Chapter 7 - Lipid and Ethanol Metabolism Flashcards
A deficiency of pancreatic exocrine secretion can result in which one of the following?
(A) An increased pH in the intestinal lumen
(B) An increased absorption of fat-soluble vitamins
(C) A decreased formation of bile salt micelles
(D) Increased levels of blood chylomicrons
(E) Decreased amounts of fat in the stool
The answer is C. The pancreas produces bicarbonate (which neutralizes stomach acid) and digestive enzymes (including pancreatic lipase and colipase, enzymes that degrade dietary lipids). The decreased production of bicarbonate will lead to a decrease of intestinal pH. Lower levels of pancreatic lipase will result in the decreased digestion of dietary triacylglyc- erols, which will lead to the formation of fewer bile salt micelles. The reduced pH will also interfere with the ability of the bile salts to effectively form micelles. Intestinal cells will have less substrate for chylomicron formation, and less fat-soluble vitamins will be absorbed. More dietary fat will be excreted in the feces.
Choose the one best answer that most accurately describes some properties of acetyl-CoA carboxylase.
Required cofactor / Intracellular location / Allosteric modifier / Enzyme that catalyzes a covalent modification
(A) Biotin / Mitochondrial / Citrate / PKA
(B) Biotin / Cytoplasmic / Citrate / AMP-activated protein kinase
(C) Thiamine / Mitochondrial / Acetyl-CoA / PKA
(D) Thiamine / Cytoplasmic / Acetyl-CoA / AMP-activated protein kinase
(E) None / Mitochondrial / Malonyl-CoA/ PKA
(F) None / Cytoplasmic / Malonyl-CoA / AMP-activated protein kinase
The answer is B. Biotin is required for the acetyl-CoA carboxylase reaction in which the sub- strate, acetyl-CoA, is carboxylated by the addition of CO2 to form malonyl-CoA. This reaction occurs in the cytosol. Malonyl-CoA provides the 2-carbon units that add to the growing fatty acid chain on the fatty acid synthase complex. As the growing chain is elongated, malonyl-CoA is decarboxylated. Citrate is an allosteric activator of the enzyme, and the enzyme is inhibited by phosphorylation by the AMP-activated protein kinase.
The synthesis of fatty acids from glucose in the liver is best described by which one of the following?
(A) The pathway occurs solely in the mitochondria.
(B) It requires a covalently bound derivative of pantothenic acid.
(C) It requires NADPH derived solely from the pentose phosphate pathway.
(D) The pathway is primarily regulated by isocitrate.
(E) The pathway does not utilize a carboxylation reaction.
The answer is B. The synthesis of fatty acids from glucose occurs in the cytosol, except for the mitochondrial reactions in which pyruvate is converted to citrate (pyruvate to oxaloacetate, pyruvate to acetyl-CoA, and oxaloacetate and acetyl-CoA condense to form citrate). Biotin
is required for the conversion of pyruvate to oxaloacetate (a carboxylation reaction), which combines with acetyl-CoA to form citrate. Biotin is also required by acetyl-CoA carboxylase. Citrate, not isocitrate, is a key regulatory compound for acetyl-CoA carboxylase. Pantothenic acid is covalently bound to the fatty acid synthase complex as part of a phosphopantetheinyl residue. During the reduction reactions on the synthase complex, the growing fatty acid chain is attached to this residue. NADPH, produced by the malic enzyme as well as by the pentose phosphate pathway, provides the reducing equivalents.
Which one of the following best describes the synthesis of triglyceride in adipose tissue?
