C22H35N7O17P3RS
C22H35N7O17P3SR
|
CC(C)(COP(O)(=O)OP(O)(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP(O)(O)=O)n1cnc2c(N)ncnc12)[C@@H](O)C(=O)NCCC(=O)NCCSC([*])=O |
|
Mus musculus
(NCBI:txid10090)
|
Source: BioModels - MODEL1507180067
See:
PubMed
|
acyl donor
Any donor that can transfer acyl groups between molecular entities.
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|
View more via ChEBI Ontology
Outgoing
|
acyl-CoA
(CHEBI:17984)
has functional parent
coenzyme A
(CHEBI:15346)
acyl-CoA
(CHEBI:17984)
has role
acyl donor
(CHEBI:62049)
acyl-CoA
(CHEBI:17984)
is a
6-aminopurines
(CHEBI:20706)
acyl-CoA
(CHEBI:17984)
is a
nucleotide derivative
(CHEBI:231540)
acyl-CoA
(CHEBI:17984)
is a
secondary carboxamide
(CHEBI:140325)
acyl-CoA
(CHEBI:17984)
is a
thioester
(CHEBI:51277)
acyl-CoA
(CHEBI:17984)
is conjugate acid of
acyl-CoA(4−)
(CHEBI:58342)
|
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Incoming
|
β-alanyl-CoA
(CHEBI:15507)
is a
acyl-CoA
(CHEBI:17984)
γ-butyrobetainyl-CoA
(CHEBI:61517)
is a
acyl-CoA
(CHEBI:17984)
ω-carboxyacyl-CoA
(CHEBI:37555)
is a
acyl-CoA
(CHEBI:17984)
(2,3,3-trimethyl-5-oxocyclopent-3-enyl)acetyl-CoA
(CHEBI:27866)
is a
acyl-CoA
(CHEBI:17984)
(2E)-hexadecenedioyl-CoA
(CHEBI:77183)
is a
acyl-CoA
(CHEBI:17984)
(2E)-tetradecenedioyl-CoA
(CHEBI:77170)
is a
acyl-CoA
(CHEBI:17984)
(2S)-methylsuccinyl-CoA
(CHEBI:81672)
is a
acyl-CoA
(CHEBI:17984)
(2Z)-4-carboxy-2-sulfanylbut-2-enoyl-CoA
(CHEBI:71243)
is a
acyl-CoA
(CHEBI:17984)
(3R)-3-amino-3-phenylpropanoyl-CoA
(CHEBI:83170)
is a
acyl-CoA
(CHEBI:17984)
(4-coumaroyl)acetyl-CoA
(CHEBI:71215)
is a
acyl-CoA
(CHEBI:17984)
(E)-2-benzylidenesuccinyl-CoA
(CHEBI:27639)
is a
acyl-CoA
(CHEBI:17984)
(E)-4-(trimethylammonio)but-2-enoyl-CoA
(CHEBI:61123)
is a
acyl-CoA
(CHEBI:17984)
(R)-phenyllactoyl-CoA
(CHEBI:11010)
is a
acyl-CoA
(CHEBI:17984)
(S)-2-benzoylsuccinyl-CoA
(CHEBI:28882)
is a
acyl-CoA
(CHEBI:17984)
1,4-dihydroxy-2-naphthoyl-CoA
(CHEBI:52668)
is a
acyl-CoA
(CHEBI:17984)
2,3-epoxy-2,3-dihydrobenzoyl-CoA
(CHEBI:90162)
is a
acyl-CoA
(CHEBI:17984)
2,5-dihydroxybenzoyl-CoA
(CHEBI:90176)
is a
acyl-CoA
(CHEBI:17984)
2-(1,2-epoxy-1,2-dihydrophenyl)acetyl-CoA
(CHEBI:63547)
is a
acyl-CoA
(CHEBI:17984)
2-amino-5-oxocyclohex-1-enecarbonyl-CoA
(CHEBI:18206)
is a
acyl-CoA
(CHEBI:17984)
2-aminobenzoylacetyl-CoA
(CHEBI:131952)
is a
acyl-CoA
(CHEBI:17984)
2-carboxyacyl-CoA
(CHEBI:84127)
is a
acyl-CoA
(CHEBI:17984)
2-furoyl-CoA
(CHEBI:15474)
is a
acyl-CoA
(CHEBI:17984)
2-hydroxy-7-methoxy-5-methyl-1-naphthoyl-CoA
(CHEBI:79293)
is a
acyl-CoA
(CHEBI:17984)
2-naphthoyl-CoA
(CHEBI:34300)
is a
acyl-CoA
(CHEBI:17984)
2-oxepin-2(3H)-ylideneacetyl-CoA
(CHEBI:63251)
is a
acyl-CoA
(CHEBI:17984)
2-oxoglutaryl-CoA
(CHEBI:71364)
is a
acyl-CoA
(CHEBI:17984)
3,5-dihydroxyphenylacetyl-CoA
(CHEBI:31103)
is a
acyl-CoA
(CHEBI:17984)
3,8-dioxooct-5-enoyl-CoA
(CHEBI:63256)
is a
acyl-CoA
(CHEBI:17984)
3-(4-hydroxy-3-methoxyphenyl)-3-oxopropanoyl-CoA
(CHEBI:142889)
is a
acyl-CoA
(CHEBI:17984)
3-(m-hydroxyphenyl)propanoyl-CoA
(CHEBI:87996)
is a
acyl-CoA
(CHEBI:17984)
