BCHM 3984 Module 5 Practice Questions

Sucrose is also represented by which one of the following?

Glucose α-1,2-fructose

When the liver is undergoing gluconeogenesis, energy is required to synthesize glucose from two molecules of lactate, which can be obtained from the red blood cells. The glucose produced can then be exported and used by the red blood cells. What is the net ATP yield for this cycle of glucose production from lactate in the liver and glucose utilization by the red blood cell?

-4 Two moles of lactate are required to form one mole of glucose. In the liver, the conversion of lactate to glucose requires 6 moles of high-energy phosphate (ATP equivalent; 2 at the pyruvate carboxylase step, 2 at the PEP carboxykinase step, and 2 at the phosphoglycerate kinase step). Because red blood cells have no mitochondria, the TCA cycle does not exist there, and glycolysis is utilized for energy production exclusively,yielding 2 ATP for every glucose. The entire lactate-glucose cycle, therefore, loses energy. Six ATPs are required to produce one glucose, but when metabolized by glycolysis in the red blood cell only, two ATPs are produced, realizing a net loss of four high-energy bonds. If the TCA cycle could be utilized, 30 ATP would be produced. Then, 30 − 6 = 24.

In an embryo with a complete deficiency of pyruvate kinase, how many net moles of ATP are generated in the conversion of one mole of glucose through glycolysis?

0 Normally, one mole of ATP is used to convert one mole of glucose to one mole of glucose-6-phosphate and a second to convert one mole of fructose-6-phosphate to the bisphosphate. Two triose phosphates are produced by cleavage of fructose-1,6-bisphosphate. As the two triose phosphates are converted to pyruvate, four ATPs are generated; two by phosphoglycerate kinase and two by pyruvate kinase. Net, two ATPs are produced. If pyruvate kinase is completely deficient, two less ATPs will be produced; thus, net ATP production will be zero. It is unlikely that the embryo would survive with a complete deficiency of this enzyme.

Carbon dioxide is a product from a reaction catalyzed by which one of the following enzymes?

6-Phosphogluconate dehydrogenase 6-Phosphogluconate is decarboxylated to form ribulose-5-phosphate, NADPH, and CO , using the enzyme 6-phosphogluconate dehydrogenase. Transketolase and transaldolase catalyze the nonoxidative reactions of the HMP shunt pathway (which do not produce NADPH or carbon dioxide). Glucose-6-phosphate dehydrogenase produces 6-phosphogluconate lactone and NADPH in the first oxidative step of the pathway.

During glycolysis, the conversion of dihydroxyacetone phosphate to pyruvate requires which one of the following?

A dehydrogenase Dihydroxyacetone phosphate is isomerized to glyceraldehyde-3-phosphate and converted in a series of steps to pyruvate. One of the reactions requires glyceraldehyde-3-phosphate dehydrogenase (G3PDH), which uses one molecule of inorganic phosphate for each molecule of NADH it produces. In the conversion of one molecule of 1,3-bisphosphoglycerate to one molecule of pyruvate, two molecules of ATP are produced (one at the phosphoglycerate kinase step, the other at the pyruvate kinase step). A phosphatase is not required during any step of glycolysis. The inorganic phosphate used by the G3PDH step ends up as the γ-phosphate of ATP and is not released as inorganic phosphate.

To help diagnose diabetes mellitus, a patient's blood is tested for an elevated level of HbA . Which one of the following most accurately describes HbA1c ?

A glycosylated fraction of hemoglobin HbA1c is a derivative of hemoglobin in that it is glycosylated. Glycosylation of hemoglobin is a nonenzymatic reaction and is dependent on the glucose levels in the red blood cell. If blood glucose levels are higher than normal (as in diabetes), then the percent of hemoglobin that is glycosylated will be higher than in individuals who do not have diabetes. Amino groups are often acetylated and can be linked to sugars, but hemoglobin does not get acetylated, acylated, or phosphorylated. Sugars such as glucose can be phosphorylated, as in glucose-6-phosphate. Oxidized hemoglobin, assuming it is the iron that is oxidized, is called methemoglobin (when iron is in the Fe3+ state).

A 6-month-old infant has been diagnosed with type II glycogen storage disease and has been placed on enzyme replacement therapy to relieve his symptoms and prolong his life. The drug being administered to the patient most likely has which one of the following properties?

A mannose-6-phosphate bound to the protein Type 2 glycogen storage disease (Pompe disease) is the lack of lysosomal α-glucosidase activity. Glycogen in the lysosomes cannot be degraded and lead to lysosomal dysfunction and a life-threatening disease. The drugLumizyme can replace the enzyme and is given by infusion. In order to target the drug to the lysosomes, it needs to contain a lysosomal targeting sequence, which is a mannose-6-phosphate linked to the protein. The enzyme has a carbohydrate-binding site (not lipid-binding site) because the normal substrate is a sugar (glycogen). The KDEL sequence targets proteins to the endoplasmic reticulum. Lumizyme needs to go to the lysosomes, not the nucleus, so it does not contain a nuclear localization sequence. The protein is also not membrane bound and does not contain an amino terminal-linked palmitate group.

Letters A through E represent enzymes that catalyze the reactions indicated. The enzyme that is phosphorylated and inactivated by protein kinase A in the liver.

