Which elevated ratio produced this patient’s hypoglycemia?
A 54-year-old alcoholic is brought to the emergency department by fire rescue after being found lying face down in the street. He is incoherent and is unable to walk in a straight line. His pulse is 110/min, his blood pressure is 135/80 mm Hg, and his respiration rate is 20/min. Physical examination reveals a diaphoretic man with generalized weakness passing in and out of consciousness. A glucose fingerstick test shows a glucose level of 45 g/dL.

NADH:NAD+

The correct answer is B. This patient is suffering from hypoglycemia related to his alcohol use. Ethanol is metabolized to acetaldehyde, which is then metabolized to acetate (acetaldehyde dehydrogenase). During both steps of ethanol metabolism, NADH is generated from NAD+. With an elevated NADH:NAD+ ratio in the liver, pyruvate is diverted to lactate, PIGwhile oxaloacetate is diverted to malate, thus inhibiting gluconeogenesis. The metabolism of ethanol is also responsible for the hepatic fatty changes seen in chronic alcoholics (increased fatty acid synthesis) Answer A is incorrect. An elevated NAD+:NADH ratio does not result from alcohol metabolism. In any event, lactate would generate pyruvate, and gluconeogenesis would not be inhibited Answer C is incorrect. An elevated NADP:NADPH results from a faulty pentose shunt. NADPH is used for fatty acid synthesis and to reduce glutathione. The above presentation and decreased gluconeogenesis are consistent with an elevated NADH/NAD+ ratio Answer D is incorrect. NADPH is produced by the pentose pathway. NADPH is used for fatty acid synthesis and to reduce glutathione. Glutathione helps prevent oxidative damage to cells by reducing hydrogen peroxide. An elevated NADPH:NADP ratio would not inhibit gluconeogenesis Answer E is incorrect. An elevated lactate: pyruvate ratio would be seen in alcohol intoxication rather than an elevated pyruvate:lactate ratio. During alcohol metabolism, the elevated NADH:NAD+ ratio leads to diversion of pyruvate to lactate.