Source of fatty acids / Source of backbone / Requires coenzyme A / Requires lipoprotein lipase / Requires 2-monoacylglycerol
(A) VLDL / Glycerol / Yes / No / Yes
(B) Chylomicrons / Glycerol / No / Yes / No
(C) VLDL and chylomicrons / DHAP / Yes / No / Yes
(D) VLDL and chylomicrons / DHAP / Yes / No / No
(E) Chylomicrons / DHAP / No / Yes / Yes
(F) VLDL / Glycerol / No / Yes / No
The answer is D. Fatty acids, cleaved from the triacylglycerols of chylomicrons and VLDL by the action of lipoprotein lipase, are taken up by adipose cells and react with coenzyme A to form fatty acyl-CoA. The lipoprotein lipase is not required to synthesize triglyceride within the adipocyte. Glucose is converted via DHAP to glycerol-3-phosphate, which reacts with fatty acyl-CoA to form phosphatidic acid. Adipose tissue lacks glycerol kinase and cannot use glycerol to directly form glycerol-3-phosphate. After inorganic phosphate is released from phosphatidic acid, the resultant diacylglycerol reacts with another fatty acyl-CoA
to form a triacylglycerol, which is stored in the adipose cells. (2-Monoacylglycerol is an intermediate for triglyceride synthesis only in intestinal cells, and is not produced in the adipocyte.)
Which one of the following sequences places the lipoproteins in the order of most dense to
least dense?
(A) HDL/VLDL/chylomicrons/LDL (B) HDL/LDL/VLDL/chylomicrons (C) LDL/chylomicrons/HDL/VLDL (D) VLDL/chylomicrons/LDL/HDL (E) LDL/chylomicrons/VLDL/HDL
The answer is B. Because chylomicrons contain the most triacylglycerol, they are the least dense of the blood lipoproteins. Because VLDL contains more protein than chylomicrons, it is more dense than chylomicrons, but less dense than LDL. Because LDL is produced by the degradation of the triacylglycerols of VLDL, LDL is denser than VLDL. HDL is the most dense of the blood lipoproteins. It has the most protein and the least triacylglycerol (see Tables 7.2 and 7.3).
Which one of the following best represents fasting conditions?
Activity of hormone-sensitive lipase / Fate of glycerol / VLDL production / Modification of acetyl-CoA carboxylase / Ketone body production
(A) Inactive / Glycolysis / High / Dephosphorylated / No
(B) Active / Glycolysis / High / Phosphorylated / Yes
(C) Inactive / Glycolysis / High / Dephosphorylated/ No
(D) Active / Gluconeogenesis / Low / Phosphorylated / No
(E) Inactive / Gluconeogenesis / Low / Dephosphorylated / Yes
(F) Active / Gluconeogenesis / Low / Phosphorylated / Yes
The answer is F. During fasting, the hormone-sensitive lipase of adipose tissue is activated
by a mechanism involving increased glucagon (and decreased insulin), cAMP, and protein kinase A. Phosphorylation of hormone-sensitive lipase activates the enzyme. Triacylglycerols are degraded, and fatty acids and glycerol are released into the blood. In the liver, glycerol is converted to glucose by gluconeogenesis and fatty acids are oxidized to produce ketone bodies. These fuels are released into the blood and supply energy to various tissues. During fasting, the liver does not produce significant quantities of VLDL. Fatty acid synthesis is reduced owing to the phosphorylation and inactivation of acetyl-CoA carboxylase by the AMP-activated protein kinase.
A molecule of palmitic acid, attached to carbon 1 of the glycerol moiety of a triacylglycerol, is ingested and digested. It passes into the blood, is stored in a fat cell, and ultimately is oxidized to CO2 and H2O in a muscle cell. Choose the molecular complex in the blood in which the palmitate residue is carried from the first site to the second in each of the four questions that follow. An answer may be used once, more than once, or not at all.
From the lumen of the gut to the surface of the gut epithelial cell (A) VLDL (B) Chylomicron (C) Fatty acid–albumin complex (D) Bile salt micelle (E) LDL
The answer is D. A palmitate residue attached to carbon 1 of a dietary triacylglycerol is released by pancreatic lipase and carried from the intestinal lumen to the gut epithelial cell in a bile salt micelle, which will allow absorption of the fatty acid by the intestinal epithelial cell.
A molecule of palmitic acid, attached to carbon 1 of the glycerol moiety of a triacylglycerol, is ingested and digested. It passes into the blood, is stored in a fat cell, and ultimately is oxidized to CO2 and H2O in a muscle cell. Choose the molecular complex in the blood in which the palmitate residue is carried from the first site to the second in each of the four questions that follow. An answer may be used once, more than once, or not at all.
