Fatty acids metabolism, glucose phosphorylation

B. Intracellular effects include uncoupling of oxidative phosphorylation and interruption of glucose and fatty acid metabolism, which contribute to metabolic acidosis. 

Phosphorus is more readily absorbed from the intestinal tract than calcium. Approximately two-thirds of the phosphorus excreted is found in the feces, one-third in the urine. Between 10 and 20 % of phosphorus is found in tissues other than bone, and this phosphorus appears to have metabolic priority. The mechanisms which regulate deposition and release of phosphorus from bone are the same as those for calcium. Phosphorus in soft tissues plays a very vital role in many metabolic processes. The importance of adenosine triphosphate (ATP) in energy transfer systems has been discussed previously (p. 203, Chapter 16). Phosphorylation appears to be essential for the absorption of a number of nutrients, e.g., fatty acids and glucose. The phosphate radical is bound to proteins, fatty acids, carbohydrates, and enzymes. Phosphate is the chief inorganic anion of intracellular fluid, and phosphates of extracellular fluid participate in acid-base regulation. The inorganic phosphate level of blood ranges from 2 to 4 mg. per 100 ml. in adults and 3 to 5 mg. per 100 ml. in children. 

Where two enzymes compete for the same substrate, we expect to see some form of metabolic control and in this case the concentrations of NADH and acetyl-CoA are the key controlling factors (Figure 6.44). When glucose is not available as a fuel, metabolism switches to 3- oxidation of fatty acids, which generates more than sufficient quantities of both NADH and acetyl-CoA to drive the TCA cycle and to maintain oxidative phosphorylation. Pyruvate dehydrogenase activity is suppressed and pyruvate carboxylase is stimulated by ATP, NADH and acetyl-CoA (strictly speaking by low mitochondrial ratios of ADP/ATP, NAD+/NADH and coenzyme A/acetyl-CoA), so... 

By interacting with its receptors on the surface of myocytes and hepatocytes, adiponectin activates their AMPK. The activated kinase phosphorylates key metabolic enzymes (see Fig. 23-37, for example), shifting metabolism toward oxidation of fatty acids and away from lipid and glucose synthesis. 

Figure 23-2. Metabolism in the fed state. An adequate supply of carbohydrate provides glucose to replenish glycogen stores. Dietary protein provides amino acids for protein synthesis. Dietary carbohydrates, fats, and proteins can all be metabolized to generate ATP. (For clarity, ATP generation during P-oxidation of fatty acids and substrate-level phosphorylation during glycolysis is not depicted.) Excess dietary carbohydrates and amino acids are converted to fatty acids and, along with excess dietary fatty acids, stored as triacylglycerols. DHAP, dihydroxyacetone phosphate.

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