A known alcoholic is found lying semiconscious at the bottom of a stairwell with a broken arm by his landlady, who called an ambulance to take him to the emergency room. Initial laboratory studies showed are relatively large anion gap of 34 (normal = 9 to 15). His blood alcohol was elevated at 245 mg/dL (intoxication level = 150 to 300 mg/dL), and his blood glucose was 38 mg/dL (low normal). The patient/s large anion gap and hypoglycemia can best be explained by which of the following?
A. Decreased secretion of glucagon
B. Increased secretion of insulin
C. Increased urination resulting from the diuretic effect of alcohol
D. Inhibition of dehydrogenase enzymes by NADH
E. Inhibition of glycogenolysis by ethanol
Answer- D. Alcoholics frequently do not eat while binge drinking, so it is most likely that liver glycogen stores become depleted and fail to increase blood glucose levels. The resultant hypoglycemia leads to increase in the secretion of epinephrine and other hormones that mobilize fatty acids from stored triglycerides in adipose cells. These fatty acids undergo β-oxidation in the liver to provide energy. Acetyl co A, the end product of fatty acid oxidation is channeled to the pathway of ketogenesis because of the inhibition of the TCA cycle.
TCA cycle is in a suppressed state due to high levels of NADH produced by the oxidation of ethanol.
Alcohol is metabolized in two steps- i) first to acetaldehyde and ii) then to acetate. The first conversion takes place by alcohol dehydrogenase whereas the second conversion occurs under the effect of aldehyde dehydrogenase. Both these dehydrogenases require NAD+ as a coenzyme (Figure).
Figure-Metabolism of alcohol and conversion of pyruvate to lactate
Excess alcohol intake leads to accumulation of NADH that decreases gluconeogenesis as well as impairs fatty acid oxidation.( Key gluconeogenic dehydrogenases are inhibited by the elevated levels of NADH, including lactate dehydrogenase, glycerol 3-phosphate dehydrogenase, and malate dehydrogenase).
The net effect of hypoglycemia is due to an imbalance between demand and supply of glucose.
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As regards other options
Hypoglycemia is not due to decreased secretion of glucagon or increased secretion of insulin. Glycogen stores get depleted; hypoglycemia is not due to inhibition of glycogenolysis. Hypoglycemia is also not due to the diuretic effect of alcohol. All the effects are due to increased concentration of NADH.Please help Biochemistry for Medics by "CLICKING ON THE ADVERTISEMENTS" every time you visit us. Thank you!