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)

Leptin, a circulating hormone secreted mainly from adipose tissues, is involved in the control of body weight. The plasma concentrations are correlated with body mass index, and are reported to be high in patients with insulin resistance, which is one of the major risk factors for cardiovascular disease. However, the direct effect of leptin on vascular wall cells is not fully understood. In this study, we investigated the effects of leptin on reactive oxygen species (ROS) generation and expression of monocyte chemoattractant protein-1 (MCP-1) in bovine aortic endothelial cells (BAEC). We found that leptin increases ROS generation in BAEC in a dose-dependent manner and that its effects are additive with those of glucose. Rotenone, thenoyltrifluoroacetone (TTFA), carbonyl cyanide m-chlorophenylhydrazone (CCCP), Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), uncoupling protein-1 (UCP1) HVJ-liposomes, or manganese superoxide dismutase (MnSOD) HVJ-liposomes completely prevented the effect of leptin, suggesting that ROS arise from mitochondrial electron transport. Leptin increased fatty acid oxidation by stimulating the activity of carnitine palmitoyltransferase-1 (CPT-1) and inhibiting that of acetyl-CoA carboxylase (ACC), pace-setting enzymes for fatty acid oxidation and synthesis, respectively. Leptin-induced ROS generation, CPT-1 activation, ACC inhibition, and MCP-1 overproduction were found to be completely prevented by either genistein, a tyrosine kinase inhibitor, H-89, a protein kinase A (PKA) inhibitor, or tetradecylglycidate, a CPT-1 inhibitor. Leptin activated PKA, and the effects of leptin were inhibited by the cAMP antagonist Rp-cAMPS. These results suggest that leptin induces ROS generation by increasing fatty acid oxidation via PKA activation, which may play an important role in the progression of atherosclerosis in insulin-resistant obese diabetic patients.
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PMID:Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase A. 1134 29

The membrane-associated human isozyme of carbonic anhydrase, hCA IV, has been investigated for its interaction with anion inhibitors, for the CO(2) hydration reaction catalyzed by this enzyme. Surprisingly, halides were observed to act as potent hCA IV inhibitors, with inhibition constants in the range of 70-90 microM, although most of these ions, and especially fluoride, the best hCA IV inhibitor among the halides, are weak inhibitors of other isozymes, such as hCA I, II and V. The metal poisons cyanate, cyanide and hydrogen sulfide were weaker hCA IV inhibitors (K(i)'s in the range of 0.6-3.9 mM), whereas thiocyanate, azide, nitrate and nitrite showed even weaker inhibitory properties (K(i)'s in the range of 30.8-65.1 mM). Sulfate was a good hCA IV inhibitor (K(i) of 9 mM), although it is a much weaker inhibitor of isozymes I, II, V and IX. Excellent hCA IV inhibitory properties showed sulfamic acid, sulfamide, phenylboronic acid and phenylarsonic acid, with K(i)'s in the range of 0.87-0.93 microM, whereas their affinities for the other investigated isozymes were in the millimolar range. The interaction of some anions with the mitochondrial isozyme hCA V has also been investigated for the first time here. It has been observed that among all these isozymes, hCA V has the lowest affinity for bicarbonate and carbonate (K(i)'s in the range of 82-95 mM), which may represent an evolutionary adaptation of this isozyme to the rather alkaline environment (pH 8.5) within the mitochondria, where hCA V plays important functions in some biosynthetic reactions involving carboxylating enzymes (pyruvate carboxylase and acetyl coenzyme A carboxylase). There are important differences of affinity for anions between the two membrane-associated isozymes, hCA IV and hCA IX.
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PMID:Carbonic anhydrase inhibitors: inhibition of the membrane-bound human isozyme IV with anions. 1550 Oct 38