of chromosome 2 (2p23). The most common mutation (1528G.C, G510Q) is responsible for at least one allele in 60100 percent of individuals with LCHAD deficiency. LCHAD and TFP deficiencies are caused by different genetic mutations in the same protein, mitochondrial trifunctional protein (MTFP). Long-chain fatty acids are broken down by the MTFP after initial metabolism by very long-chain acyl-CoA dehydrogenase. In individuals with LCHAD deficiency, there is one enzymatic defect (3-hydroxylacyl-CoA dehydrogenase) which results in accumulation of long-chain hydroxylacylcarnitines. In TFP deficiency, the process of the b-oxidation includes defects in three enzymes, enoyl-CoA hydratase, 3-hydroxyl-CoA dehydrogenase (LCHAD), and 3-ketothiolase, which results in accumulation of mixed, long-chain acylcarnitine species. Although disorders of trifunctional protein (TFP) complex including longchain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and mitochondrial TFP deficiencies are extremely rare, the combined incidence of mitochondrial fatty acid disorders is quite frequent. With the expansion of newborn screening, what were once considered uncommon disorders are being identified with increasing frequency in asymptomatic infants. Infants with inborn errors of metabolism can present with breathing difficulties, acidosis (or alkalosis), and hypoglycemia, phenotype, detailed overview
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
malfunction
the common homozygous mutation in the trifunctional protein alpha-subunit gene HADHA (hydroxyacyl-CoA dehydrogenase), c.1528G>C, affects the long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) activity of trifunctional protein and causes blindness in infancy. LCHAD deficiency patient retinal pigment epithelia have intense cytoplasmic neutral lipid accumulation, and lipidomic analysis reveals an increased triglyceride accumulation. Patient retinal pigment epithelia are small and irregular in shape, and their tight junctions are disorganized. Their ultratructure shows decreased pigmentation, few melanosomes, and more melanolysosomes. Early pathogenic changes in LCHADD retinopathy occur with robust lipid accumulation, inefficient pigmentation that is evident soon after differentiation, and a defect in forming tight junctions inducing apoptosis. LCHADD-retinal pigment epithelia are an important model for mitochondrial trifunctional protein (TFP) retinopathy
malfunction
defects in long-chain 3-hydroxy acyl-CoA dehydrogenase lead to hepatocellular carcinoma
malfunction
-
enzyme exon 15 deletion is embryonic lethal to the homozygous mice whereas heterozygous mice develop significant hepatic steatosis starting at young age (3 months old) and hepatocellular carcinoma at older age (more than13 months old) without any evidence of fibrosis or cirrhosis
malfunction
-
long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is characterized by lethargy, hypoglycemia, hypotonia, cardiomyopathy, and acute metabolic crisis
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
-
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
-
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
-
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)
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)
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)
-
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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_HUMAN
763
0
83000
Swiss-Prot
Mitochondrion (Reliability: 1)
ECHA_MOUSE
763
0
82670
Swiss-Prot
Mitochondrion (Reliability: 1)
ECHA_PIG
763
0
83107
Swiss-Prot
Mitochondrion (Reliability: 1)
ECHA_RAT
763
0
82665
Swiss-Prot
Mitochondrion (Reliability: 1)
A0A0N1FXG9_9ACTN
600
0
63188
TrEMBL
-
A0A2I0AFV3_9ASPA
667
1
72983
TrEMBL
Secretory Pathway