A; Phosphoenolpyruvate --> Pyruvate Liver pyruvate kinase is inactivated by protein kinase A. Pyruvate dehydrogenase is inactivated by a kinase that is a subunit of the enzyme complex, because pyruvate dehydrogenase is located within the mitochondria, and pyruvate kinase is located in the cytoplasm. PKA, the enzyme that phosphorylates pyruvate kinase, is found only in the cytoplasm. Lactate dehydrogenase, aminotransferase, and pyruvate carboxylase are not regulated by phosphorylation.

Phosphorylase kinase can be best described by which one of the following?

Activated in response to: epinephrine; Target of enzyme activity: glycogen phosphorylase; Active in presence of caffeine? Yes; Required substrate for enzymatic activity: GTP Glucagon in the liver and epinephrine in both the liver and the muscle cause cAMP levels to rise, activating protein kinase A. Protein kinase A phosphorylates and activates phosphorylase kinase, which, in turn, phosphorylates and activates phosphorylase. These phosphorylation reactions require ATP. Branching enzyme is not a substrate for phosphorylase kinase. Phosphodiesterase inhibitors, such as caffeine, keep cAMP elevated, which allows protein kinase A to be active, which keeps phosphorylase kinase active and in its phosphorylated form.

A 50-year-old man with type 2 diabetes is taking glipizide to help control his blood sugar levels. One day, he could not remember whether he had taken the medication, so he accidentally took a second dose of the drug. Two hours later, he suddenly develops irritability, tremors, tachycardia, and lightheadedness. In response to the overdose of glipizide, the patient has released hormones that will lead to glucose being released by the liver. This occurs through an initial activation of which one of the following liver enzymes?

Adenylate cyclase Epinephrine, via binding to its receptor, activates a Gs-protein, which binds to and activates adenylate cyclase. Adenylate cyclase will convert ATP to cAMP. As cAMP levels increase, the cAMP binds to the regulatory subunits of protein kinase A, allowing the regulatory subunits to be released from the catalytic subunits. This activates protein kinase A, which then phosphorylates both glycogen synthase and phosphorylase kinase. Glycogen phosphorylase is activated by phosphorylation by phosphorylase kinase. Thus, of the events listed, activation of adenylate cyclase is the initial event.

A type 1 diabetic self-injected insulin prior to their evening meal, but then was distracted and forgot to eat. A few hours later, the individual fainted, and after the paramedics arrived, they did an STAT blood glucose level and found it to be 45 mg/dL. The blood glucose was so low because which one of the following tissues assimilated most of it under these conditions?

Adipose tissue Insulin stimulates glucose transport into muscle and adipose cells through mobilization of GLUT4 transporters from internal vesicles to the cell surface. Insulin does not significantly stimulate glucose transport into tissues such as the liver, brain, or RBCs, which utilize different variants of the glucose transporters. Only GLUT4 is insulin responsive.

A patient presented with a bacterial infection that produced an endotoxin that was found, after extensive laboratory analysis, to inhibit phosphoenolpyruvate carboxykinase. The patient would have very little glucose produced from which one of the following gluconeogenic precursors?

Alanine Phosphoenolpyruvate carboxykinase converts oxaloacetate to phosphoenolpyruvate. It is a gluconeogenic enzyme required for the conversion of amino acid carbons and lactate (but not phosphoenolpyruvate or glycerol) to glucose. Alanine is converted to pyruvate, which is converted to oxaloacetate for glucose production. In the absence of PEPCK activity, oxaloacetate cannot be used for glucose production. Acetyl-CoA from oxidation of fatty acids is not converted to glucose. Fructose can be converted to glucose without the need for PEPCK activity (fructose to fructose-1-phosphate, F-1-P to dihydroxyacetone phosphate and glyceraldehyde, glyceraldehyde to glyceraldehyde-3-phosphate, then the production of fructose-1,6-bisphosphate from DHAP and G3P, loss of phosphate to fructose-6-phosphate, isomerization to glucose-6-phosphate, then loss of phosphate to produce glucose).

Mr. Smith has lived with type 1 diabetes for the past 25 years. At his last annual checkup with his physician, he complained of difficulty with his vision, and your examination indicated potential cataract formation. Mr. Smith has had trouble controlling his diabetes throughout his life, with an HbA reading typically 8.0% to 8.5% (normal is less than 5.6%). An enzyme responsible for cataract formation under these conditions is which one of the following?

Aldose reductase Aldose reductase converts aldehyde sugars to sugar alcohols (ie, glucose to sorbitol or galactose to galactitol). When glucose or galactose levels are elevated, there is an increase in sorbitol or galactitol production. The lens of the eye can accumulate the elevated sugar, and when the sugar is converted to its alcohol form, it is trapped in the lens, leading to an osmotic imbalance across the lens membrane. This leads to fluid uptake by the lens, which results in a collapse of the lens fiber system, resulting in opacity. The lens does not produce collagen, so neither prolyl hydroxylase nor lysyl oxidase is involved in cataract formation. Hexokinase converts glucose to glucose-6-phosphate, which is not involved in cataract formation (in fact, as free glucose levels decrease, there is less glucose available to be converted to sorbitol). The same is true for galactokinase, which converts galactose to galactose-1-phosphate. It is only when free galactose accumulates (as in galactosemia) that galactitol can be formed, which also leads to cataract formation.

