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AMP
10%
42/403
ADP
40/403
Insulin
2%
10/403
Fructose-2,6-biphosphate
13%
52/403
Acetyl-CoA
64%
256/403
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Acetyl-CoA is an allosteric regulator of pyruvate carboxylase which acts to increase gluconeogenesis. The purpose of gluconeogenesis is to create de novo glucose to maintain blood glucose levels when glycogen stores have been exhausted. Gluconeogenesis mainly occurs in the liver where the newly manufactured glucose is used to supply red blood cells and the brain with the glucose it needs to function; whereas, the liver does not use the glucose but rather uses beta oxidation to supply itself with energy. Regulation of gluconeogenesis can be favored in one direction over the other with stimulation occurring with glucagon, acetyl CoA, and citrate; inhibition can occur when there is a high NADH/NAD+ ratio (intoxication with ethanol). Berg et al. review glycoslysis and gluconeogenesis with a focus on the first step of regulation - the interconversion of fructose-6-phosphate and fructose-1,6-phosphate controlled by phosphofructokinase (PFK) and fructose-1,6-biphosphatase. PFK is stimulated favoring glycolysis when AMP levels are high signifying a low energy state in the cell. It is inhibited when ATP and citrate are high signifying a high energy state. The opposite occurs with fructose-1,6-biphosphatase, favoring gluconeogenesis when ATP and citrate are abundant and inhibited when AMP levels are abundant. Berg et al. review the alteration of energy metabolism in the presence of ethanol. The conversion of ethanol to acetaldehyde and finally to acetate requires NAD+ converting it to NADH. This results in a high NADH/NAD+ ratio and as explained above, this inhibits gluconeogenesis. This inhibition can led to hypoglycemia when glycogen stores have been depleted. Illustration A shows a schematic of glycolysis and gluconeogenesis. Incorrect Answer: These do not increase gluconeogenesis. Answer 1 and 4: AMP and fructose-2,6-biphosphate increases glycolysis via positive feedback to phosphofructokinase 1. Answer 2: ADP stimulates the TCA cycle via positive feedback to isocitrate dehydrogenase. Answer 3: Insulin acts to stimulate glycogen synthesis via activation of glycogen synthase.
3.6
(11)
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