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

Administration of triamcinolone or dexamethasone to rats led to a prompt, marked and persistent rise in liver acetyl-CoA carboxylase activity. The activity of fatty acid synthetase increased to a lesser extent and after a more prolonged glucocorticoid treatment, whereas the changes in that of NADP-malate dehydrogenase and ATP-citrate lyase were not appreciable. The overall channeling of [1-14-C]acetyl-CoA to fatty acids was enhanced. The triamcinolone effect on acetyl-CoA carboxylase activity appeared to be dependent on the coincident hyperinsulinemia since it was not obtained in alloxan-diabetic rats, whereas the alanine-aminotransferase-inducing effect of this hormone was additive to that of insulin deficiency. In adipose tissue triamcinolone treatment caused a reduction in the activity of all lipogenesis enzymes and blunted their response to insulin administration. The antagonism of glucocorticoids toward insulin, selectively modulating the responses of the insulin-sensitive enzymes in liver and adipose tissue is discussed. The rise in hepatic lipogenic capacity, through the retention of the ability of insulin to induce acetyl-CoA carboxylase, may be physiologically important in restraining the ketogenesis from acetyl-CoA despite the increased fat utilization during glucocorticoid excess.
 ...
PMID:Modulation of the activity of insulin-dependent enzymes of lipogenesis by glucocorticoids. 23 62

The hyperinsulinaemic-glucose-clamp technique, in combination with measurement of glucose turnover in conscious unrestrained rats, was used to assess the effects of nutritional status on insulin sensitivity in vivo and glucose metabolism. Liver, heart and quadriceps skeletal-muscle glycogen content and activities of pyruvate dehydrogenase (PDH) and glycogen synthase were measured both basally and at the end of a 2.5 h glucose clamp (insulin 85 munits/h) in rats 6, 24 and 48 h after food withdrawal. Clamp glucose requirement and glucose turnover were unchanged by fasting. Activation of glycogen synthase and glycogen deposition in liver and skeletal muscle during the clamps were also not impaired in rats after a prolonged fast. By contrast with skeletal muscle, activation of cardiac-muscle glycogen synthase and glycogen deposition during the clamps were markedly impaired by 24 h of fasting and were undetectable at 48 h. Skeletal-muscle PDH activity fell with more prolonged fasting (6 h, 15.3 +/- 3.4%; 24 h, 4.7 +/- 0.7%; 48 h, 4.3 +/- 0.6% active; P less than 0.005), but at 24 and 48 h was stimulated by the clamp to values unchanged by the duration of fasting. Stimulation of cardiac PDH activity by the clamp was, however, impaired in rats fasted for 24 or 48 h. Basal hepatic PDH did not change significantly with fasting (6 h, 5.3 +/- 1.1%; 24 h, 4.6 +/- 0.7%; 48 h, 3.9 +/- 0.5%), and, although it could be partly restored at 24 h, very little stimulation occurred at 48 h. Hepatic pyruvate kinase and acetyl-CoA carboxylase activity were both stimulated by the clamps, and this was not impaired with more prolonged fasting. During the glucose clamps, blood concentrations of lactate, pyruvate and alanine were increased to a greater extent in rats fasted for 24 and 48 h than in rats studied 6 h after food withdrawal. The findings suggest that, although sensitivity to insulin of whole-body glucose disposal is unchanged with fasting, there may be qualitative differences in the metabolism of glucose.
 ...
PMID:Effect of nutritional status on insulin sensitivity in vivo and tissue enzyme activities in the rat. 249 4

The biotin-binding site of acetyl-CoA carboxylase from rat was characterized as to its amino acid sequence and relative position in the enzyme molecule. Biotin binds to the lysyl residue in the tetrapeptide Val-Met-Lys-Met; this tetrapeptide is located in close proximity to the NH2 terminus. In all other biotin-containing enzymes, the conserved tetrapeptide Ala-Met-Lys-Met is the counterpart to that of rat acetyl-CoA carboxylase; and the lysyl residue is 35 residues from the COOH terminus. To examine the significance of these unusual features of the biotinylation site of animal acetyl-CoA carboxylase, cDNA fragments were expressed in a bacterial system and the effects of specific site-directed mutagenesis were examined. Replacement of Val by Ala in the conserved tetrapeptide abolished biotinylation of the expressed protein. However, introduction of a termination codon at residue 36, in such a way that the distance between the lysine on which biotin binds and the COOH-terminal amino acid was 35 residues and the penultimate amino acid was the hydrophobic residue leucine, increased the efficiency of biotinylation, provided a substantial portion of the NH2-terminal peptide was removed.
 ...
PMID:Analysis of the biotin-binding site on acetyl-CoA carboxylase from rat. 256 68

