Disease relevance of CoA

• The model also explains underlying biochemical differences between patients with Reye syndrome and medium-chain acyl CoA dehydrogenase deficiency, another disorder of fatty acid metabolism [1].
• Interaction between succinyl CoA synthetase and the heme-biosynthetic enzyme ALAS-E is disrupted in sideroblastic anemia [2].
• Formyl-CoA transferase catalyses transfer of CoA from formate to oxalate in the first step of oxalate degradation by Oxalobacter formigenes, a bacterium present in the intestinal flora which is implicated in oxalate catabolism in mammals [3].
• Despite similar degrees of left ventricular systolic hypertension shortening characteristics are usually greater in patients with congenital valvular aortic stenosis (VAS) than in patients with coarctation of the aorta (CoA) [4].
• In cultured hepatoma cells, HCV RNA replication was disrupted by treatment with lovastatin, an inhibitor of 3-hydroxy-3-methyglutaryl CoA reductase, or with an inhibitor of protein geranylgeranyl transferase I, each of which induced the dissolution of the HCV replication complex [5].

Psychiatry related information on CoA

• Younger age at presentation, history of unexplained sibling death, a previous episode of lethargy, hypoglycemia or acidosis precipitated by fasting stress and only mildly elevated serum transaminases with normal or only mildly prolonged prothrombin time may all suggest an acyl CoA dehydrogenase deficiency [6].
• A 31-year-old man with adult onset chorea and dementia had propionic acidemia due to propionyl CoA carboxylase deficiency [7].
• Recent epidemiological studies suggest that inhibitors of 3-hydroxy-3-methyl-glutaryl CoA reductase, so-called statins, are effective in lowering the prevalence of Alzheimer's disease [8].
• The risk of CoA was not associated with seasonal variation, maternal smoking, alcohol consumption, or use of deodorants [9].
• BACKGROUND: The gene encoding fatty acid CoA ligase 4 (FACL4) is mutated in families with non-specific X linked mental retardation (MRX) and is responsible for cognitive impairment in the contiguous gene syndrome ATS-MR (Alport syndrome and mental retardation), mapped to Xq22 [10].

High impact information on CoA

• Using an inhibitor of long-chain acyl-CoA synthetase, we demonstrate that the fatty acid has to be activated by CoA to stimulate transport [11].
• Five cell lines (derived from three families) were able to catalyze acetylation of the lysosomal membrane and to carry out acetyl-CoA/CoA exchange, whereas a sixth cell line was devoid of this activity [12].
• In this report, we describe the design, synthesis, and application of peptide CoA conjugates as selective HAT inhibitors for the transcriptional coactivators p300 and PCAF [13].
• This augmenting effect of Ser-10 phosphorylation on acetylation by yGcn5 was lost by substitution of alanine for arginine 164 [Gcn5(R164A)], a residue close to Ser-10 in the structure of the ternary tGcn5/CoA/histone H3 complex [14].
• Our screening led to the isolation of the beta subunit of human ATP-specific succinyl CoA synthetase (SCS-betaA) [2].

Chemical compound and disease context of CoA

• In biotin-responsive multiple carboxylase deficiency, a characteristic organic aciduria reflects in vivo deficiency of mitochondrial propionyl CoA carboxylase, 3-methylcrotonyl CoA carboxylase, and pyruvate carboxylase [15].
• Mycobacterium tuberculosis contains >20 enzymes that require activation by transfer of the 4'-phosphopantetheine moiety of CoA onto a conserved serine residue, a posttranslational modification catalyzed by 4'-phosphopantetheinyl transferases (PPTases) [16].
• The effects of competitive inhibition of hydroxymethylglutaryl coenzyme A (HMG CoA) reductase by compactin on the in vitro proliferation of peripheral blood myeloid leukemia cells were studied using the cells from 45 patients with acute myeloid leukemia or chronic myelogenous leukemia in blast phase [17].
• The presence of succinyl-coenzyme A:acetoacetate CoA transferase (CoA transferase) (EC 2.8.3.5), an initiator of ketone body utilization in nonhepatic tissue, was examined in liver from normal, partly hepatectomized, neonatal, and tumor-bearing rats, as well as in a series of transplantable rat hepatomas ranging widely in growth rate [18].
• Hypercholesterolemic diabetic rodents exhibit hyperphagia, intestinal hypertrophy, and increased intestinal cholesterol synthesis and absorption; intestinal 3-hydroxy-3-methylglutaryl (HMG) CoA reductase activity is increased, whereas hepatic activity is unchanged or reduced [19].