From the gut epithelial cell to the blood (A) VLDL (B) Chylomicron (C) Fatty acid–albumin complex (D) Bile salt micelle (E) LDL
The answer is B. Palmitate is absorbed into the intestinal cell and utilized to synthesize a triacylglycerol, which is packaged in a nascent chylomicron and secreted via the lymph into the blood.
A molecule of palmitic acid, attached to carbon 1 of the glycerol moiety of a triacylglycerol, is ingested and digested. It passes into the blood, is stored in a fat cell, and ultimately is oxidized to CO2 and H2O in a muscle cell. Choose the molecular complex in the blood in which the palmitate residue is carried from the first site to the second in each of the four questions that follow. An answer may be used once, more than once, or not at all.
From the intestine through the blood to a fat cell (A) VLDL (B) Chylomicron (C) Fatty acid–albumin complex (D) Bile salt micelle (E) LDL
The answer is B. The chylomicron, containing the palmitate, matures in the blood by accept- ing proteins from HDL. It travels to a fat cell. VLDL is the particle made in the liver with endogenous triglyceride.
A molecule of palmitic acid, attached to carbon 1 of the glycerol moiety of a triacylglycerol, is ingested and digested. It passes into the blood, is stored in a fat cell, and ultimately is oxidized to CO2 and H2O in a muscle cell. Choose the molecular complex in the blood in which the palmitate residue is carried from the first site to the second in each of the four questions that follow. An answer may be used once, more than once, or not at all.
From a fat cell to a muscle cell (A) VLDL (B) Chylomicron (C) Fatty acid–albumin complex (D) Bile salt micelle (E) LDL
The answer is C. The chylomicron triacylglycerol is digested by lipoprotein lipase, and the palmitate enters a fat cell and is stored as triacylglycerol. It is released as free palmitate and carried, complexed with albumin, to a muscle cell, where it is oxidized.
A 6-month-old baby was doing well until he developed viral gastroenteritis and was unable to tolerate oral feeding for 2 days. He is admitted to the hospital with encephalopathy, cardiomegally and heart failure, poor muscle tone, and hypoketotic hypoglycemia. Blood work did not detect any medium-chain dicarboxylic acids.
Once this baby is diagnosed and treated, his diet will need to be very restricted. Theoretically, which one of the following fatty acids will he be able to consume and metabolize?
(A) An 8-carbon fatty acid
(B) A 14-carbon fatty acid
(C) A 20-carbon fatty acid
(D) Only unsaturated fatty acids, regardless of
chain length
(E) Only saturated fatty acids, regardless of
chain length
The answer is A. This baby has primary carnitine deficiency, an autosomal recessive disorder. The lack of medium-chain dicarboxylic acids in the blood rules out an MCAD deficiency. He is unable to transport blood-borne carnitine into the muscle and liver, thereby blocking fatty acid oxidation in those tissues. Carnitine is required to transfer most fatty acids from the cytoplasm to the matrix of the mitochondria. However, short- and medium-chain fatty acids (up to 10 or 12 carbons) are sufficiently water-soluble such that they can enter cells and be transferred into the mitochondria in the absence of carnitine. Once inside the mitochondria, an acyl-CoA synthetase will activate the fatty acid to an acyl-CoA such that β-oxidation can occur. The transfer is not affected whether the fatty acid is saturated or unsaturated; the chain length is the determining factor. Dietary restriction of long-chain fatty acids is essential to treat this disorder and alleviate the symptoms. The patient was doing well while feeding on a regular schedule because of the carbohydrate in the diet. Once the child had an extended fast, and needed to oxidize fatty acids for energy, the symptoms of carnitine deficiency became apparent. The hypoketotic hypoglycemia is a strong indication that the problem is in fatty acid oxidation.
A 6-month-old baby was doing well until he developed viral gastroenteritis and was unable to tolerate oral feeding for 2 days. He is admitted to the hospital with encephalopathy, cardiomegally and heart failure, poor muscle tone, and hypoketotic hypoglycemia. Blood work did not detect any medium-chain dicarboxylic acids.