A patient had large deposits of liver glycogen, which, after an overnight fast, had shorter-than normal branches. This abnormality could be caused by a mutation in which one of the following enzymatic activities?

Amylo-1,6-glucosidase (α-glucosidase) If, after fasting, the branches were shorter-than-normal, phosphorylase must be functional and capable of being activated by glucagon. The branching enzyme (the 4:6 transferase) must be normal because the branches are present. The protein glycogenin must be present in order for large amounts of glycogen to be synthesized and deposited. The defect is most likely in the debranching enzyme (which contains an α-1,6-glucosidase activity). If the debrancher is defective, phosphorylase would break down the glycogen to the branch points, but complete degradation would not occur. Therefore, short branches would be present in the glycogen. If the short branches contain only one glucose unit, the defect is in the α-1,6-glucosidase activity of the debrancher. If they contained four glucose units, the defect would be in the 4:4 transferase activity of the debrancher. The amylo-4,6 transferase activity belongs to the branching enzyme and creates branches (breaks an α-1,4 bond and creates an α-1,6 bond). The defect described is one of the glycogen storage diseases, type III.

Letters A through E represent enzymes that catalyze the reactions indicated. The reaction that will form product (as indicated by the arrow) when NADH levels are elevated.

B; Lactate <-- Pyruvate Lactate dehydrogenase produces lactate from pyruvate when NADH levels are high. NADH inhibits pyruvate dehydrogenase (reaction C) and has no effect on the other three reactions depicted in the figure.

Which one of the following occurs in the conversion of pyruvate to glucose during gluconeogenesis?

Biotin is required as a cofactor.

A patient has been diagnosed with type 1 diabetes in their late teens and is being treated with exogenous insulin, but a second physician is not convinced that the patient has type 1 diabetes, but rather has type 2 diabetes. Measurement of which one of the following would allow the physician to determine which diagnosis is correct?

C-peptide levels The major difference between a type 1 and type 2 diabetic is the ability to produce endogenous insulin. Type 1 diabetics do not produce insulin, whereas type 2 diabetics do produce insulin, but have difficulty responding to the insulin. When insulin is synthesized as preproinsulin, it is then modified and the C-peptide is removed from the molecule, to produce active insulin. Type 1 diabetics would be lacking C-peptide(exogenous insulin that is injected also lacks C-peptide), whereas type 2 diabetics would be producing C-peptide. The levels of glucagon and epinephrine would be similar in both types of diabetes. Because the patient is on insulin already, measuring the level of mature insulin in the blood would be unhelpful. HbA1c levels measure glycemic control over the past 6 weeks and are usually elevated in both types of diabetics.Measuring HbA1c would not enable one to distinguish between type 1 and type 2 diabetes in this patient.

Letters A through E represent enzymes that catalyze the reactions indicated. The reaction that requires thiamin pyrophosphate.

C; Pyruvate --> Acetyl-CoA Pyruvate dehydrogenase requires thiamine Pyrophosphate. Thiamine pyrophosphate is involved in breaking carbon-carbon bonds, and none of the other reactions involved breaking a carbon-carbon bond. Pyruvate carboxylase, which requires biotin, creates a carbon-carbon bond.

Which one of the following best represents the structure of glycosaminoglycans?

Contain repeating disaccharide units: Yes; Overall charge on the molecule is: negative; Contain oxidized sugars: Yes; Contain sulfated sugars: Yes Glycosaminoglycans contain repeating disaccharide units and do have an overall negative charge because of the presence of oxidized sugars (generating carboxylic acids) and sulfated sugars.

Which one of the sugar-pairs are mirror images of each other?

D-Glyceraldehyde and L-glyceraldehyde D- and L-glyceraldehyde are mirror images of each other. Glucose and galactose are C-4 epimers. Ribose and ribulose are an aldose-ketose pair (both five-carbon sugars). D-Galactose and L-glucose are stereoisomers. Fructose and ribulose are not related; one is a six-carbon ketose, the other a five-carbon ketose. Xylulose and ribose are a combination of isomers (ketose-aldose) and epimers (carbon 3) of each other.

Caffeine, a methyl xanthine, has been added to a variety of cell types. Which one of the following would be expected in various cell types treated with caffeine and epinephrine?

Decreased activity of liver glycogen synthase

The major source of glucose being oxidized by cells after 6 weeks of fasting would be which one of the following?

Dietary glucose

The major source of glucose that is being oxidized by cells 1 hour after a meal would be which one of the following?

Dietary glucose Dietary glucose is the source of blood glucose for about 2 hours after a meal. At that point, glycogenolysis would take over, and after about 20 hours, glucose production would be evenly split between glycogenolysis and gluconeogenesis. Glycogen stores will be exhausted about 30 hours into a fast.

Letters A through E represent enzymes that catalyze the reactions indicated. The reaction that requires biotin.

E; Pyruvate --> Oxaloacetate Pyruvate carboxylase requires biotin, CO , and ATP. Biotin is utilized for carboxylation reactions, and none of the other enzymes catalyze a carboxylation reaction. Pyruvate dehydrogenase catalyzes an oxidative decarboxylation reaction, whereas lactate dehydrogenase catalyzes an oxidation-reduction reaction. Pyruvate kinase catalyzes a group transfer reaction, and the aminotransferase catalyzes a transamination reaction.