3-(methylthio)acryloyl-CoA
(CHEBI:85528)
is a
acyl-CoA
(CHEBI:17984)
3-(methylthio)propanoyl-CoA
(CHEBI:83579)
is a
acyl-CoA
(CHEBI:17984)
3-[(3aS,4S,5R,7aS)-5-hydroxy-7a-methyl-1-oxo-octahydroinden-4-yl]propanoyl-CoA
(CHEBI:84601)
is a
acyl-CoA
(CHEBI:17984)
3-[({2-[(3-{[4-({[({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)oxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)-1,2-dihydroxy-3,3-dimethylbutylidene]amino}-1-hydroxypropylidene)amino]ethyl}sulfanyl)carbonyl]-4-hydroxy-4-phenylbutanoic acid
(CHEBI:184474)
is a
acyl-CoA
(CHEBI:17984)
3-dehydrocarnityl CoA
(CHEBI:85886)
is a
acyl-CoA
(CHEBI:17984)
3-hydroxy-3-(methylthio)propanoyl-CoA
(CHEBI:85529)
is a
acyl-CoA
(CHEBI:17984)
3-isopropenylpimeloyl-CoA
(CHEBI:37439)
is a
acyl-CoA
(CHEBI:17984)
3-oxo-5,6-dehydrosuberyl-CoA
(CHEBI:63253)
is a
acyl-CoA
(CHEBI:17984)
3-oxo-8-carboxy-5-octenoyl-CoA
(CHEBI:186430)
is a
acyl-CoA
(CHEBI:17984)
3-oxodecanedioyl-CoA
(CHEBI:76445)
is a
acyl-CoA
(CHEBI:17984)
3-oxododecanedioyl-CoA
(CHEBI:76439)
is a
acyl-CoA
(CHEBI:17984)
3-oxohexadecanedioyl-CoA
(CHEBI:77191)
is a
acyl-CoA
(CHEBI:17984)
3-oxooctanedioyl-CoA
(CHEBI:76426)
is a
acyl-CoA
(CHEBI:17984)
3-Oxopimelyl-CoA
(CHEBI:172855)
is a
acyl-CoA
(CHEBI:17984)
3-oxotetradecanedioyl-CoA
(CHEBI:77172)
is a
acyl-CoA
(CHEBI:17984)
3-phenylpropanoyl-CoA
(CHEBI:85675)
is a
acyl-CoA
(CHEBI:17984)
3-substituted propionyl-CoA
(CHEBI:65122)
is a
acyl-CoA
(CHEBI:17984)
3-sulfinopropionyl-CoA
(CHEBI:79221)
is a
acyl-CoA
(CHEBI:17984)
4-(2-carboxyphenyl)-4-oxobutanoyl-CoA
(CHEBI:15509)
is a
acyl-CoA
(CHEBI:17984)
4-({[({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)oxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)-2-hydroxy-N-{2-[(2-{[2-(4-hydroxyphenyl)acetyl]sulfanyl}ethyl)-C-hydroxycarbonimidoyl]ethyl}-3,3-dimethylbutanimidic acid
(CHEBI:185055)
is a
acyl-CoA
(CHEBI:17984)
4-acetamidobutanoyl-CoA
(CHEBI:28684)
is a
acyl-CoA
(CHEBI:17984)
4-carboxy-2-thioxobutanoyl-CoA
(CHEBI:71313)
is a
acyl-CoA
(CHEBI:17984)
4-isopropenyl-2-oxocyclohexane-1-carbonyl-CoA
(CHEBI:29489)
is a
acyl-CoA
(CHEBI:17984)
5-hydroxy-2-furoyl-CoA
(CHEBI:15510)
is a
acyl-CoA
(CHEBI:17984)
5-hydroxyferuloyl-CoA
(CHEBI:31136)
is a
acyl-CoA
(CHEBI:17984)
5-hydroxythiophene-2-carbonyl-CoA
(CHEBI:15502)
is a
acyl-CoA
(CHEBI:17984)
5-oxo-furan-2-acetyl-CoA
(CHEBI:49304)
is a
acyl-CoA
(CHEBI:17984)
9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oyl-CoA
(CHEBI:79246)
is a
acyl-CoA
(CHEBI:17984)
N,N,N-trimethylglycyl-CoA
(CHEBI:85888)
is a
acyl-CoA
(CHEBI:17984)
trans-2,3-didehydroadipoyl-CoA
(CHEBI:49295)
is a
acyl-CoA
(CHEBI:17984)
trans-2-decenedioyl-CoA
(CHEBI:76443)
is a
acyl-CoA
(CHEBI:17984)
trans-2-dodecenedioyl-CoA
(CHEBI:76427)
is a
acyl-CoA
(CHEBI:17984)
trans-2-octenedioyl-CoA
(CHEBI:76423)
is a
acyl-CoA
(CHEBI:17984)
L-cysteine coenzyme A disulfide
(CHEBI:21263)
is a
acyl-CoA
(CHEBI:17984)
L-firefly luciferyl-CoA
(CHEBI:139035)
is a
acyl-CoA
(CHEBI:17984)
[(1R)-2,2,3-trimethyl-5-oxocyclopent-3-enyl]acetyl-CoA
(CHEBI:64900)
is a
acyl-CoA
(CHEBI:17984)
