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)

The responses of rat hepatic and brown adipose tissue in vivo lipogenesis to premature (15 days) and normal (21 days) weaning have been correlated to changes in the activities of acetyl-CoA carboxylase and two NADPH-producing enzymes, malic enzyme and glucose-6-phosphate dehydrogenase. Both tissues show an induction of lipogenesis in response to weaning. In the liver, lipogenic flux is closely linked to the activity of acetyl-CoA carboxylase, but not necessarily that of malic enzyme or glucose-6-phosphate dehydrogenase, whereas no such dissociation between enzyme activity and flux rate occurs in brown adipose tissue. Thyroid hormones, implicated in many physiological changes around weaning, do not seem to play a primary role in the adaptation of lipogenesis to the dietary change at this time, although a permissive role in both tissues is possible.
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PMID:Lipogenesis at the suckling-weaning transition in liver and brown adipose tissue of the rat. 612 98

Thyroid hormone regulates lipogenesis differently in rat liver and brown adipose tissue (BAT). In the hypothyroid state, lipogenesis is suppressed in liver but enhanced in BAT. Here we investigated the mechanisms underlying increased lipogenesis in hypothyroid BAT. Housing the animals at 28 degrees C decreased lipogenesis in hypothyroid BAT to euthyroid levels. Denervation resulted in a 90% reduction in lipogenesis in hypothyroid BAT such that levels were lower than in euthyroid tissue. Thyroid hormone treatment of hypothyroid rats stimulated fatty acid synthesis in denervated BAT, as in liver, but decreased it in intact BAT. Steady-state levels of mRNA encoding acetyl-CoA carboxylase, fatty-acid synthase, and spor 14 were measured in similar animals by Northern analysis. The expression of these mRNAs mirrored the lipogenic data, showing that both thyroid hormone and the sympathetic nervous system work at a pretranslational level in this tissue. These data suggest that the increased BAT lipogenesis found with hypothyroidism is mediated by the sympathetic nervous system to counter the reduction in metabolic rate in these animals.
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PMID:Regulation of brown adipose tissue lipogenesis by thyroid hormone and the sympathetic nervous system. 836 94

We have prepared a biotinylated thyrotropin receptor (TSHR-BIO), and characterized its activity in cells and when bound to solid phase (streptavidin agarose). TSHR-BIO consists of the N-terminal 725 amino acids of the human thyrotropin (TSH) receptor linked to the 87-amino acid C-terminal domain of the biotin carboxyl carrier protein subunit of Escherichia coli acetyl-CoA carboxylase. The C-terminal domain directs the efficient post-translational biotinylation of the protein. TSHR-BIO was expressed using a vaccinia virus expression system. HeLa cells infected with recombinant virus produced large amounts of TSH receptor of approximately 120,000 molecules per cell. Vaccinia virus produced TSHR-BIO was fully functional interacting with TSH (Kd of 2.3+/-0.1 x 10(-10) M) and coupling to cyclic adenosine monophosphate (cAMP) second messenger system. The expressed protein was biotinylated with high efficiency; more than 90% of TSHR-BIO was bound to streptavidin. We have shown the application of streptavidin agarose immobilized TSHR-BIO for the detection of thyroid-binding inhibiting immunoglobulines in unfractionated sera. There was a good positive correlation between the results obtained in this assay and the commercially available TRAK assay performed with solubilized porcine TSH receptor (r = 0.71; p < 0.001, in 45 sera of patients with Graves' disease and 17 normal sera).
Thyroid 1998 Jan
PMID:Expression of a biotinylated human thyrotropin receptor in HeLa cells using recombinant vaccinia virus and its application for the detection of Graves' autoantibodies. 949 46

