Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.4.1.2 (acetyl-CoA carboxylase)
 2,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipid synthesis as measured by the incorporation of acetate or 3H2O into slices of foetal liver, is much higher than in slices of adult liver and shows a peak at about two-thirds of gestation. At this time the synthesis from glucose was low and reached a peak 10 days later. The changes in the activity of ATP citrate lyase, which mirrored acetate incorporation, and the effect of glucose and pyruvate on acetate corporation into lipid suggests that some of the lipid synthesis occurs via intramitochondrial acetyl-CoA production from acetate. Despite this, lipid synthesis was not inhibited by (-)-hydroxycitrate. The low rate of synthesis from glucose at two-thirds of gestation is ascribed to the low activity of pyruvate carboxylase at this time and a role for a phosphoenolpyruvate carboxykinase in providing oxaloacetate for lipogenesis is proposed. The activity of fatty acid synthetase broadly agreed with the changes in lipid synthesis, whereas the activity of acetyl-CoA carboxylase was barely sufficient to account for the rates of lipid synthesis in vivo. Acetate and short-chain fatty acids are likely to be the major precursors for lipid synthesis in vivo.
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PMID:Lipid biosynthesis in liver slices of the foetal guinea pig. 0 15

Biotin localized in barley chloroplast lamellae is covalently bound to a single protein with an approximate molecular weight of 21 000. It contains one mole of biotin per mole of protein and functions as a carboxyl carrier in the acetyl-CoA carboxylase reaction. The protein was obtained by solubilization of the lamellae in phenol/acetic acid/8 M urea. Feeding barley seedlings with [14C]-biotin revealed that the vitamin is not degraded into respiratory substrates by the plant, but is specifically incorporated into biotin carboxyl carrier protein.
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PMID:Biotin carboxyl carrier protein in barley chloroplast membranes. 23 45

Studies were initiated to compare glucose and lipid metabolism in vitro in subcutaneous adipose tissue of mature sheep and cattle. Mean adipocyte volume was significantly less in subcutaneous adipose tissue of sheep than in adipose tissue from cattle. The presence of acetate and lactate in the incubation medium increased total glucose utilization two- to three-fold in ovine adipose tissue, but had no effect on total glucose utilization in adipose tissue from cattle. Acetate provided 72-82% of the acetyl units to lipogenesis, depending on species and substrate concentration. There were no significant (P greater than 0.05) differences in the contribution of the pentose cycle to the provision of reducing equivalents to fatty acid biosynthesis, based on the incorporation of label from [3-3H]glucose into fatty acids. In ovine adipose tissue, acetyl-CoA carboxylase appeared to be rate-limiting to lipogenesis, while in bovine subcutaneous adipose tissue, the activity of fatty acid synthetase may have been the limiting step in lipogenesis. In addition, the low activity of ATP-citrate lyase, especially relative to aconitate hydratase, probably limited the conversion of lactate to fatty acids in ovine adipose tissue. It is unlikely that ATP-citrate lyase activity was rate-limiting to lipogenesis from lactate in bovine adipose tissue. The data indicate that extending the results obtained from adipose tissue from one species to lipid metabolism in ruminants in general may not be valid.
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PMID:Comparisons of lipogenesis and glucose metabolism between ovine and bovine adipose tissues. 374 65

Octanoate and N6,O2'-dibutyryl adenosine 3',5'-monophosphate (dibutyryl cyclic AMP) cause a marked inhibition of net glucose utilization and lactate and pyruvate accumulation by hepatocytes isolated from meal-fed rats. Acetate is much less effective as an inhibitor of glycolysis. Fatty acid synthesis, as measured by tritiated water incorporation, is inhibited by dibutyryl cyclic AMP, whereas it is stimulated by 10 mM acetate and 1 mM octanoate. Stimulation of fatty acid synthesis by 1 mM octanoate, however, is lost paradoxically at higher concentrations of octanoate. Rates of fatty acid synthesis estimated by [1-14C]octanoate incorporation were consistently higher than rates calculated on the basis of tritiated water incorporation, raising the question as to which is the better index of the rate of de novo fatty acid synthesis. The effects of octanoate were studied because it was reasoned that this fatty acid should not inhibit acetyl-CoA carboxylase but should inhibit glycolysis and supply acetyl-CoA for lipogenesis. This was found to be the case, proving that glycolytic activity is not necessary for rapid rates of de novo fatty acid synthesis by liver.
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PMID:Effects of octanoate and acetate upon hepatic glycolysis and lipogenesis. 631 44