Which one of the following foods or supplements would be allowable on the above patient’s restricted diet? (A) Coconut oil (B) Tuna (C) Walnuts (D) Spinach (E) Oleic acid supplements
The answer is A. The patient has a primary carnitine deficiency and can only metabolize medium-chain fatty acids. Coconut oil is high in medium-chain saturated fatty acids. Tuna and certain nuts are high in very long-chain fatty acids and omega-3 fatty acids. Spinach is a good source of ALA (alpha-linolenic acid), and omega-6 fatty acids. Oleic acid is a cis-Δ9 C18:1 fatty acid, and would not be metabolized in a child lacking carnitine in the cells.
A 6-month-old baby was doing well until he developed viral gastroenteritis and was unable to tolerate oral feeding for 2 days. He is admitted to the hospital with encephalopathy, cardiomegally and heart failure, poor muscle tone, and hypoketotic hypoglycemia. Blood work did not detect any medium-chain dicarboxylic acids.
Dietary supplementation of which one of the following would be beneficial to this patient? (A) Pantothenic acid (B) Niacin (C) Riboflavin (D) Carnitine (E) Thiamine
The answer is D. In many cases of primary carnitine deficiency, increasing the blood levels of carnitine is sufficient to allow some transport of carnitine into cells such that fatty acid oxida- tion can occur. While pantothenic acid (part of coenzyme A), niacin (the precursor for NAD1), and riboflavin (needed for FAD) are required for fatty acid oxidation, the rate-limiting step in these patients is the transport of the fatty acids from the cellular cytoplasm to the matrix of the mitochondria.
A 50-year-old male patient has high cholesterol levels and is placed on lovastatin. He is counseled to stop drinking his usual glass of grapefruit juice every morning.
Which of the following may occur when someone taking lovastatin chronically consumes grapefruit juice? (A) Cholesterol levels increase (B) Muscle pain and discomfort (C) Steatorrhea (D) Acid reflux (E) A decrease in HDL levels
The answer is B. Grapefruit juice contains furanocoumarins, which inhibit the cytochrome P450 complex CYP3A4. This complex modifies various statins for rapid excretion from the body. Thus, in the presence of grapefruit juice, statin levels will be higher than expected. This will lead to prolonged inhibition of HMG-CoA reductase and a reduction of cholesterol levels (with minimal effect on HDL levels), but will also increase the probability of side effects from statin treatment, one of which is muscle pain and weakness. The grapefruit juice plus statin will not lead to gastric reflux or steatorrhea.
A 50-year-old male patient has high cholesterol levels and is placed on lovastatin. He is counseled to stop drinking his usual glass of grapefruit juice every morning.
Given that grapefruit juice interferes with lovastatin action, which one of the following best explains this interaction?
(A) Grapefruit juice inhibits the cytochrome p450 enzyme which modifies lovastatin for excretion.
(B) Grapefruit juice stimulates the cytochrome p450 enzyme which modifies lovastatin for excretion.
(C) Grapefruit juice is a competitive inhibitor of lovastatin binding to cholesterol.
(D) Grapefruit juice is a competitive inhibitor of HMG-CoA reductase.
(E) Grapefruit juice reduces the maximal velocity of HMG-CoA reductase.
The answer is A. Grapefruit juice contains furanocoumarins, which inhibit the cytochrome P450 enzyme CYP3A4 that prepares statins for excretion. Grapefruit juice does not act as an inhibitor of HMG-CoA reductase. Lovastatin binds to HMG-CoA reductase, but not to
cholesterol.
Aspirin is used in small daily doses to help prevent heart attacks and/or strokes. Aspirin can be used in this fashion because it inhibits which one of the following? (A) Prostaglandin synthesis (B) Thromboxane synthesis (C) Arachidonic acid synthesis (D) Leukotriene synthesis (E) Linolenic acid synthesis
The answer is B. Thromboxanes promote platelet aggregation, and aspirin blocks this function through reducing the synthesis of thromboxanes. This decreases the chances of a clot forming in a coronary artery (MI) or in the artery that feeds the brain (CVA). Aspirin also inhibits prostaglandin synthesis, but this is an anti-inflammatory property. Leukotrienes are involved in allergies and asthma, and their synthesis requires lipoxygenase, which is not inhibited by aspirin. Arachidonic acid is derived from linoleic acid, and that synthesis (fatty acid elongation) is not inhibited by aspirin. Linolenic acid is an essential fatty acid, and cannot be synthesized by humans.