Letters A through E represent enzymes that catalyze the reactions indicated. The reaction that is activated by acetyl-CoA.

E; Pyruvate --> Oxaloacetate Pyruvate carboxylase is activated by acetyl-CoA, whereas pyruvate dehydrogenase (reaction C) is inhibited by acetyl-CoA. Acetyl-CoA is not an allosteric effector for any of the other enzymes such as lactate dehydrogenase (reaction B), the aminotransferase (reaction D), and pyruvate kinase (reaction A).

A 3-year-old has been a fussy eater since being weaned, particularly when fruit is part of her diet. She would get cranky, sweat, and display dizziness and lethargy, after eating a meal with fruit. Her mother noticed this correlation, and as long as fruit was withdrawn from her diet, the child did not display such symptoms. The problem the girl exhibits when eating fruit is most likely due to which one of the following?

Elevated levels of fructose-1-phosphate in liver cells The patient has hereditary fructose intolerance, which is caused by a mutation in aldolase B. Sucrose would still be cleaved by sucrase; thus, it would not increase in the stool. Fructose would not be metabolized normally; therefore, it would be elevated in the blood and urine. Aldolase B would not cleave fructose-1-P; thus, its levels would be elevated, and the product, glyceraldehyde, would not be produced.

In a glucose tolerance test, an individual in the basal metabolic state ingests a large amount of glucose. If an individual displays a normal response, this ingestion results in which one of the following?

Enhanced glycogen synthase activity in the liver After ingestion of glucose, the insulin-to-glucagon ratio increases, the cAMP phosphodiesterase is activated, cAMP levels drop, and protein kinase A is inactivated. This leads to the activation of glycogen synthase by protein phosphatase 1. The ratio of phosphorylase a and phosphorylase b is decreased by protein phosphatase 1 as well; thus, glycogen degradation decreases. Red blood cells continue to use glucose and form lactate at their normal rate because glucose is the sole energy source for such cells. CREB is also inactivated under these conditions, thereby reducing the levels of PEPCK (via transcriptional regulation) within the cell.

A positive allosteric activator of phosphofructokinase 1 in the liver is which one of the following?

Fructose-2,6-bisphosphate Phosphofructokinase 1 is activated by AMP and fructose-2,6-bisphosphate. It is inhibited by ATP and citrate and not directly affected by acetyl-CoA or ADP. In the liver, fructose-2,6-bisphosphate is the major activator.

Aspartic acid can be converted to oxaloacetate in one step (a transamination reaction), which does not require energy. How many high-energy bonds and molecules of reduced cofactors are required to convert two molecules of aspartate to one molecule of glucose?

Four high-energy bonds and two molecules of NADH In order to convert oxaloacetate to glucose, the following steps are required: oxaloacetate to PEP via PEP carboxykinase (requiring GTP), PEP to 2-PG (enolase), 2-PG to 3-PG (phosphoglucomutase), 3-PG to 1,3-BPG (requiring ATP), 1,3-BPG to G3P (requiring NADH), one G3P is isomerized to DHAP, and the two condense to form F-1,6-BP (triose phosphate isomerase and aldolase); F-1,6-BP to F6P (fructose-1,6-bisphosphatase), F6P to G6P (phosphohexose isomerase), and G6P to glucose (glucose-6-phosphatase). Overall, the conversion of oxaloacetate to glucose requires two molecules of GTP, two molecules of ATP, and two molecules of NADH.

A 9-year-old boy, at a routine physical for participation on a sports team, was found to have a positive reducing sugar test. The boy has no symptoms of any disease and has not had to alter his diet in any way. Identification of the sugar in the boy's urine would most likely indicate which one of the following?

Fructose An elevation of glucose in the urine would suggest diabetes, and the boy should be showing symptoms of type 1 diabetes. An elevation of galactose would indicate galactosemia, and the boy has no symptoms of that disorder. Lactose, sucrose, and glycogen are not found in the blood or urine. Fructose is the most likely offending compound, via essential fructosuria, a lack of fructokinase. This disorder is phenotypically benign which is why the boy did not exhibit any symptoms.

A young infant, who was nourished by a synthetic formula, had a sugar in the blood and urine. This compound gave a positive reducing sugar test but was negative when measured with glucose oxidase. Treatment of blood and urine with acid (which cleaves glycosidic bonds) did not increase the amount of reducing sugar measured. Which of the following compounds is most likely to be present in this infant's blood and urine?

Fructose Fructose gives a positive result in a reducing sugar test and a negative result in a glucose oxidase test. It is a monosaccharide and so is not cleaved by acid. Glucose gives a positive test result with the enzyme glucose oxidase. Sorbitol has no aldehyde or ketone group and thus cannot be oxidized in the reducing sugar test. Maltose and lactose are disaccharides that undergo acid hydrolysis, which doubles the amount of reducing sugar. This infant probably has benign fructosuria or the more dangerous condition, hereditary fructose intolerance. A galactose oxidase test would rule out the possibility that the sugar was galactose.

Lactose is represented by which one of the following?

Galactose β-1,4-glucose

A 1-year-old child, on a routine well child visit, was discovered to have cataract formation in both eyes. Blood test demonstrated elevated galactose and galactitol levels. In order to determine which enzyme might be defective in the child, which intracellular metabolite should be measured?