1. We have synthesized two peptides, one based on the exact sequence around the unique site (Ser79) for the AMP-activated protein kinase on rat acetyl-CoA carboxylase (SSMS peptide) and another in which the serine residue corresponding to the site for cyclic-AMP-dependent protein kinase (Ser77) was replaced by alanine (SAMS peptide). 2. Both peptides were phosphorylated with similar kinetics by the AMP-activated protein kinase, but only the SSMS peptide was a substrate for cyclic-AMP-dependent protein kinase. The SAMS peptide was not phosphorylated by any of five other purified protein kinases tested. 3. The Km of AMP-activated protein kinase for the SAMS peptide is higher than that for acetyl-CoA carboxylase, but the Vmax for peptide phosphorylation is 2.5 times higher than that of its parent protein. This peptide therefore gives a convenient and sensitive assay for the AMP-activated protein kinase. 4. Acetyl-CoA-carboxylase kinase and peptide kinase activities copurify through six steps from a post-mitochondrial supernatant of rat liver, showing that the SAMS peptide is a specific substrate for the AMP-activated protein kinase in this tissue. We could not demonstrate AMP-dependence of the kinase activity in crude preparations, apparently due to endogenous AMP remaining bound to the enzyme. However, 8-bromoadenosine 5-monophosphate (Br8AMP) is a partial agonist at the allosteric (AMP) site, and inhibition by 2 mM Br8AMP can be used to test that one is measuring the AMP-stimulated form of the kinase. 5. Using this approach, we have examined the kinase activity in nine different rat tissues, plus a mouse macrophage cell line, and find that there is a correlation between tissues expressing significant levels of peptide kinase activity and those active in the synthesis or storage of lipids. 6. We also use the peptide assay to show that cyclic AMP-dependent protein kinase does not activate purified AMP-activated protein kinase, and does not affect the activation of partially purified AMP-activated protein kinase by endogenous kinase kinase.
 ...
PMID:Tissue distribution of the AMP-activated protein kinase, and lack of activation by cyclic-AMP-dependent protein kinase, studied using a specific and sensitive peptide assay. 257 67

Acetyl-coenzyme A carboxylase (Ac-CoA carboxylase; EC 6.4.1.2) catalyzes the rate-limiting reaction in long-chain fatty acid biosynthesis. To investigate the mechanism of genetic control of expression of Ac-CoA carboxylase and the relationship between its structure and function, cDNA clones for Ac-CoA carboxylase were isolated. The complete coding sequence contains 7035 bases; it encodes a polypeptide chain of 2345 amino acids having a Mr of 265,220. The sequences of several CNBr peptides of Ac-CoA carboxylase were localized within the predicted protein sequence as were those peptides that contain the sites for phosphorylation. The deduced protein contains one putative site for biotinylation in the NH2-terminal half. The "conserved" biotinylation site peptide, Met-Lys-Met, is preceded by valine, whereas alanine is found in a similar position in all other known biotin-containing proteins. The primary sequences of Ac-CoA carboxylase and carbamoyl phosphate synthetase exhibit substantial identity.
 ...
PMID:Structure of the coding sequence and primary amino acid sequence of acetyl-coenzyme A carboxylase. 290 Oct 88

The apo 1.3S subunit of transcarboxylase contains the sequence Ala-87-Met-88-Lys-89-Met-90, and it is Lys-89 that is biotinated. This sequence is highly conserved in all the biotin enzymes that have been sequenced (with the exception of acetyl-CoA carboxylase from chicken liver, which has Val in place of Ala). The role of Met-88 and Met-90 in specifying Lys-89 for biotination by synthetase was examined by site-directed mutagenesis. Genes of the 1.3S subunit coding for Thr-88, Leu-88, or Leu-90 were generated by oligonucleotide-directed in vitro mutagenesis and expressed in Escherichia coli. The mutated apo 1.3S subunits were isolated and the biotination by homogeneous synthetase from Propionibacterium shermanii was compared with that of the apo wild-type subunit. The Vmax for the apo mutants was the same as that for the apo wild type, but when Leu was substituted for Met-88 or Met-90, the Km for the mutant was lower than that of the wild-type or mutant Thr-88. The activity of the synthetase of E. coli was determined by an in vivo assay. During the early log phase of growth, a smaller portion of mutants Thr-88 and Leu-90 was biotinated than with the wild-type or mutant Leu-88. When the cultures progressed to stationary phase, mutants and the wild type were biotinated to the same extent. The overall results show that Met-88 and Met-90 are not required for biotination of the apo 1.3S subunit by the synthetases.
 ...
PMID:Effect of mutations at Met-88 and Met-90 on the biotination of Lys-89 of the apo 1.3S subunit of transcarboxylase. 313 Nov 74

