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)

Antiobesity drugs that target peripheral metabolism may avoid some of the problems that have been encountered with centrally acting anorectic drugs. Moreover, if they cause weight loss by increasing fat oxidation, they not only address a cause of obesity but also should promote loss of fat rather than lean tissue and improve insulin sensitivity. Weight loss may be slow but more sustained than with anorectic drugs, and thermogenesis may be insufficient to cause any discomfort. Some thermogenic approaches are the activation of adrenergic, thyroid hormone or growth hormone receptors and the inhibition of glucocorticoid receptors; the modulation of transcription factors [e.g. peroxisome proliferator-activated receptor delta (PPARdelta) activators] or enzymes [e.g. glutamine fructose-6-phosphate amidotransferase (GFAT) inhibitors] that promote mitochondrial biogenesis, and the modulation of transcription factors (PPAR alpha activators) or enzymes (AMP-activated protein kinase) that promote fatty acid oxidation. More surprisingly, studies on genetically modified animals and with enzyme inhibitors suggest that inhibitors of fatty acid synthesis [e.g. ATP citrate lyase, fatty acid synthase, acetyl-CoA carboxylase (ACC)], fatty acid interconversion [stearoyl-CoA desaturase (SCD)] and triglyceride synthesis (e.g. acyl-CoA : diacylglycerol acyltransferase) may all be thermogenic. Some targets have been validated only by deleting genes in the whole animal. In these cases, it is possible that deletion of the protein in the brain is responsible for the effect on adiposity, and therefore a centrally penetrant drug would be required. Moreover, whilst a genetically modified mouse may display resistance to obesity in response to a high fat diet, it requires a tool compound to demonstrate that a drug might actually cause weight loss. Even then, it is possible that differences between rodents and humans, such as the greater thermogenic capacity of rodents, may give a misleading impression of the potential of a drug.
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PMID:Thermogenic and metabolic antiobesity drugs: rationale and opportunities. 1739 Nov 51

Spirotetramat (STM), an active ingredient of insecticide Movento 100 suspension concentrate (M100), is an inhibitor of acetyl-CoA carboxylase (ACC). The ACC is catalyst of acetyl-CoA to malonyl-CoA (MCA) reaction. MCA is the rate limiting steps of fatty acid biosynthesis. An 18-years-old man, who was referred to our ward from a local hospital, ingested 100 ml of M100, 18 h before. When we visited him, he was confused with stable vital signs and complained of vomiting and epigastric discomfort. He experienced hypoglycemia (blood sugar = 31 mg/dl) that was treated by hypertonic 20% dextrose serum and continued by maintenance DW10% (100 ml/h) up to 3 h. The first electrocardiogram showed ST-elevation. The results of urgent bedside echocardiography findings were normal. His first troponin I value was 0.01 ng/ml and at 1 and 6 h later were zero. The elevated ST segment gradually returned to baseline through next 6 h. STM ingestion can cause hypoglycemia and ST changes.
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PMID:Hypoglycemia and revisable ST-elevation induced by Movento. 2785 99