Spiramycin biosynthesis in Streptomyces ambofaciens was stimulated in the presence of valine or by sequential addition of some short-chain fatty acids to a culture medium containing an ammonium salt as source of nitrogen. Acetate kinase and acetyl-CoA carboxylase, enzymes that catalysed the formation of precursors of spiramycin biosynthesis (acetyl-CoA and malonyl-CoA), were detected during the active growth and antibiotic production phases. In this latter phase a higher level of acetyl-CoA carboxylase activity was observed with valine (1.02 mumol.min-1.mg protein-1) than with ammonium (0.05 mumol.min-1.mg protein-1) as nitrogen source, while the evolution and the level of acetate kinase activity were the same in both media. Successive addition of acetate and isobutyrate stimulated highly and weakly the acetyl-CoA carboxylase and acetate kinase activity, respectively.
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PMID:Relationship between valine, fatty acids, and spiramycin biosynthesis in Streptomyces ambofaciens. 792 89

The function of acyl carrier protein (ACP) in mitochondria isolated from pea leaves has been investigated. When pea leaf mitochondria were labeled with [2-14C] malonic acid in vitro, radioactivity was incorporated into fatty acids, and, simultaneously, ACP was acylated. [1-14C]Acetate was much less effective as a precursor for fatty acid synthesis, suggesting that mitochondria do not possess acetyl-CoA carboxylase. The incorporation of radioactivity from [2-14C]malonate into fatty acids and the labeling of ACP were inhibited by cerulenin and required ATP and Mg2+. These findings indicate that plant mitochondria contain not only ACP, but all enzymes required for de novo fatty acid synthesis. Over 30% of the radioactive products from pea mitochondria labeled with [2-14C]malonate were recovered in H protein, which is a subunit of glycine decarboxylase and contains lipoic acid as an essential constituent. In similar experiments, the H protein of Neurospora mitochondria was also labeled by [2-14C]malonate. The labeling of pea H protein was inhibited by addition of cerulenin into the assay medium. Together, these findings indicate that ACP is involved in the de novo synthesis of fatty acids in plant mitochondria and that a major function of this pathway is production of lipoic acid precursors.
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PMID:Why do mitochondria synthesize fatty acids? Evidence for involvement in lipoic acid production. 903 98

The aim of the present study was to investigate the hepatic regulation and beta-oxidation of long-chain fatty acids in peroxisomes and mitochondria, after 3-thia- tetradecylthioacetic acid (C14-S-acetic acid) treatment. When palmitoyl-CoA and palmitoyl-L-carnitine were used as substrates, hepatic formation of acid-soluble products was significantly increased in C14-S-acetic acid treated rats. Administration of C14-S-acetic acid resulted in increased enzyme activity and mRNA levels of hepatic mitochondrial carnitine palmitoyltransferase (CPT)-II. CPT-II activity correlated with both palmitoyl-CoA and palmitoyl-L-carnitine oxidation in rats treated with different chain-length 3-thia fatty acids. CPT-I activity and mRNA levels were, however, marginally affected. The hepatic CPT-II activity was mainly localized in the mitochondrial fraction, whereas the CPT-I activity was enriched in the mitochondrial, peroxisomal, and microsomal fractions. In C14-S-acetic acid-treated rats, the specific activity of peroxisomal and microsomal CPT-I increased, whereas the mitochondrial activity tended to decrease. C14-S-Acetyl-CoA inhibited CPT-I activity in vitro. The sensitivity of CPT-I to malonyl-CoA was unchanged, and the hepatic malonyl-CoA concentration increased after C14-S-acetic acid treatment. The mRNA levels of acetyl-CoA carboxylase increased. In hepatocytes cultured from palmitic acid- and C14-S-acetic acid-treated rats, the CPT-I inhibitor etomoxir inhibited the formation of acid-soluble products 91 and 21%, respectively. In contrast to 3-thia fatty acid treatment, eicosapentaenoic acid treatment and starvation increased the mitochondrial CPT-I activity and reduced its malonyl-CoA sensitivity. Palmitoyl-L-carnitine oxidation and CPT-II activity were, however, unchanged after either EPA treatment or starvation. The results from this study open the possibility that the rate control of mitochondrial beta-oxidation under mitochondrion and peroxisome proliferation is distributed between an enzyme or enzymes of the pathway beyond the CPT-I site after 3-thia fatty acid treatment. It is suggested that fatty acids are partly oxidized in the peroxisomes before entering the mitochondria as acylcarnitines for further oxidation.
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PMID:3-Thia fatty acid treatment, in contrast to eicosapentaenoic acid and starvation, induces gene expression of carnitine palmitoyltransferase-II in rat liver. 1038 Jan 16

