Genetics Gem: Acetaldehyde, the product of ethanol oxidation by the hepatic, cytosolic, nicotinamide adenine dinucleotide (NAD+)-requiring enzyme alcohol dehydrogenase (ADH), is oxidized to acetate by the mitochondrial, NAD+-requiring aldehyde dehydrogenase (ALDH2). The majority of individuals of East Asian (but not European or African) heritage have a single nucleotide polymorphism (SNP) that renders ALDH2 essentially inactive. This results in aldehyde-induced facial flushing and mild to moderate intoxication after consumption of small amounts of ethanol.
Review Questions: Choose the ONE best answer.
RQ1. Many of the metabolic consequences of chronic excessive alcohol consumption seen in AK are the result of an increase in the ratio of reduced nicotinamide adenine dinucleotide (NADH) to its oxidized form (NAD+) in both the cytoplasm and mitochondria. Which of the following statements concerning the effects of the rise in mitochondrial NADH is correct?
A. Fatty acid oxidation is increased.
B. Gluconeogenesis is increased.
C. Lipolysis is inhibited.
D. The tricarboxylic acid cycle is inhibited.
E. The reduction of malate to oxaloacetate in the malate–aspartate shuttle is increased.
RQ2. Ethanol can also be oxidized by cytochrome P450 (CYP) enzymes, and CYP2E1 is an important example. CYP2E1, which is ethanol inducible, generates reactive oxygen species (ROS) in its metabolism of ethanol.
Which of the following statements concerning the CYP proteins is correct?
A. CYP proteins are heme-containing dioxygenases.
B. CYP proteins of the inner mitochondrial membrane are involved in detoxification reactions.
C. CYP proteins of the smooth endoplasmic reticular membrane are involved in the synthesis of steroid hormones, bile acids, and calcitriol.
D. ROS such as hydrogen peroxide generated by CYP2E1 can be oxidized by glutathione peroxidase.
E. The pentose phosphate pathway is an important source of the nicotinamide adenine dinucleotide phosphate (NADPH) that provides the reducing equivalents needed for activity of CYP proteins and the regeneration of functional glutathione.
RQ3. Alcohol is known to modulate the levels of serotonin in the central nervous system, where the monoamine functions as a neurotransmitter. Which of the following statements about serotonin is correct? Serotonin is:
A. associated with anxiety and depression.
B. degraded via methylation by monoamine oxidase, which also degrades the catecholamines.
C. released by activated platelets.
D. synthesized from tyrosine in a two-step process that utilizes a tetrahydrobiopterin-requiring hydroxylase and a pyridoxal phosphate– requiring carboxylase.
RQ4. Chronic, excessive consumption of alcohol is a leading cause of acute pancreatitis, a painful inflammatory condition that results from autodigestion of the gland by premature activation of pancreatic enzymes. Which of the following statements concerning the pancreas is correct?
A. Autodigestion of the pancreas would be expected to result in a decrease in pancreatic proteins in the blood.
B. In individuals who progress from acute to chronic pancreatitis, with the characteristic structural changes that result in decreased pancreatic function, diabetes and steatorrhea are expected findings.
C. In response to secretin, the exocrine pancreas secretes protons to lower the pH in the intestinal lumen.
D. Pancreatitis may also be seen in individuals with hypercholesterolemia.