Galactose-1-phosphate The child has a form of galactosemia. The elevated galactitol enters the lens of the eye and is trapped. The difference in osmotic pressure across the lens of the eye leads to cataract formation. Galactose is phosphorylated by galactokinase to galactose-1-P, which reacts with UDPglucose in a reaction catalyzed by galactose-1-phosphate uridylyl transferase to form UDP-galactose and glucose-1-P. An epimerase converts UDP-galactose to UDP-glucose. Deficiencies in either galactokinase (nonclassical) or galactose-1-phosphate uridylyl transferase (classical) result in galactosemia, with elevated levels of galactose and galactitol (reduced galactose) in the blood. An intracellular measurement of galactose-1-phosphate can allow a definitive diagnosis to be obtained (such levels would be nonexistent if the defect were in galactokinase, and the levels would be greatly elevated if the galactose-1-phosphate uridylyl transferase enzyme were defective).

A deficiency of galactose-1-phosphate uridylyl transferase could lead to which one of the following?

Galactosemia In classical galactosemia, the galactose-1-phosphate uridylyl transferase is deficient. Galactose, galactitol, and galactose-1-phosphate accumulate when galactose is ingested. Cataracts and hypoglycemia result. Nonclassical galactosemia is caused by a defect in galactokinase.

A deficiency of an enzyme that phosphorylates a sugar could lead to which one of the following?

Galactosemia Nonclassical galactosemia is caused by a deficiency of galactokinase (an enzyme that will phosphorylate a sugar). Galactose accumulates and forms galactitol, which can lead to cataract formation. Classical galactosemia is caused by a mutation in galactose-1-phosphate uridylyl transferase (the enzyme that forms galactose-1-phosphate). Essential fructosuria is caused by a defect in fructokinase, but hereditary fructose intolerance is caused by a mutation in aldolase B.

Adenylate cyclase is indirectly regulated by which one of the following?

Glucagon receptor Glucagon binds to its membrane receptor, and the complex stimulates G-proteins that activate adenylate cyclase in the cell membrane, causing the conversion of ATP to cAMP. PDE breaks down cAMP to 5´-AMP, but does not affect adenylate cyclase activity.

Women, after giving birth, secrete the hormone prolactin, which stimulates milk production in the breast. The disaccharide produced under these conditions is composed of which two sugars?

Glucose and galactose Milk sugar or lactose is a disaccharide composed of a combination of glucose and galactose. Maltose is a dimer of two glucose residues. Sucrose is composed of glucose and fructose.

The major source of glucose being oxidized by cells after fasting for 48 hours would be which one of the following?

Glucose produced by gluconeogenesis By 2 days after a meal, liver glycogen stores have been depleted, and gluconeogenesis is the only source of blood glucose.

A glycogen branch point is represented by which one of the following?

Glucose α-1,6-glucose Glycogen branches are composed of glucose α-1,6-glucose linkages. Ninety percent of the linkages in glycogen are glucose α-1,4-glucose, which compose the straight chains and not the branch points.

After digestion of a piece of cake that contains flour, milk, and sucrose as its primary ingredients, the major carbohydrate products entering the blood are which one of the following?

Glucose, fructose, and galactose The cake contains starch, lactose (milk sugar), and sucrose (table sugar). Digestion of starch produces glucose. Lactase cleaves lactose to galactose and glucose, and sucrase cleaves sucrose to fructose and glucose. Thus, the intestinal epithelial cells will absorb from the intestinal lumen and then secrete into the blood, glucose, galactose, and fructose. The intestinal epithelial cells will not use these sugars as an energy source.

Which one of the following metabolites is used by all cells for glycolysis, glycogen synthesis, and the hexose monophosphate shunt pathway?

Glucose-6-phosphate Glucose-6-phosphate is common to all pathways. It can be converted to glucose-1-phosphate for glycogen synthesis or go directly into the pentose phosphate pathway, or proceed through fructose-6-phosphate in glycolysis. UDP-glucose is formed from glucose-1-phosphate and can be used to form glycogen, lactose, glycoproteins, and glycolipids.

A common intermediate in the conversion of glycerol and lactate to glucose is which one of the following?

Glucose-6-phosphate The only intermediate included in the list that the pathway of gluconeogenesis from glycerol has in common with the pathway of gluconeogenesis from lactate is glucose-6-phosphate. Glycerol enters gluconeogenesis as dihydroxyacetone phosphate. Therefore, it bypasses the other compounds (pyruvate, oxaloacetate, malate, and phosphoenolpyruvate) through which the carbons of lactate must pass on its pathway to glucose synthesis.

NADPH and lactone are products from a reaction catalyzed by which one of the following enzymes?

Glucose-6-phosphate dehydrogenase Both glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6-PGDH) produce NADPH, but only G6PDH produces 6-phosphogluconolactone. 6-Phosphgluconolactone is a substrate for 6-PGDH. Transaldolase and transketolase catalyze the nonoxidative reactions of the HMP shunt pathway. The nonoxidative reactions of the pathway do not produce NADPH

A liver cell line has been created that contains a temperature-sensitive protein kinase A. At 32°C, the protein works normally, but at 42°C, the protein has lost the ability to bind its allosteric regulator. If the cell line is treated with glucagon at 42°C, which one of the following pathways would contain enzymes in their inactive state?