Biotin-dependent carboxylases require covalently bound biotin for enzymatic activity. The biotin is attached through a lysine residue, which in a number of bacterial, avian, and mammalian carboxylases, is found within the conserved sequence Ala-Met-Lys-Met. We have determined the partial nucleotide sequence of cDNA clones for human propionyl-CoA carboxylase and pyruvate carboxylase. The predicted amino acid sequence of both these proteins contains the conserved tetrapeptide 35 residues from the carboxy terminus. In addition, both proteins contain the tripeptide, Pro-Met-Pro, 26 residues toward the amino terminus from the biotin attachment site. The overall amino acid homology through this region is 43%. Similar findings have been made for the biotin-containing polypeptides of transcarboxylase of Propionibacterium shermanii and acetyl-CoA carboxylase of Escherichia coli (W. L. Maloy, B. U. Bowien, G. K. Zwolinski, K. G. Kumar, and H. G. Wood (1979) J. Biol. Chem. 254, 11615-11622). The implications of this sequence conservation with regard to the function and evolution of biotin-dependent carboxylases is discussed. We propose that the 60 amino acids surrounding the biotin site are bounded by a proline "hinge" and the carboxy terminus has remained conserved as a result of constraints imposed by biotinylation of the enzyme.
 ...
PMID:Sequence homology around the biotin-binding site of human propionyl-CoA carboxylase and pyruvate carboxylase. 355 48

A biotin-containing hexapeptide Ac-Glu-Ala-Met-Bct-Met-Met (1) that represents the local biotin-containing site of Escherichia coli acetyl-CoA carboxylase has been prepared by the solid phase method. Peptide 1 is carboxylated by the biotin carboxylase subunit dimer of E. coli acetyl-CoA carboxylase with the following kinetic parameters; Km 12 mM, Vmax 2.8 microM X min-1. These compare with the parameters for biotin of Km 214 mM and Vmax 28 microM X min -1. Hence, the overall reactivity (Vmax/Km) of 1 is 1.8 times greater than that of free biotin. When all methionines in 1 are replaced by alanine, the resulting peptide (2) retains a similar binding ability but with a much decreased Vmax. It was also found that peptide 3, which carries an N epsilon-benzyloxycarbonyllysine in place of biocytin in 1, decreases the Km of biotin threefold.
 ...
PMID:Importance of methionine residues in the enzymatic carboxylation of biotin-containing peptides representing the local biotinyl site of E. coli acetyl-CoA carboxylase. 614 21

Intravenous administration of a single dose (100 micrograms/kg bw) of recombinant tumour necrosis factor-alpha (TNF, cachectin) to rats increased the rate of in vitro fatty acid synthesis in interscapular brown adipose tissue (IBAT) from both glucose and alanine, without changes in the oxidation of these substrates to 14CO2. Lactate production and glycerol release were also unaffected by treatment with the cytokine. Additionally, the presence of TNF in the incubation media did not affect fatty acid synthesis, suggesting an indirect effect of the cytokine. The activities of different enzymes of glucose and alanine metabolism such as hexokinase, phosphofructokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase and alanine transaminase, did not suffer changes as a consequence of TNF administration. The same applied to the enzymatic activities involved in fatty acid synthesis such as fatty acid synthase, acetyl-CoA carboxylase and ATP-citrate lyase. Conversely, citrate levels in IBAT were increased in animals treated with TNF, suggesting that it could be the cause for the increased fatty acid synthesis in this tissue.
 ...
PMID:Metabolic effects of tumour necrosis factor-alpha on rat brown adipose tissue. 759 46

The crystal structure of Escherichia coli B glutathione synthetase (GSHase) has been determined at the optimal catalytic condition pH 7.5. The most significant structural difference from the structure at pH 6.0 is the movement of the central domain towards the N-terminal domain almost as a rigid body. As a result of this movement, new interdomain and intersubunit polar interactions are formed which stabilize the dimeric structure further. The structure of GSHase at optimal pH was compared with 294 other known protein structures in terms of the spatial arrangements of secondary structural elements. Three enzymes (D-alanine: D-alanine ligase, succinyl-CoA synthetase and the biotin carboxylase subunit of acetyl-CoA carboxylase) were found to have structures similar to the ATP-binding site of GSHase, which extends across two domains. The ATP-binding sites in these four enzymes are composed of two antiparallel beta-sheets and are different from the classic mononucleotide-binding fold. Except for these proteins, no significant structural similarity was detected between GSHase and the other ATP-binding proteins. A structural motif in the N-terminal domain of GSHase has been found to be similar to the NAD-binding fold. This structural motif is shared by a number of other proteins that bind various negatively charged molecules.
 ...
PMID:Crystal structure of glutathione synthetase at optimal pH: domain architecture and structural similarity with other proteins. 901 Sep 22


1 2 3 Next >>