A patient with a hyperlipoproteinemia would most likely benefit from a low- carbohydrate diet if the lipoproteins that are elevated in the blood belong to which class of lipoproteins? Choose the one best answer. (A) Chylomicrons (B) VLDL (C) LDL (D) HDL (E) Chylomicrons and VLDL (F) VLDL and LDL (G) LDL and HDL
The answer is B. VLDL is produced mainly from dietary carbohydrate, LDL is produced from VLDL, and chylomicrons contain primarily dietary triacylglycerol. Elevated HDL levels are desirable and are not considered to be a lipid disorder. HDL also contains low levels of triglyceride. A low-carbohydrate diet would be expected to reduce the level of circulating VLDL due to reduced fatty acid and triglyceride synthesis in the liver.
An individual has been determined to have hypertriglyceridemia, with a triglyceride level of 350 mg/dL (normal is <150 mg/dL). The patient decides to reduce this level by keeping his caloric intake the same, but switching to a low-fat, low-protein, high-carbohydrate diet. Three months later, after sticking faithfully to his diet, his triglyceride level was 375 mg/dL. This increase in lipid content is being caused by which component of his new diet? (A) Phospholipids (B) Triglycerides (C) Amino acids (D) Carbohydrates (E) Cholesterol
The answer is D. Dietary glucose is the major source of carbon for synthesizing fatty acids in humans. In a high-carbohydrate diet, excess carbohydrates are converted to fat (fatty acids and glycerol) in the liver, packaged as VLDL, and sent into the circulation for storage in the fat cells. The new diet has reduced dietary lipids, which lower chylomicron levels, but the excess carbohydrate in the diet is leading to increased VLDL synthesis and elevated triglyceride levels. Dietary amino acids are usually incorporated into proteins, particularly in a low-protein diet.
An alcoholic who went on a weekend binge without eating any food was found to have severe hypoglycemia. Hypoglycemia occurred because the metabolism of ethanol prevented the production of blood glucose from which one of the following? Choose the one best answer. (A) Glycogen (B) Lactate (C) Glycerol (D) Oxaloacetate (E) Lactate, glycerol, and oxaloacetate
The answer is E. Ethanol metabolism (which produces high NADH levels) does not prevent glycogen degradation. In fact, glycogen stores would be rapidly depleted under these conditions because of decreased gluconeogenesis. Lactate is converted to pyruvate during gluconeogenesis. The pyruvate–lactate equilibrium greatly favors lactate when NADH is high. Thus, alanine and lactate are prevented from producing glucose. Lactate levels are elevated, and
a lactic acidosis can result. Glycerol normally enters gluconeogenesis by forming glycerol- 3-phosphate, which is oxidized to DHAP. High NADH levels prevent this oxidation. Aspartic acid is converted to oxaloacetate (via transamination), as do other amino acid degradation products that enter the TCA cycle (α-ketoglutarate, succinyl-CoA, fumarate). However, the high NADH levels favor malate formation from oxaloacetate, reducing the amount of oxaloacetate available for gluconeogenesis (through the phosphoenolpyruvate carboxykinase reaction). Thus, the three major gluconeogenic precursors (alanine, glycerol, and lactate) do not form glucose because of the high NADH levels, and as glycogen stores are depleted, hypoglycemia results.
A man has just received his fourth DUI citation. The judge orders an alcohol dependency program complete with a medication that makes him have nausea and vomiting if he drinks alcohol while taking the medication. The drug-induced illness is due to the buildup of which one of the following? (A) Ethanol (B) Acetaldehyde (C) Acetate (D) Acetyl-CoA (E) Acetyl phosphate
The answer is B. The court-ordered medication is disulfiram. Disulfiram inhibits aldehyde dehydrogenase, which greatly reduces the amount of acetaldehyde that is converted to acetate. This causes an accumulation of acetaldehyde, which is the substance responsible for the symptoms of a “hangover,” including nausea and vomiting. Alcohol dehydrogenase reduces ethanol to acetaldehyde. Acetyl-CoA synthetase converts acetate to acetyl-CoA.