Glycogen degradation At the higher temperature, protein kinase A cannot bind cAMP and, therefore, remains in an inactive state. This means that the proteins that are normally phosphorylated by PKA are not at the nonpermissive temperature. These enzymes include PFK-2 (activating the phosphatase such that fructose-1,6-bisphosphate levels drop), pyruvate kinase (inactivating it), glycogen synthase (inactivating it), glycogen phosphorylase kinase (activating it), and protein inhibitor 1 (allowing it to bind to protein phosphatase 1, thereby inhibiting the phosphatase). Because none of these phosphorylation events can occur, glycolysis will remain active, glycogen synthesis will remain active, glycogen degradation will be inhibited, and the HMP shunt enzymes and enzymes of the TCA cycle will not be affected by the inability of PKA to phosphorylate its substrates.

The mucopolysaccharidoses are caused by deficiencies of enzymes involved in the degradation of which one of the following classes of molecules?

Glycosaminoglycans Glycosaminoglycans (formerly called mucopolysaccharides) are the long, linear polysaccharide chains of proteoglycans. They are synthesized and secreted by cells. Ultimately, they are taken up by cells via endocytosis and degraded by lysosomal enzymes. A deficiency of any one of these lysosomal enzymes can result in a mucopolysaccharidosis (e.g., Hurler, Hunter). Mucopolysaccharidoses are not caused by defects in degrading glycoproteins, glycogen, disaccharides, or monosaccharides. The lysosomal enzymes that are defective in the mucopolysaccharidoses remove a specific sugar from the polysaccharide chains of the glycosaminoglycans. If the sugar cannot be removed, the next enzyme of the pathway cannot function, and the partially digested material accumulates in the lysosome, eventually blocking lysosomal function.

A patient presented with a bacterial infection that produced an endotoxin that was found, after extensive laboratory analysis, to inhibit phosphoenolpyruvate carboxykinase. Administration of a high dose of glucagon to this patient 30 hours after a high-carbohydrate meal would result in which one of the following?

Have little effect on blood glucose levels Thirty hours after a meal, liver glycogen is normally depleted, and blood glucose is maintained solely by gluconeogenesis after this time. However, in this case, a key gluconeogenic enzyme is inhibited by an endotoxin. Therefore, gluconeogenesis will not occur at a normal rate, and glycogen stores will be depleted more rapidly than normal. Blood glucose levels will not change significantly if glucagon is administered after 30 hours of fasting.

A deficiency of glucose-6-phosphate dehydrogenase activity could lead to which one of the following?

Hemolytic anemia A glucose-6-phosphate dehydrogenase deficiency results in a hemolytic anemia because adequate levels of NADPH are not produced by the pentose phosphate pathway. NADPH is required for the reduction of oxidized glutathione, which helps to prevent oxidative damage to red blood cell membranes. A deficiency of any of the other enzymes listed would not lead to hemolytic anemia.

A deficiency of aldolase B activity could lead to which one of the following?

Hereditary fructose intolerance A deficiency of aldolase B results in fructose intolerance. Fructose-1-phosphate accumulates because it is not cleaved. Hypoglycemia results from the accumulation of fructose-1-phosphate. The glycolytic reaction catalyzed by aldolase B (the splitting of fructose-1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde-3-phospahte) is not affected to an appreciable extent because the liver may express another enzyme of aldolase that can carry out the glycolytic reaction.

A 6-month-old infant was having trouble sleeping, exhibited lethargy, exhibited hepatosplenomegaly, and analysis of her blood showed elevated levels of uric acid and lactic acid. The child exhibited fasting hypoglycemia shortly after a normal meal. The elevation of uric acid occurs, in part, due to which one of the following?

Increased activity of the HMP shunt pathway The child lacks glucose-6-phosphatase activity (type 1 glycogen storage disease). As glucose-6-phosphate accumulates (from gluconeogenesis or glycogen degradation), the high levels of G6P force both glycolysis forward (producing lactic acid) and the HMP shunt pathway (producing more purines via the synthesis of ribose-5-phosphate, leading to uric acid production because of excess purine degradation). Glycogen synthesis is increased because of high G6P levels (allosteric activation of glycogen synthase D), but such an increase does not lead to uric acid production. Increasing activity of the TCA cycle will also not affect purine and uric acid production.

The symptoms and labs are classic for insulinoma. An insulinoma is a tumor of the pancreatic β-cells that episodically releases large amounts of insulin. At those times, the patient experiences the symptoms of hypoglycemia. A pheochromocytoma is a tumor of the adrenal gland that episodically releases epinephrine and norepinephrine throughout the body. A pheochromocytoma would not lead to hypoglycemia (epinephrine stimulates the liver to export glucose), or high insulin or C-peptide levels. If the patient were injecting insulin, the C-peptide should be low because exogenous insulin lacks the C-peptide. Neither a liver tumor nor a carcinoid tumor would release insulin to the blood.

Increased sorbitol in the lens Fluctuating levels of sugars and sugar alcohols in the lens can cause fluctuating visual acuity. With high blood glucose, there would be increased levels of sorbitol in the lens. The lens does not contain mitochondria and cannot use the TCA cycle/electron transport chain togenerate energy. Galactitol causes the same problems as sorbitol, but galactitol is derived from galactose, whereas sorbitol is produced from glucose. The patient has high glucose levels, so galactitol would not be expected to accumulate in the lens. Macular degeneration affects the retina, but in this case, it is the lens that is the affected tissue. Reducing fructose levels in the lens would reduce sorbitol levels, which would ease the visual acuity problem, not make it occur.