[(2R)-3,3,4-trimethyl-6-oxo-3,6-dihydro-1H-pyran-2-yl]acetyl-CoA
(CHEBI:64819)
is a
acyl-CoA
(CHEBI:17984)
Acetyl coenzyme A (Acetyl-CoA)
(CHEBI:180918)
is a
acyl-CoA
(CHEBI:17984)
acetyl-CoA
(CHEBI:15351)
is a
acyl-CoA
(CHEBI:17984)
aroyl-CoA
(CHEBI:61940)
is a
acyl-CoA
(CHEBI:17984)
ascr#1-CoA
(CHEBI:139645)
is a
acyl-CoA
(CHEBI:17984)
ascr#10-CoA
(CHEBI:139616)
is a
acyl-CoA
(CHEBI:17984)
ascr#21-CoA
(CHEBI:139651)
is a
acyl-CoA
(CHEBI:17984)
ascr#22-CoA
(CHEBI:139654)
is a
acyl-CoA
(CHEBI:17984)
ascr#3-CoA
(CHEBI:139705)
is a
acyl-CoA
(CHEBI:17984)
ascr#7-CoA
(CHEBI:139711)
is a
acyl-CoA
(CHEBI:17984)
benzoylacetyl-CoA
(CHEBI:27388)
is a
acyl-CoA
(CHEBI:17984)
biotinyl-CoA
(CHEBI:15516)
is a
acyl-CoA
(CHEBI:17984)
bkos#9-CoA
(CHEBI:139962)
is a
acyl-CoA
(CHEBI:17984)
caffeoyl-CoA
(CHEBI:15518)
is a
acyl-CoA
(CHEBI:17984)
cinnamoyl-CoA
(CHEBI:15463)
is a
acyl-CoA
(CHEBI:17984)
cinnamoyl-CoAs
(CHEBI:23253)
is a
acyl-CoA
(CHEBI:17984)
CoA(12:0(3Ke))
(CHEBI:165616)
is a
acyl-CoA
(CHEBI:17984)
cyclohex-1-ene-1-carbonyl-CoA
(CHEBI:28005)
is a
acyl-CoA
(CHEBI:17984)
cyclohexa-1,4-diene-1-carbonyl-CoA
(CHEBI:28443)
is a
acyl-CoA
(CHEBI:17984)
cyclohexa-2,5-diene-1-carbonyl-CoA
(CHEBI:27610)
is a
acyl-CoA
(CHEBI:17984)
cyclohexane-1-carbonyl-CoA
(CHEBI:28557)
is a
acyl-CoA
(CHEBI:17984)
dihydrocaffeoyl-CoA
(CHEBI:87451)
is a
acyl-CoA
(CHEBI:17984)
fatty acyl-CoA
(CHEBI:37554)
is a
acyl-CoA
(CHEBI:17984)
feruloyl-CoA
(CHEBI:14261)
is a
acyl-CoA
(CHEBI:17984)
feruloylacetyl-CoA
(CHEBI:71236)
is a
acyl-CoA
(CHEBI:17984)
formyl-CoA
(CHEBI:15522)
is a
acyl-CoA
(CHEBI:17984)
haloacyl-CoA
(CHEBI:62048)
is a
acyl-CoA
(CHEBI:17984)
hexadecanedioyl-CoA
(CHEBI:77208)
is a
acyl-CoA
(CHEBI:17984)
hydroxyacyl-CoA
(CHEBI:62618)
is a
acyl-CoA
(CHEBI:17984)
indol-3-ylacetyl-CoA
(CHEBI:12755)
is a
acyl-CoA
(CHEBI:17984)
malonamoyl-CoA
(CHEBI:28334)
is a
acyl-CoA
(CHEBI:17984)
malonyl-CoA methyl ester
(CHEBI:71244)
is a
acyl-CoA
(CHEBI:17984)
Malonyl-CoA semialdehyde
(CHEBI:177266)
is a
acyl-CoA
(CHEBI:17984)
malonyl-CoAs
(CHEBI:25136)
is a
acyl-CoA
(CHEBI:17984)
methacrylyl-CoA
(CHEBI:27754)
is a
acyl-CoA
(CHEBI:17984)
mevalonyl-CoA
(CHEBI:133868)
is a
acyl-CoA
(CHEBI:17984)
oscr#1-CoA
(CHEBI:139993)
is a
acyl-CoA
(CHEBI:17984)
oscr#10-CoA
(CHEBI:139966)
is a
acyl-CoA
(CHEBI:17984)
oscr#12-CoA
(CHEBI:139969)
is a
acyl-CoA
(CHEBI:17984)
oscr#13-CoA
(CHEBI:139973)
is a
acyl-CoA
(CHEBI:17984)
oscr#14-CoA
(CHEBI:139976)
is a
acyl-CoA
(CHEBI:17984)
oscr#15-CoA
(CHEBI:139979)
is a
acyl-CoA
(CHEBI:17984)
oscr#16-CoA
(CHEBI:139982)
is a
acyl-CoA
(CHEBI:17984)
oscr#17-CoA
(CHEBI:139985)
is a
acyl-CoA
(CHEBI:17984)
oscr#18-CoA
(CHEBI:139988)
is a
acyl-CoA
(CHEBI:17984)
oscr#19-CoA
(CHEBI:139991)
is a
acyl-CoA
(CHEBI:17984)
oscr#20-CoA
(CHEBI:139996)
is a
acyl-CoA
(CHEBI:17984)
oscr#21-CoA
(CHEBI:139999)
is a
acyl-CoA
(CHEBI:17984)
oscr#22-CoA
(CHEBI:140002)
is a
acyl-CoA
(CHEBI:17984)
oscr#23-CoA
(CHEBI:140005)
is a
acyl-CoA
(CHEBI:17984)
oscr#24-CoA
(CHEBI:140008)
is a
acyl-CoA
(CHEBI:17984)
oscr#25-CoA
(CHEBI:140011)
is a
acyl-CoA
(CHEBI:17984)
oscr#26-CoA
