TQ1. A. What effect does the rise in cytosolic NADH seen with ethanol metabolism have on glycolysis? Hint: What coenzyme is required in glycolysis?
B. How does this relate to the fatty liver (hepatic steatosis) commonly seen in alcohol-dependent individuals? TQ2. Why might individuals with a history of gouty attacks be advised to reduce their consumption of ethanol? TQ3. Why might prothrombin time be affected in alcohol-dependent individuals? TQ4. Folate and vitamin B12 deficiencies cause a macrocytic anemia that may be seen in those with alcoholism. Why is it advisable to measure vitamin B12 levels before supplementing with folate in an individual with macrocytic anemia?
Case 1: Answers to Review Questions
RQ1.Answer = B. Phosphatidylcholine is a glycerol-based phospholipid derived from diacylglycerol phosphate (phosphatidic acid) and cytidine diphosphatecholine. Gangliosides are derived from ceramides, lipids with a sphingosine backbone. Prostaglandins of the 2 series (such as PGI2) are derived from the 20 carbon polyunsaturated fatty acid arachidonic acid. Sphingomyelin is a sphingophospholipid derived from ceramide. Vitamin D is derived from an intermediate in the biosynthetic pathway for the sterol cholesterol. RQ2.Answer = A. Statins inhibit hydroxymethylglutaryl coenzyme A (HMG CoA) reductase, thereby preventing the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of HMG CoA to mevalonate and decreasing cholesterol biosynthesis (see figure below). The decrease in cholesterol content caused by statins results in movement of the sterol regulatory element–binding protein-2 (SREBP-2) in complex with SREBP cleavage– activating protein (SCAP) from the endoplasmic reticular membrane to the Golgi membrane. SREBP-2 is cleaved, generating a transcription factor that moves to the nucleus and binds to the sterol regulatory element upstream of the genes for HMG CoA reductase and the low-density lipoprotein (LDL) receptor, increasing their expression. Humans are unable to degrade the steroid nucleus to CO2 +
H2O. Bile acid (BA) sequestrants, such as cholestyramine, prevent the absorption of bile salts by the liver, thereby increasing their excretion. The liver then takes up cholesterol via the LDL receptor and uses it to make BA, thereby reducing blood cholesterol levels. Steroid hormones are synthesized from cholesterol, and vitamin D is synthesized in skin from an intermediate (7dehydrocholesterol) in the cholesterol biosynthetic pathway. Therefore, inhibition of cholesterol synthesis would be expected to decrease their production as well.
RQ3.Answer = C. Competitive inhibitors bind to the same site as the substrate (S) and prevent the S from binding. This results in an increase in the apparent Km (Michaelis constant, or that S concentration that gives one half of the maximal velocity [Vmax]). However, because the inhibition can be reversed by adding additional substrate, the Vmax is unchanged (see figure at right). It is noncompetitive inhibitors that decrease the apparent Vmax and have no effect on Km.