Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.31 (AMP-activated protein kinase)
 13,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

AMP-activated protein kinase (AMPK) is a metabolic stress-sensing protein kinase responsible for coordinating metabolism and energy demand. In rodents, exercise accelerates fatty acid metabolism, enhances glucose uptake, and stimulates nitric oxide (NO) production in skeletal muscle. AMPK phosphorylates and inhibits acetyl-coenzyme A (CoA) carboxylase (ACC) and enhances GLUT-4 translocation. It has been reported that human skeletal muscle malonyl-CoA levels do not change in response to exercise, suggesting that other mechanisms besides inhibition of ACC may be operating to accelerate fatty acid oxidation. Here, we show that a 30-s bicycle sprint exercise increases the activity of the human skeletal muscle AMPK-alpha1 and -alpha2 isoforms approximately two- to threefold and the phosphorylation of ACC at Ser(79) (AMPK phosphorylation site) approximately 8.5-fold. Under these conditions, there is also an approximately 5.5-fold increase in phosphorylation of neuronal NO synthase-mu (nNOSmu;) at Ser(1451). These observations support the concept that inhibition of ACC is an important component in stimulating fatty acid oxidation in response to exercise and that there is coordinated regulation of nNOSmu to protect the muscle from ischemia/metabolic stress.
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PMID:AMPK signaling in contracting human skeletal muscle: acetyl-CoA carboxylase and NO synthase phosphorylation. 1105 78

The effect of prolonged moderate-intensity exercise on human skeletal muscle AMP-activated protein kinase (AMPK)alpha1 and -alpha2 activity and acetyl-CoA carboxylase (ACCbeta) and neuronal nitric oxide synthase (nNOSmu) phosphorylation was investigated. Seven active healthy individuals cycled for 30 min at a workload requiring 62.8 +/- 1.3% of peak O(2) consumption (VO(2 peak)) with muscle biopsies obtained from the vastus lateralis at rest and at 5 and 30 min of exercise. AMPKalpha1 activity was not altered by exercise; however, AMPKalpha2 activity was significantly (P < 0.05) elevated after 5 min (approximately 2-fold), and further elevated (P < 0.05) after 30 min (approximately 3-fold) of exercise. ACCbeta phosphorylation was increased (P < 0.05) after 5 min (approximately 18-fold compared with rest) and increased (P < 0.05) further after 30 min of exercise (approximately 36-fold compared with rest). Increases in AMPKalpha2 activity were significantly correlated with both increases in ACCbeta phosphorylation and reductions in muscle glycogen content. Fat oxidation tended (P = 0.058) to increase progressively during exercise. Muscle creatine phosphate was lower (P < 0.05), and muscle creatine, calculated free AMP, and free AMP-to-ATP ratio were higher (P < 0.05) at both 5 and 30 min of exercise compared with those at rest. At 30 min of exercise, the values of these metabolites were not significantly different from those at 5 min of exercise. Phosphorylation of nNOSmu was variable, and despite the mean doubling with exercise, statistically significance was not achieved (P = 0.304). Western blots indicated that AMPKapproximately 2 was associated with both nNOSmu and ACCbeta consistent with them both being substrates of AMPKalpha2 in vivo. In conclusion, AMPKalpha2 activity and ACCbeta phosphorylation increase progressively during moderate exercise at approximately 60% of VO(2 peak) in humans, with these responses more closely coupled to muscle glycogen content than muscle AMP/ATP ratio.
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PMID:Progressive increase in human skeletal muscle AMPKalpha2 activity and ACC phosphorylation during exercise. 1183 74

1. The nucleoside intermediate 5'-aminoimidazole-4-carboxyamide-ribonucleoside (AICAR) activates skeletal muscle AMP-activated protein kinase (AMPK) and increases glucose uptake. The AMPK phosphorylates neuronal nitric oxide synthase (nNOS)mu in skeletal muscle fibres. There is evidence that both AMPK and nNOSmu may be involved in the regulation of contraction-stimulated glucose uptake. 2. We examined whether both AICAR- and contraction-stimulated glucose uptake were mediated by NOS in rat skeletal muscle. 3. Rat isolated epitrochlearis muscles were subjected in vitro to electrically stimulated contractions for 10 min and/or incubated in the presence or absence of AICAR (2 mmol/L) or the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA; 100 micromol/L). 4. Muscle contraction significantly (P < 0.05) altered the metabolic profile of the muscle. In contrast, AICAR and L-NMMA had no effect on the metabolic profile of the muscle, except that AICAR increased muscle 5'-aminoimidazole-4-carboxyamide-ribonucleotide (ZMP) and AICAR content. Nitric oxide synthase inhibition caused a small but significant (P < 0.05) reduction in basal 3-O-methylglucose transport, which was observed in all treatments. 5'-Aminoimidazole-4-carboxyamide-ribonucleoside significantly increased (P < 0.05) glucose transport above basal, with NOS inhibition decreasing this slightly (increased by 209% above basal compared with 184% above basal with NOS inhibition). Contraction significantly increased glucose transport above basal, with NOS inhibition substantially reducing this (107% increase vs 31% increase). 5'-Aminoimidazole-4-carboxyamide-ribonucleoside plus contraction in combination were not additive on glucose transport. 5. These results suggest that NO plays a role in basal glucose uptake and may regulate contraction-stimulated glucose uptake. However, NOS/nitric oxide do not appear to be signalling intermediates in AICAR-stimulated skeletal muscle glucose uptake.
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PMID:5'-aminoimidazole-4-carboxyamide-ribonucleoside-activated glucose transport is not prevented by nitric oxide synthase inhibition in rat isolated skeletal muscle. 1523 27