Evidence is accumulating for roles of AMP-activated protein kinase (AMPK) in controlling glucose uptake, fatty acid oxidation and gene expression in skeletal muscle. Relatively little is known, however, about the control of expression of the AMPK subunit isoforms. Marked differences are noted in subunit expression as a function of muscle fibre type. Expression of the gamma3 subunit isoform increases in fast-twitch red fibres of the rat in response to training. All subunit isoforms are expressed to a lesser extent in rats treated with propylthiouracil (PTU; an inhibitor of thyroid hormone synthesis) for 3 weeks compared with rats given excess thyroid hormones for 3 weeks. An approx. 2-fold increase in acetyl-CoA carboxylase was observed in gastrocnemius of hyperthyroid rats compared with experimentally hypothyroid rats. Thyroid state therefore appears to be one important factor controlling expression of these proteins in skeletal muscle.
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PMID:Long-term regulation of AMP-activated protein kinase and acetyl-CoA carboxylase in skeletal muscle. 1254 81

Hyroid hormone stimulates hepatic lipogenesis in the rat by increasing the expression of relevant genes, including acetyl-CoA carboxylase and fatty acid synthase. S14 mRNA, which encodes a protein thought to be involved in lipogenesis, responds in parallel. The effects of thyroid hormone on lipogenesis in white and brown adipose tissue are less clear, and may be complicated by indirect effects of the hormone. Rat white and brown preadipocytes were therefore isolated, grown to confluence, and used to test direct effects of thyroid hormone, insulin, and glucose. Lipogenesis was assessed by tritiated water incorporation, and acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and S14 mRNAs were measured by Northern analysis. Insulin (1 nM) increased lipogenesis about 9-fold in both white and brown adipocytes. Similar increases were seen in the levels of the three mRNAs. Thyroid hormone (1 microM) stimulated lipogenesis and acetyl-CoA carboxylase, fatty acid synthase, and S14 mRNA levels up to 2-fold in both types of adipocyte in the presence or absence of insulin. A high carbohydrate level (25 mM glucose) had no effect on lipogenesis compared to a low carbohydrate level (5 mM glucose) in white and brown adipocytes. There was no synergistic effect on lipogenesis by the combination of thyroid hormone and high carbohydrate level in both types of adipocytes. These experiments have shown that T3 has small, direct stimulatory effects on lipogenesis in adipocytes. These effects are seen at a pre-translational level, through the coordinate induction of ACC, FAS, and S14 mRNAs. Although lipogenic rates were usually higher in brown adipocytes than white adipocytes, very similar patterns of regulation were seen in the two cell types. These data support the idea that the divergent results seen concerning T3 regulation of the lipogenic pathway in both brown and white adipose tissue in vivo arise from secondary effects of the alteration of thyroid status.
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PMID:Hormonal and nutritional regulation of lipogenic enzyme mRNA levels in rat primary white and brown adipocytes. 1288 95

Thyroid hormone regulates food intake. We previously reported that rats with triiodothyronine (T3)-induced thyrotoxicosis display hyperphagia associated with suppressed circulating leptin levels, increased hypothalamic neuropeptide Y (NPY) mRNA and decreased hypothalamic pro-opiomelanocortin (POMC) mRNA. AMP-activated kinase (AMPK) is a serine/threonine protein kinase that is activated when cellular energy is depleted. We hypothesized that T3 causes an increase in hypothalamic AMPK activity, which in turn contributes to the development of T3-induced hyperphagia. Rats that were given s.c. injections of T3 (4.5 nmol/kg) had increased food intake 2 h later without alterations in NPY and POMC mRNA levels, but with increased hypothalamic phosphorylated AMPK (169%) and phosphorylated acetyl-CoA carboxylase (194%). To determine the more chronic effects of T3, rats were given 6 daily s.c. injection of T3 or the vehicle. Food intake was significantly increased. Multiple T3 injections increased hypothalamic phosphorylated AMPK (278%) and phosphorylated acetyl-CoA carboxylase (335%) compared to the controls. Intracerebroventricular administration of compound C, an AMPK inhibitor, blocked the food intake induced by a single or multiple injections of T3. Taken together, these results suggest that enhanced hypothalamic AMPK phosphorylation contributes to T3-induced hyperphagia. Hypothalamic AMPK plays an important role in the regulation of food intake and body weight.
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PMID:Triiodothyronine (T3) stimulates food intake via enhanced hypothalamic AMP-activated kinase activity. 1870 95