(CHEBI:140014)
is a
acyl-CoA
(CHEBI:17984)
oscr#27-CoA
(CHEBI:140017)
is a
acyl-CoA
(CHEBI:17984)
oscr#28-CoA
(CHEBI:140020)
is a
acyl-CoA
(CHEBI:17984)
oscr#29-CoA
(CHEBI:140023)
is a
acyl-CoA
(CHEBI:17984)
oscr#3-CoA
(CHEBI:140053)
is a
acyl-CoA
(CHEBI:17984)
oscr#30-CoA
(CHEBI:140027)
is a
acyl-CoA
(CHEBI:17984)
oscr#31-CoA
(CHEBI:140030)
is a
acyl-CoA
(CHEBI:17984)
oscr#32-CoA
(CHEBI:140033)
is a
acyl-CoA
(CHEBI:17984)
oscr#33-CoA
(CHEBI:140036)
is a
acyl-CoA
(CHEBI:17984)
oscr#34-CoA
(CHEBI:140039)
is a
acyl-CoA
(CHEBI:17984)
oscr#35-CoA
(CHEBI:140042)
is a
acyl-CoA
(CHEBI:17984)
oscr#36-CoA
(CHEBI:140045)
is a
acyl-CoA
(CHEBI:17984)
oscr#37-CoA
(CHEBI:140048)
is a
acyl-CoA
(CHEBI:17984)
oscr#38-CoA
(CHEBI:140051)
is a
acyl-CoA
(CHEBI:17984)
oscr#7-CoA
(CHEBI:140056)
is a
acyl-CoA
(CHEBI:17984)
oscr#9-CoA
(CHEBI:140059)
is a
acyl-CoA
(CHEBI:17984)
perillyl-coenzyme A
(CHEBI:37002)
is a
acyl-CoA
(CHEBI:17984)
phenoxyacetyl-CoA
(CHEBI:28964)
is a
acyl-CoA
(CHEBI:17984)
phenylacetyl-CoA
(CHEBI:15537)
is a
acyl-CoA
(CHEBI:17984)
phenylacetyl-CoAs
(CHEBI:25981)
is a
acyl-CoA
(CHEBI:17984)
phenylglyoxylyl-CoA
(CHEBI:50117)
is a
acyl-CoA
(CHEBI:17984)
phytanoyl-CoAs
(CHEBI:26114)
is a
acyl-CoA
(CHEBI:17984)
pimeloyl-CoAs
(CHEBI:26132)
is a
acyl-CoA
(CHEBI:17984)
propenoyl-CoA
(CHEBI:26302)
is a
acyl-CoA
(CHEBI:17984)
propionyl-CoA
(CHEBI:15539)
is a
acyl-CoA
(CHEBI:17984)
Salicyl-CoA
(CHEBI:165618)
is a
acyl-CoA
(CHEBI:17984)
steroidal acyl-CoA
(CHEBI:52135)
is a
acyl-CoA
(CHEBI:17984)
sulfoacetyl-CoA
(CHEBI:61992)
is a
acyl-CoA
(CHEBI:17984)
tetradecanedioyl-CoA
(CHEBI:77207)
is a
acyl-CoA
(CHEBI:17984)
thiophene-2-carbonyl-CoA
(CHEBI:15542)
is a
acyl-CoA
(CHEBI:17984)
tinapoyl-CoA
(CHEBI:27009)
is a
acyl-CoA
(CHEBI:17984)
acyl-CoA(4−)
(CHEBI:58342)
is conjugate base of
acyl-CoA
(CHEBI:17984)
|
Acyl coenzyme A
|
KEGG COMPOUND
|
Acyl-CoA
|
KEGG COMPOUND
|
Hostetler HA, Lupas D, Tan Y, Dai J, Kelzer MS, Martin GG, Woldegiorgis G, Kier AB, Schroeder F (2011) Acyl-CoA binding proteins interact with the acyl-CoA binding domain of mitochondrial carnitine palmitoyl transferase I. Molecular and cellular biochemistry 355, 135-148 [PubMed:21541677] [show Abstract] Although the rate limiting step in mitochondrial fatty acid oxidation, catalyzed by carnitine palmitoyl transferase I (CPTI), utilizes long-chain fatty acyl-CoAs (LCFA-CoA) as a substrate, how LCFA-CoA is transferred to CPTI remains elusive. Based on secondary structural predictions and conserved tryptophan residues, the cytoplasmic C-terminal domain was hypothesized to be the LCFA-CoA binding site and important for interaction with cytoplasmic LCFA-CoA binding/transport proteins to provide a potential route for LCFA-CoA transfer. To begin to address this question, the cytoplasmic C-terminal region of liver CPTI (L-CPTI) was recombinantly expressed and purified. Data herein showed for the first time that the L-CPTI C-terminal 89 residues were sufficient for high affinity binding of LCFA-CoA (K (d) = 2-10 nM) and direct interaction with several cytoplasmic LCFA-CoA