Biological context of CoA

• In rat hepatocytes fenofibric acid induced acyl CoA oxidase gene expression, whereas acyl CoA oxidase mRNA remained unchanged in human hepatocytes [20].
• It is also possible that FABP, by effecting an intracellular compartmentalization of fatty acids and acyl CoA, may play a broader role in cellular lipid metabolism [21].
• Genetic mapping of the trait placed the gene on chromosome 5 near Acads, a gene encoding the short chain acyl CoA dehydrogenase, which is mutated in BALB/cByJ mice [22].
• Confirmation of the importance of fatty acid oxidation to thermogenesis came from our finding that mice carrying the targeted inactivation of the long chain acyl CoA dehydrogenase gene (Acadl) are also sensitive to the cold [22].
• Formyl-CoA transferase encloses the CoA binding site at the interface of an interlocked dimer [3].

Anatomical context of CoA

• When liver microsomes were incubated with DCA, the pattern of inhibition of reductase activity was noncompetitive for both HMG CoA (inhibition constant [Ki] 11.8 mM) and NADPH (Ki 11.6 mM) [23].
• Skeletal muscle CoA and carnitine metabolism were investigated in six human volunteers at rest and after exhaustive exercise under normoxic and hypoxic conditions [24].
• These studies were performed to determine whether oxidation of acetoacetate by isolated rat heart mitochondria results in a fall in intramitochondrial nonesterified CoA [CoASH] and whether increasing the available CoA improves contractile performance in hearts oxidizing acetoacetate [25].
• Activities of propionyl CoA carboxylase, beta-methylcrotonyl CoA carboxylase, and pyruvate carboxylase in cultured fibroblasts were normal [26].
• 3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase is anchored to the endoplasmic reticulum (ER) membrane by a hydrophobic NH2-terminal domain that contains seven apparent membrane-spanning regions and a single N-linked carbohydrate chain [27].

Associations of CoA with other chemical compounds

• The elevations in mRNA for 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) synthase and HMG CoA reductase were especially marked (13-fold and 75-fold, respectively) [28].
• Inhibition by glyoxylate was also noncompetitive for both HMG CoA (Ki 1.2 mM) and NADPH (Ki 2.7 mM) [23].
• Since exercise did not significantly affect the skeletal muscle CoA radical (CoASH), total acid-soluble, or total CoA contents, the increase in the acetyl-CoA content was at the expense of short-chain acyl-CoAs different from acetyl-CoA [24].
• The rate of oxidation of pristanic acid was reduced in affected cell lines from all of the families with inherited defects in peroxisomal beta-oxidation, thus excluding the possibility of a defective acyl CoA oxidase [29].
• Mevalonolactone inhibited hydroxymethyl-glutaryl CoA reductase activity 90% but did not increase bile-acid synthesis and cholesterol 7 alpha-hydroxylase activity [30].

Gene context of CoA

• Our recent studies of the 455-amino acid Saccharomyces cerevisiae acyltransferase (Nmt1p) suggested that its mechanism of catalysis is ordered Bi Bi with myristoyl-CoA binding occurring prior to binding of peptide and release of CoA occurring prior to release of the myristoyl-peptide [31].
• Also, two methods were developed to measure the binding affinities of AcCoA/CoA for GCN5 [32].
• Human GCN5 and the N-terminal deletion mutant of PCAF are stabilized equally well by preincubation with either CoA or acetyl-CoA, while intact PCAF is better stabilized by acetyl-CoA than by CoA [33].
• Enzyme activity measurements with expressed ACOT4 and ACOT8 show that both enzymes hydrolyze CoA esters of dicarboxylic acids with high activity but with strikingly different specificities [34].
• When tested in a microsomal assay, Lac1p and Lag1p had a strong preference for C26:0-CoA over C24:0-CoA, C20-CoA, and C16-CoA, whereas some human homologues preferred C24:0-CoA and CoA derivatives with shorter fatty acids [35].

Analytical, diagnostic and therapeutic context of CoA

• In-vivo and cell-culture experiments have shown that lowering the plasma cholesterol concentration or intervening in the mevalonate pathway with 3-hydroxy-3-methylglutaryl (HMG) CoA reductase inhibitors decreases tumour growth [36].
• BACKGROUND: The study objective was to examine the vascular wall changes caused by balloon dilation of coarctation of the aorta (CoA) acutely and at short-term follow-up using intravascular ultrasound imaging [37].
• Eleven patients with VAS (ages 6 to 41 years) and 11 with CoA were matched for age, body surface area, and peak systolic ejection gradient [4].
• We have introduced three heterologous genes into T. vaginalis by electroporation and have used the 5' and 3' untranslated regions of the endogenous gene alpha-succinyl CoA synthetase B (alpha-SCSB) to drive transcription of these genes [38].
• Sequence alignment of the human SCOT peptides with other known CoA transferases revealed several conserved regions of potential functional importance [39].

References