A mad scientist has developed a poison that blocks sorbitol dehydrogenase in vivo. He uses the poison on every man who rivals him for his girlfriend. Which of the following is the most likely result in these poisoned men?

Infertility Glucose is reduced to sorbitol by aldose reductase, and sorbitol is then oxidized at carbon 2 by sorbitol dehydrogenase to form fructose. Fructose derived from glucose in the seminal vesicles is the major energy source for sperm. Without it, the men would have nonmobile sperm and be effectively infertile. Testosterone would not be affected nor would regular glucose metabolism, so none of the other listed side effects would occur. Diabetics could develop cataracts by excess sorbitol from lack of sorbitol dehydrogenase, but the lack of sorbitol dehydrogenase would not cause diabetes.

Which one of the following is a regulatory mechanism employed by muscle for glycolysis?

Inhibition of hexokinase by its product Hexokinase is inhibited by its product, glucose-6-phosphate. PFK1 is activated by AMP and fructose-2,6-bisphosphate (F-2,6-P). F-2,6-P does not inhibit glucokinase, nor is glucokinase present in the muscle. Aldolase is not inhibited by its substrate, fructose-1,6-bisphosphate. Pyruvate kinase is inactivated by glucagon-mediated phosphorylation in the liver, but not in the muscle. The muscle isozyme of pyruvate kinase is not a substrate for protein kinase A. In addition, muscle cells do not respond to glucagon because they do not express glucagon receptors.

A patient with type 2 diabetes, and who is taking metformin for glycemic control, responds to glucagon release by stimulating glycogen degradation in which one of the following cell types?

Liver Glucagon acts on liver cells to stimulate glycogen degradation. Epinephrine acts on muscle (and liver). There are no glycogen stores inRBCs, and the amount in the brain is very low. Muscle cells lack glucagon receptors so will not activate glycogen degradation in response to glucagon release.

A 50-year-old man with a history of coronary artery disease presents with episodes of lightheadedness, tremors, palpitations, hunger, headache, weakness, and confusion. He is fine between episodes. He had such an episode at his last doctor's visit, at which time blood was drawn for various analyses. The lab results revealed high insulin, high C-peptide, and low blood glucose. Which of the following would be most consistent with his symptoms and lab values?

Insulinoma The symptoms and labs are classic for insulinoma. An insulinoma is a tumor of the pancreatic β-cells that episodically releases large amounts of insulin. At those times, the patient experiences the symptoms of hypoglycemia. A pheochromocytoma is a tumor of the adrenal gland that episodically releases epinephrine and norepinephrine throughout the body. A pheochromocytoma would not lead to hypoglycemia (epinephrine stimulates the liver to export glucose), or high insulin or C-peptide levels. If the patient were injecting insulin, the C-peptide should be low because exogenous insulin lacks the C-peptide. Neither a liver tumor nor a carcinoid tumor would release insulin to the blood.

Insulin is essential for blood glucose to enter muscle cells. Once inside the muscle cell, what is the immediate fate of the glucose?

It is converted to glucose-6-phosphate by hexokinase. The conversion of glucose to glucose-6-phosphate is catalyzed by the family of hexokinases, for which there are a number of isozymes. Muscle uses hexokinase, and the liver and pancreas use glucokinase. Myokinase is the enzyme that converts ATP + AMP to two molecules of ADP and has nothing to do with glucose. Glucose-1-phosphate is produced from glucose-6-phosphate by the enzyme phosphoglucomutase. There is no kinase that can convert glucose to glucose-1-phosphate directly.

A 3-month-old infant, who was experiencing seizures, was diagnosed with a GLUT1 deficiency, resulting in reduced glucose uptake into the brain. As a result, which one of the following substrates was providing energy for the brain?

Ketone bodies The brain can only use glucose or ketone bodies as an energy source. Even though the heart can use lactate for energy, the brain does not do so. If glucose levels are low, the only available substrate would be ketone bodies. Fatty acids will not cross the blood-brain barrier and are not a good energy source for the brain. The liver will convert fatty acids to ketone bodies for use by the brain. Amino acids are a good source of carbon for gluconeogenesis, but the brain does not oxidize amino acids at an appreciable rate. Glycerol cannot be used by the brain as an energy source because the brain lacks glycerol kinase, a necessary enzyme in the metabolism of glycerol. The treatment for a GLUT1 deficiency is a ketogenic diet—one high in fats such that ketone bodies are continuously generated to provide a fuel for the brain.

Hereditary fructose intolerance can lead to fasting hypoglycemia after eating fructose-containing food due to which one of the following?