binding proteins (K (d) < 10 nM), leading to enhanced CPTI activity. Furthermore, alanine substitutions for tryptophan in L-CPTI (W391A and W452A) altered secondary structure, decreased binding affinity for LCFA-CoA, and almost completely abolished L-CPTI activity, suggesting that these amino acids may be important for ligand stabilization necessary for L-CPTI activity. Moreover, while decreased activity of the W452A mutant could be explained by decreased binding of lipid binding proteins, W391 itself seems to be important for activity. These data suggest that both interactions with lipid binding proteins and the peptide itself are important for optimal enzyme activity. | Kim JH, Ee SM, Jittiwat J, Ong ES, Farooqui AA, Jenner AM, Ong WY (2011) Increased expression of acyl-coenzyme A: cholesterol acyltransferase-1 and elevated cholesteryl esters in the hippocampus after excitotoxic injury. Neuroscience 185, 125-134 [PubMed:21514367] [show Abstract] Significant increases in levels of cholesterol and cholesterol oxidation products are detected in the hippocampus undergoing degeneration after excitotoxicity induced by the potent glutamate analog, kainate (KA), but until now, it is unclear whether the cholesterol is in the free or esterified form. The present study was carried out to examine the expression of the enzyme involved in cholesteryl ester biosynthesis, acyl-coenzyme A: cholesterol acyltransferase (ACAT) and cholesteryl esters after KA excitotoxicity. A 1000-fold greater basal mRNA level of ACAT1 than ACAT2 was detected in the normal brain. ACAT1 mRNA and protein were upregulated in the hippocampus at 1 and 2 weeks after KA injections, at a time of glial reaction. Immunohistochemistry showed ACAT1 labeling of oligodendrocytes in the white matter and axon terminals in hippocampal CA fields of normal rats, and loss of staining in neurons but increased immunoreactivity of oligodendrocytes, in areas affected by KA. Gas chromatography-mass spectrometry analyses confirmed previous observations of a marked increase in level of total cholesterol and cholesterol oxidation products, whilst nuclear magnetic resonance spectroscopy showed significant increases in cholesteryl ester species in the degenerating hippocampus. Upregulation of ACAT1 expression was detected in OLN93 oligodendrocytes after KA treatment, and increased expression was prevented by an antioxidant or free radical scavenger in vitro. This suggests that ACAT1 expression may be induced by oxidative stress. Together, our results show elevated ACAT1 expression and increased cholesteryl esters after KA excitotoxicity. Further studies are necessary to determine a possible role of ACAT1 in acute and chronic neurodegenerative diseases. | Ioriya K, Kino K, Horisawa S, Nishimura T, Muraoka M, Noguchi T, Ohashi N (2006) Pharmacological profile of SMP-797, a novel acyl-coenzyme a: cholesterol acyltransferase inhibitor with inducible effect on the expression of low-density lipoprotein receptor. Journal of cardiovascular pharmacology 47, 322-329 [PubMed:16495773] [show