An 20-year-old male presents to the emergency room smelling quite heavily of alcohol and is unconscious. A blood test reveals severe hypoglycemic and ketoacidemia. A previous medical history states that he does not have diabetes. The metabolism of ethanol in this patient’s hepatocytes resulted in an increase of the [NADH]/[NAD+] ratio. Which of the following reaction is favored under this condition?
1.Pyruvate to acetyl-CoA
2.Citrate to isocitrate
3.Oxaloacetate to malate
4.Oxaloacetate to phosphoenolpyruvate
5.Fumarate to malate
The metabolism of ethanol consumes NAD+ by converting it to NADH, thereby increasing the ratio of [NADH]/[NAD+]. Under this condition, oxaloacetate to malate is favored.
The conversion of ethanol to acetaldehyde and acetate consumes NAD+ and produces NADH. This increases the ratio of [NADH]/[NAD+], which favors the conversion of pyruvate to lactate and other NADH consuming reactions, such as oxaloacetate to malate. Since oxaloacetate is being consumed, the TCA cycle slows down, with the excess acetyl-CoA shunted towards ketone production. The increase in malate is shunted towards fatty acid synthesis, which results in hepatocellular steatosis (fatty change) in chronic alcoholics.
Sucov and Woolard conducted a retrospective study to determine the association between alcohol intoxication and hypoglycemia in patients brought to the emergency room. They found no correlation between the glucose and ethanol concentration in patients, and patients with a high concentration of ethanol did not have an elevated risk for developing hypoglycemia. The risk of developing hypoglycemia was no different between ethanol positive and ethanol negative patients. They suggest that initial glucose testing may not be necessary for all intoxicated patients and should only be used selectively.
Ernst et al. conducted a similar retrospective study to examine the association between alcohol intoxication and hypoglycemia in the pediatric and adolescent population during an emergency room visit. Although the number of ethanol positive patients was small in this study, they found that 3.4% of these patients had hypoglycemia and altered behavior. They suggest that pediatric and adolescent patients presenting with ethanol intoxication along with altered behavior should be screened for possible hypoglycemia.