Carnitine palmitoyltransferase 1beta (CPT-1beta) is a key regulator of the beta oxidation of long-chain fatty acids in skeletal muscle and therefore a potential therapeutic target for diseases associated with defects in lipid metabolism such as obesity and type 2 diabetes. C75 [4-methylene-2-octyl-5-oxo-tetrahydro-furan-3-carboxylic acid] is an alpha-methylene-butyrolactone that has been characterized as both an inhibitor of fatty acid synthase and more recently, an activator of CPT-1 (Thupari et al., 2002). Using human CPT-1beta expressed in the yeast Pichia pastoris, we demonstrate that C75 can activate the skeletal muscle isoform of CPT-1 and overcome inactivation of the enzyme by malonyl CoA, an important physiological repressor of CPT-1, and the malonyl CoA mimetic Ro25-0187 [{5-[2-(naphthalen-2-yloxy)-ethoxy]-thiophen-2-yl}-oxo-acetic acid]. We also show that C75 can activate CPT-1 in intact hepatocytes to levels similar to those achieved with inhibition of acetyl-CoA carboxylase, the enzyme that produces malonyl CoA. Finally, we demonstrate that concentrations of C75 sufficient for activation of CPT-1 do not displace bound malonyl CoA. We conclude that CPT-1 is an activator of human CPT-1beta and other CPT-1 isoforms but that it does not activate CPT-1 through antagonism of malonyl CoA binding.
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PMID:C75 [4-methylene-2-octyl-5-oxo-tetrahydro-furan-3-carboxylic acid] activates carnitine palmitoyltransferase-1 in isolated mitochondria and intact cells without displacement of bound malonyl CoA. 1535 15

Chloroplasts isolated from immature leaves of spinach (Spinacia oleracea) differ in enzyme levels from those isolated from mature leaves. On a chlorophyll basis, immature chloroplast preparations had 5- to 6-fold higher capacity to synthesize fatty acids from 2-(14)C-acetate compared to plastids isolated from mature leaves. This difference was correlated with higher activities for the enzymes, acetyl coenzyme A synthetase, malonyl coenzyme A synthetase, acetyl coenzyme A carboxylase, and oleyl coenzyme A transferase in plastid pressates obtained from immature leaves. Disrupted chloroplast preparations from both mature and immature leaves retained the ability to incorporate 2-(14)C-acetate into fatty acids in a pattern similar to that by isolated chloroplasts. 2-(14)C-Acetate, 2-(14)C-acetyl coenzyme A, 2-(14)C-malonate, and 1,3-(14)C malonyl coenzyme A were readily incorporated into a number of fatty acids. Moreover, the synthesis of oleate by chloroplast pressates from these substrates was strongly inhibited by KCN, flavin adenine mononucleotides and dinucleotides, and anaerobic conditions, while linolenic acid synthesis was unaffected by these compounds.
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PMID:Fat Metabolism in Higher Plants: LVII. A Comparison of Fatty Acid-Synthesizing Enzymes in Chloroplasts Isolated from Mature and Immature Leaves of Spinach. 1665 18

In this report, concentration of malonic acid and acetic acid produced in Escherichia coli were investigated by the expression of acetyl-CoA carboxylase genes (accs) and a malonyl-CoA:ACP transacylase gene (fabD). Both malonyl-CoA and acetyl-CoA are essential intermediate metabolites in the fatty acid biosynthetic pathway, and are reversibly transformed to malonic acid and acetic acid, respectively in the cell. Acetyl-CoA is converted to malonic-CoA by acetyl-CoA carboxylases (Accs), which are composed of 3 different subunits (AccA, AccB, and AccC), and the resulting malonyl-CoA is then converted to malonyl-[acp] by malonyl-CoA:ACP transacylase (FabD). In this study, these genes were separately cloned, and the influences of overexpression of 4 different genes on the concentration of malonic acid and acetic acid were analyzed. Compared with the wild type E. coli, a recombinant strain containing 3 acc genes together showed a 41.03% enhanced malonic acid production, and a 4.29-fold increased ratio of malonic acid to acetic acid.
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PMID:An analysis of the concentration change of intermediate metabolites by gene manipulation in fatty acid biosynthesis. 2266 93


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