Abstract] We investigated the pharmacological profile of SMP-797, a novel hypocholesterolemic agent. SMP-797 showed inhibitory effects on acyl-coenzyme A: cholesterol acyltransferase (ACAT) activities in various microsomes and in human cell lines, and hypocholesterolemic effects in rabbits fed a cholesterol-rich diet and hamsters fed a normal diet. In hamsters, the reduction of total cholesterol level by SMP-797 was mainly due to the decrease of low-density lipoprotein (LDL) cholesterol level rather than that of very low-density lipoprotein (VLDL) cholesterol level. Interestingly, SMP-797 increased the hepatic low-density lipoprotein receptor expression in vivo when it decreased the low-density lipoprotein cholesterol level. SMP-797 also increased low-density lipoprotein receptor expression in HepG2 cells like atorvastatin, an HMG-CoA reductase inhibitor, although other acyl-coenzyme A: cholesterol acyltransferase inhibitor had no effect. In addition, SMP-797 had no effect on cholesterol synthesis in HepG2 cells. These results suggested that the increase of low-density lipoprotein receptor expression by SMP-797 was independent of its acyl-coenzyme A: cholesterol acyltransferase inhibitory action and did not result from the inhibition of hepatic cholesterol synthesis. In conclusion, these results suggest that SMP-797 is a novel hypocholesterolemic agent showing a cholesterol-lowering effect in which the increase of hepatic low-density lipoprotein receptor expression as well as the inhibition of acyl-coenzyme A: cholesterol acyltransferase is involved. | Rudel LL, Lee RG, Cockman TL (2001) Acyl coenzyme A: cholesterol acyltransferase types 1 and 2: structure and function in atherosclerosis. Current opinion in lipidology 12, 121-127 [PubMed:11264983] [show Abstract] Two enzymes are responsible for cholesterol ester formation in tissues, acyl coenzyme A:cholesterol acyltransferase types 1 and 2 (ACAT1 and ACAT2). The available evidence suggests different cell locations, membrane orientations, and metabolic functions for each enzyme. ACAT1 and ACAT2 gene disruption experiments in mice have shown complementary results, with ACAT1 being responsible for cholesterol homeostasis in the brain, skin, adrenal, and macrophages. ACAT1 -/- mice have less atherosclerosis than their ACAT1 +/+ counterparts, presumably because of the decreased ACAT activity in the macrophages. By contrast, ACAT2 -/- mice have limited cholesterol absorption in the intestine, and decreased cholesterol ester content in the liver and plasma lipoproteins. Almost no cholesterol esterification was found when liver and intestinal microsomes from ACAT2 -/- mice were assayed. Studies in non-human primates have shown the presence of ACAT1 primarily in the Kupffer cells of the liver, in non-mucosal cell types in the intestine, and in kidney and adrenal cortical cells, whereas ACAT2 is present only in hepatocytes and in intestinal mucosal cells. The membrane topology for ACAT1 and ACAT2 is also apparently different, with ACAT1 having a serine essential for