Cellular Basis of Exercise-induced Changes in Substrate Metabolism
Finally, Neil Ruderman, MD, PhD, of the Boston University School of Medicine, a leader in the enzymology of muscle metabolic pathways, discussed the latest information on the cellular basis for exercise-induced changes in substrate metabolism.[7] Dr. Ruderman addressed the regulatory events that allow the muscle cell to utilize glucose or fatty acids at rest and during exercise, and he focused particularly on the role of AMP-activated protein kinase (AMPK) in fatty acid oxidation.
Skeletal muscles consume 80% to 90% of whole body oxygen utilized during exercise. Their choice of substrate for fuel differs during rest and exercise in normal persons. At rest (while fasting) about 90% of fuel consumption is fatty acid-derived and about 10% is carbohydrate-derived. But with moderate exercise, there are substantial increases in both fatty acid and carbohydrate oxidation. How do these shifts occur? There is an important molecular sensor that regulates the change the level of AMP in the cell, which reflects a decrease in the fuel supply.
During exercise, as a result of increased glucose uptake and glycogenolysis, glucose-6-phosphate increases in muscle cells. Normally it is not permitted to accumulate because pyruvate dehydrogenase is activated within seconds, resulting in increased flux through the Krebs cycle leading to increased glucose oxidation. Fatty acids are likewise oxidized but via a different pathway under different regulation. Lipolysis during exercise leads to increased delivery of free fatty acids to muscle cells. These are taken up by the cells, initially bound to a fatty acid binding protein, and then acted on by fatty acyl-CoA synthase to produce long chain fatty acyl-CoA.
A crucial next step is the activation of carnitine palmitoyl transferase I (CPT I) to shuttle the fatty acyl-CoA into the mitochondria for oxidation. CPT I is inhibited by malonyl-CoA, which is synthesized by the action of acetyl-CoA carboxylase (ACC), ACC is regulated positively by increased citrate (an allosteric activator that accumulates in the presence of insulin and glucose) and negatively by AMPK. Citrate activates ACC, while AMPK phosphorylates and inhibits ACC in a manner that supersedes the effect of insulin and glucose. A third regulator of malonyl-CoA is malonyl-CoA decarboxylase, the activity of which is also increased by AMPK, and which decreases malonyl-CoA levels in the cytosol.
To put these events in a physiologic context: during feeding, in the presence of insulin and glucose, malonyl-CoA accumulates and inhibits CPT I, thus inhibiting fatty acid oxidation. Conversely, when the muscle cell is deprived of glucose, or when it is contracting, malonyl-CoA decreases due to increased AMPK activity (resulting from low fuel supply and increased cellular AMP) as well as increased malonyl-CoA decarboxylase activity -- fatty acyl-CoA can then be transferred to the mitochondrion for oxidation.
So, as a result of AMPK activation during muscle contraction, the activity of ACC goes down and the activity of malonyl-CoA decarboxylase goes up, and they remain in this state for some time after the contraction. During this time the concentration of malonyl-CoA presumably remains low, permitting enhanced fatty acid oxidation. This mechanism may be a major pathway of enhancing lipid oxidation after exercise. There are also other amplifying effects of this mechanism. For instance, AMPK can also phosphorylate and inhibit glycerol phosphate acyl-transferase, an early step in forming diacylglycerol and triglycerides. It would be beneficial to prevent the accumulation of these lipid moieties in the muscle cell, inasmuch as increases in muscle diacylglycerol, triglyceride, fatty acyl-CoA, and the resultant activation of protein kinase C isoforms, are associated with insulin resistance. Furthermore, data from research by Goodyear and colleagues[8] at the Joslin Diabetes Center, Boston, show AMPK activity enhances glucose uptake into muscle cells.[8]
These data underscore the importance of effective lipid oxidation in response
taken from:http://www.medscape.com/viewarticle/419032
Correct me, then, if I am wrong...but a DCP/SesaThin/Berberine dose before workout, then HCA/Vinegar/citrate post workout would seem to be an extremely potent Recomp protocol?
Thoughts?
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