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Question 1. A. What is the impact of ethanol metabolism on glycolysis due to the increase in cytosolic NADH levels? Hint: Consider the required coenzyme in glycolysis.
B. How does this relate to the common occurrence of fatty liver (hepatic steatosis) in individuals dependent on alcohol?
Question 2. Why are individuals with a history of gouty attacks advised to reduce their ethanol consumption?
Question 3. How does alcohol dependency affect prothrombin time?
Question 4. Why is it recommended to measure vitamin B12 levels before supplementing with folate in individuals with macrocytic anemia caused by folate and vitamin B12 deficiencies in alcoholism?

Case 1: Review Questions Answers
Answer to Review Question 1: 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.

Answer to Review Question 2: A. Statins inhibit hydroxymethylglutaryl coenzyme A (HMG CoA) reductase, thereby preventing the NADPH-dependent reduction of HMG CoA to mevalonate and decreasing cholesterol biosynthesis. This reduction in cholesterol content caused by statins leads to the 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 translocates 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, thereby 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, leading to their increased excretion. As a result, the liver takes up cholesterol through the LDL receptor and utilizes it to produce bile acids, thereby reducing blood cholesterol levels. Steroid hormones are synthesized from cholesterol, and vitamin D is synthesized in the skin from an intermediate (7dehydrocholesterol) in the cholesterol biosynthetic pathway. Therefore, inhibiting cholesterol synthesis is expected to decrease their production as well.

Answer to Review Question 3: C. Competitive inhibitors bind to the same site as the substrate (S) and prevent the substrate from binding. This leads to an increase in the apparent Km (Michaelis constant, or the substrate concentration that gives half of the maximal velocity [Vmax]). However, since the inhibition can be reversed by adding additional substrate, the Vmax remains unchanged. It is noncompetitive inhibitors that decrease the apparent Vmax without affecting Km.

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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.