activity on the cytoplasmic side of the endoplasmic reticulum membrane, whereas the analogous serine is present on the lumenal side of the endoplasmic reticulum for ACAT2. Taken together, the data suggest that cholesterol ester formation by ACAT1 supports separate functions compared with cholesterol esterification by ACAT2. The latter enzyme appears to be responsible for cholesterol ester formation and secretion in lipoproteins, whereas ACAT1 appears to function to maintain appropriate cholesterol availability in cell membranes. | Gregersen N, Andresen BS, Corydon MJ, Corydon TJ, Olsen RK, Bolund L, Bross P (2001) Mutation analysis in mitochondrial fatty acid oxidation defects: Exemplified by acyl-CoA dehydrogenase deficiencies, with special focus on genotype-phenotype relationship. Human mutation 18, 169-189 [PubMed:11524729] [show Abstract] Mutation analysis of metabolic disorders, such as the fatty acid oxidation defects, offers an additional, and often superior, tool for specific diagnosis compared to traditional enzymatic assays. With the advancement of the structural part of the Human Genome Project and the creation of mutation databases, procedures for convenient and reliable genetic analyses are being developed. The most straightforward application of mutation analysis is to specific diagnoses in suspected patients, particularly in the context of family studies and for prenatal/preimplantation analysis. In addition, from these practical uses emerges the possibility to study genotype-phenotype relationships and investigate the molecular pathogenesis resulting from specific mutations or groups of mutations. In the present review we summarize current knowledge regarding genotype-phenotype relationships in three disorders of mitochondrial fatty acid oxidation: very-long chain acyl-CoA dehydrogenase (VLCAD, also ACADVL), medium-chain acyl-CoA dehydrogenase (MCAD, also ACADM), and short-chain acyl-CoA dehydrogenase (SCAD, also ACADS) deficiencies. On the basis of this knowledge we discuss current understanding of the structural implications of mutation type, as well as the modulating effect of the mitochondrial protein quality control systems, composed of molecular chaperones and intracellular proteases. We propose that the unraveling of the genetic and cellular determinants of the modulating effects of protein quality control systems may help to assess the balance between genetic and environmental factors in the clinical expression of a given mutation. The realization that the effect of the monogene, such as disease-causing mutations in the VLCAD, MCAD, and SCAD genes, may be modified by variations in other genes presages the need for profile analyses of additional genetic variations. The rapid development of mutation detection systems, such as the chip technologies, makes such profile analyses feasible. However, it remains to be seen to what extent mutation analysis will be used for diagnosis of fatty acid oxidation defects and other metabolic disorders. |
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