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)

AMP-activated protein kinase (AMPK) may act as a key enzyme for metabolic adaptation to calorie restriction (CR) or reduced growth hormone (GH)-insulin-like growth factor (IGF)-1 signaling, an experimental intervention for lifespan extension in animals. We investigated the protein levels of AMPKalpha and a downstream enzyme, acetyl-CoA carboxylase (ACC), by immunoblotting of liver and quadriceps femoris muscle (QFM) extracts from 6-month-old wild-type (W) and GH-suppressed transgenic (Tg) Wistar rats fed ad libitum (AL) or 30% CR diets from 6weeks of age. A modified alternate-day feeding regimen for CR yielded a fed-fasted cycle in CR rats, and therefore the effects of overnight fasting in W-AL rats were also evaluated. CR decreased threonine-172-phosphorylated AMPKalpha (p-AMPKalpha; an activated form) levels in the liver, whereas the CR-fed-fasted cycle or overnight fasting did not significantly affect the p-AMPKalpha level. In the QFM, the p-AMPKalpha level was slightly elevated in the CR-fasted phase, but greatly increased in the AL-fasted phase. Suppression of GH did not affect the p-AMPKalpha level. The phosphorylated-ACC levels did not alter in parallel with the p-AMPKalpha level, particularly in the liver. The present results suggest that CR down-regulates the AMPK activity in the liver on a long-term basis.
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PMID:Down-regulation of AMP-activated protein kinase by calorie restriction in rat liver. 1770 21

Inactivity is known to induce muscle atrophy, which is associated with insulin and insulin-like growth factor-1 (IGF-1) resistance, but the associated mechanisms remain poorly defined. The hindlimb unloading model has been used to reduce muscle activity. The objective of this study was to show the effect of hindlimb unloading on IGF-1 signaling and AMP-activated protein kinase (AMPK) activity in rat soleus and extensor digitorum longus (EDL) muscles. Twelve 7-week-old male Sprague-Dawley rats were assigned to 2 treatments: (i) rats without hindlimb unloading (Con) and (ii) rats with hindlimb unloading (Unload). After 2 weeks of treatment, the soleus and EDL muscles were dissected and used for biochemical analyses. Hindlimb unloading induced severe muscle atrophy in soleus muscle (0.122+/-0.007 g for Con vs. 0.031+/-0.004 g for Unload, p<0.01), but only slight atrophy in EDL muscle. The phosphorylation of AMPK (p<0.05) and its downstream substrate, acetyl-CoA carboxylase (ACC) (p<0.01) were reduced in soleus muscle due to unloading. The concentration of insulin receptor substrate-1 (IRS-1) and phosphorylation of IRS-1 at Ser636-639 and Ser789 were also reduced. Downstream IGF-1 signaling was downregulated in Unload rats. A reduction in IGF-1 concentration in unloaded soleus muscle was also observed. A slight reduction in AMPK activity and IGF-1 signaling were observed in EDL muscle. Since AMPK controls the sensitivity of IGF-1 signaling through phosphorylation at Ser789, the reduction in AMPK activity is expected to reduce the response of downstream IGF-1 signaling to IGF-1; this, in combination with reduced IGF-1 concentration, might be responsible for the severe muscle atrophy observed in unloaded soleus muscle.
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PMID:Rat hindlimb unloading down-regulates insulin like growth factor-1 signaling and AMP-activated protein kinase, and leads to severe atrophy of the soleus muscle. 1805 85

The influence of adenosine mono phosphate (AMP)-activated protein kinase (AMPK) vs Akt-mammalian target of rapamycin C1 (mTORC1) protein signaling mechanisms on converting differentiated exercise into training specific adaptations is not well-established. To investigate this, human subjects were divided into endurance, strength, and non-exercise control groups. Data were obtained before and during post-exercise recovery from single-bout exercise, conducted with an exercise mode to which the exercise subjects were accustomed through 10 weeks of prior training. Blood and muscle samples were analyzed for plasma substrates and hormones and for muscle markers of AMPK and Akt-mTORC1 protein signaling. Increases in plasma glucose, insulin, growth hormone (GH), and insulin-like growth factor (IGF)-1, and in phosphorylated muscle phospho-Akt substrate (PAS) of 160 kDa, mTOR, 70 kDa ribosomal protein S6 kinase, eukaryotic initiation factor 4E, and glycogen synthase kinase 3a were observed after strength exercise. Increased phosphorylation of AMPK, histone deacetylase5 (HDAC5), cAMP response element-binding protein, and acetyl-CoA carboxylase (ACC) was observed after endurance exercise, but not differently from after strength exercise. No changes in protein phosphorylation were observed in non-exercise controls. Endurance training produced an increase in maximal oxygen uptake and a decrease in submaximal exercise heart rate, while strength training produced increases in muscle cross-sectional area and strength. No changes in basal levels of signaling proteins were observed in response to training. The results support that in training-accustomed individuals, mTORC1 signaling is preferentially activated after hypertrophy-inducing exercise, while AMPK signaling is less specific for differentiated exercise.
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PMID:Differentiated mTOR but not AMPK signaling after strength vs endurance exercise in training-accustomed individuals. 2380 89