A 52-year-old man, after suffering a heart attack, was put on 81 mg of aspirin daily by his cardiologist. The purpose of this treatment is to reduce the levels of which one of the following? (A) Cytokines (B) Leukotrienes (C) Thromboxanes (D) Cholesterol (E) Triglycerides
The answer is C. Platelet aggregation is often a determining factor in heart attacks. Thromboxane A2, produced by platelets, promotes platelet aggregation when clotting is required, and inhibition of thromboxane A2 synthesis by aspirin reduces the potential for inappropriate clot formation, and further heart attacks. Thromboxane A2 is produced from arachidonic acid by the action of cyclooxygenase, the enzyme covalently modified and irreversibly inhibited by aspirin. Leukotrienes are also synthesized from arachidonic acid, but utilize lipoxygenase in their synthesis, which is not inhibited by aspirin. Cholesterol, triglyceride, and cytokine synthesis do not require cyclooxygenase activity.
Remembering the distribution and solubility of ethanol, after several drinks with an
evening meal, in which of the following tissues would you find the LEAST amount of alcohol?
(A) Brain
(B) Liver
(C) Fatty tissue
(D) Central cornea
The answer is D. Ethanol is both water- and lipid-soluble. It is easily absorbed from the gastrointestinal tract and is distributed throughout the body via the blood stream. It is mostly metabolized in the liver, so the level would be high in this tissue. It is lipid-soluble, so it would be found in fatty tissue. It has many central effects in the brain, so it easily passes the blood– brain barrier. The central cornea has no arterial supply. The only way alcohol could accumulate in the central cornea would be through diffusion into the aqueous humor and then into the central cornea, a slower and less-efficient system. Therefore, the tissue with the lowest level of alcohol would be the central cornea.
A 14-year-old girl with Type 1 diabetes has had viral gastroenteritis for 5 days, and she has been vomiting, been nauseous, and had trouble taking fluids by mouth. Because she was not eating, she did not take any insulin during her illness. She becomes weak and confused and is taken to the emergency room (ER) by her parents. The ER doctor notices a fruity odor to her breath, hyperventilation, and a blood glucose level of 600 mg/dL.
A blood pH measurement is taken. You would expect this value to be which one of the following? (A) 6.75 (B) 7.15 (C) 7.40 (D) 7.65 (E) 8.00
The answer is B. The patient is exhibiting the symptoms of diabetic ketoacidosis. Normal blood pH is in the range of 7.40. Diabetic ketoacidosis reduces the blood pH since ketone bod- ies accumulate and produce acid, which the blood has trouble buffering. A mild ketoacidosis would reduce the pH to about 7.25; one in which the patient exhibits neurological changes (weak and confused) would lower the pH even further to 7.15. Life-threatening diabetic ketoacidosis would be a pH of 7.0. Answers D and E are incorrect because they represent an alkalization of the blood, which does not occur when acids accumulate.
A 14-year-old girl with Type 1 diabetes has had viral gastroenteritis for 5 days, and she has been vomiting, been nauseous, and had trouble taking fluids by mouth. Because she was not eating, she did not take any insulin during her illness. She becomes weak and confused and is taken to the emergency room (ER) by her parents. The ER doctor notices a fruity odor to her breath, hyperventilation, and a blood glucose level of 600 mg/dL.
The patient is hyperventilating because of which one of the following?
(A) The low pH of the blood
(B) The elevated pH of the blood
(C) The increased glucagon/insulin ratio in
the blood
(D) Lack of fluids in the body
(E) Difficulty in breathing due to the lack of food
The answer is A. Hyperventilation is the body’s way to try and raise the lowered blood pH by exhaling carbon dioxide rapidly. Carbon dioxide will form carbonic acid and a proton in the blood; as the carbon dioxide is exhaled, the acid and proton will associate so that the carbonic acid can form carbon dioxide and water. This will decrease the proton concentration in the blood, and raise the pH. The hyperventilation is not due to the altered hormonal ratios in the blood, the lack of fluids, or the lack of food.