Lack of substrate for glycogen phosphorylase Hereditary fructose intolerance is caused by a mutation in the aldolase B protein, which leads to an inability to convert fructose-1-phosphate (the product of the fructokinase reaction) to glyceraldehyde and dihydroxyacetone phosphate. The fructokinase reaction is a low Km and high Vmax enzyme and works very rapidly, thereby depleting ATP levels. Oxidative phosphorylation regenerates the ATP, thereby depleting inorganic phosphate levels. The inorganic phosphate is depleted because it is trapped in the fructose-1-phosphate, which cannot continue throughglycolysis. Glycogen phosphorylase requires inorganic phosphate to catalyze the release of glucose-1-phosphate from glycogen, so with low inorganic phosphate, the glycogen phosphorylase reaction is significantly reduced. Gluconeogenesis is also reduced because of a lack of ATP in the liver (because of the fructokinase reaction). The disorder does not affectthe number of GLUT2 transporters in the membrane. ATP is not required for glycogen degradation (Pi is). There are plenty of substrates for gluconeogenesis—what's lacking is the energy to synthesize glucose because of the speed of the fructokinase reaction using available ATP. Uric acid blocks lactate resorption from the kidneys, but does not affect glycogen degradation.

A woman undergoing chemotherapy for breast cancer has developed bloating, diarrhea, and excess gas whenever she drinks milk. She never had that problem before. The symptoms the woman is experiencing is because of a reduced synthesis of which one of the following enzymes?

Lactase Lactase converts lactose (milk sugar) to glucose and galactose. In the absence of lactase activity (the chemotherapy is destroying rapidly growing cells, such as the intestinal epithelial cells, where lactase is found), the lactose enters the colon, where the bacterial flora metabolizes it to produce gases and acids. The gases produce flatulence, and the acids lead to an osmotic imbalance that drives water to leave the colonic epithelium and enter the lumen of the colon, leading to the diarrhea. Sucrase converts sucrose (table sugar) to glucose and fructose. Amylase helps digest plant starches. Isomaltase releases glucose residues from branched oligosaccharides. Trehalase splits trehalose, which is glucose α-1,1-glucose (a disaccharide).

A deficiency of an enzyme found on the surface of intestinal epithelial cells could lead to which one of the following?

Lactose intolerance A lactase deficiency results in lactose intolerance, which is characterized by gas, bloating, and watery diarrhea following lactose ingestion. Lactase is found on the brush-border membrane of intestinal epithelial cells.

In which one of the following compounds do carbons derived from pyruvate leave the mitochondria for the synthesis of glucose during fasting?

Malate Pyruvate within the mitochondria is converted to oxaloacetate by pyruvate carboxylase, which is then reduced to malate, which can cross the mitochondrial membrane. Oxaloacetate and acetyl-CoA cannot. Lactate is produced from pyruvate in the cytosol. The reverse reaction is involved in gluconeogenesis. Glutamine is not derived from pyruvate during gluconeogenesis. Oxaloacetate can also be converted to aspartate, which can cross the mitochondrial membrane to provide carbons for gluconeogenesis.

A middle-aged man of Mediterranean ancestry has developed hemolytic anemia in the past when given drugs to prevent malaria and also when he ate a large serving of fava beans. He does have the ability, however, to synthesize fatty acids from excess carbohydrate. This is due to the generation of NADPH by which one of the following enzymes?

Malic enzyme The man has the symptoms of glucose-6-phosphate dehydrogenase deficiency as a result of the lack of NADPH in the red blood cells and the inability of the cells to regenerate reduced glutathione to protect the red blood cell membranes from oxidative damage. Fatty acid synthesis also requires NADPH, but the liver can generate NADPH from malic enzyme, an enzyme that is absent in red blood cells. Because the patient lacksglucose-6-phosphate dehydrogenase activity, answer A is incorrect, and the substrate for 6-phosphogluconate dehydrogenase is produced from the glucose-6-phosphate dehydrogenase reaction, so answer B is incorrect because of lack of substrate. None of the other enzymes listed (except for malic enzyme) utilize NADP as a substrate and generate NADPH.

A patient has a genetic defect that causes intestinal epithelial cells to produce disaccharidases of much lower activity than normal. Compared with a normal person, after eating a bowl of milk and oatmeal sweetened with table sugar, this patient will have higher levels of which one of the following?

Maltose, sucrose, and lactose in the stool In this patient, starch will be digested by salivary and pancreatic α- amylases to small oligosaccharides and maltose, but a lower-than-normal amount of glucose will be produced because of the deficiency of the brush-border disaccharidases, which have maltase, so maltase, sucrase, and lactase activity. Sucrose and lactose will not be cleaved. There will be more maltose, sucrose, and lactose in the stool and less monosaccharides in the blood and tissues. Insulin levels will be lower than-normal because of the reduced levels of glucose entering the blood. Muscle glycogen will not increase because there is less glucose in the circulation, and insulin, which is required for glucose entry into the muscle, may not be secreted under these conditions.

The immediate degradation of glycogen under normal conditions gives rise to which one of the following?

More glucose-1-phosphate than glucose Phosphorylase produces glucose-1-phosphate from glucose residues-linked α-1,4. Free glucose is produced from α-1,6-linked residues at branch points by an α-1,6-glucosidase activity of the debranching enzyme. Degradation of glycogen produces glucose-1-phosphate and glucose in about a 10:1 ratio, which is the ratio of the α-1,4 linkages to α-1,6 linkages.

Dietary fructose is phosphorylated in the liver and cleaved to form which one of the following?

One molecule each of dihydroxyacetone phosphate and glyceraldehyde Fructose-1-phosphate is cleaved by aldolase B to dihydroxyacetone phosphate and glyceraldehyde. The glyceraldehyde is phosphorylated by triose kinase to form glyceraldehyde-3-phosphate, which enters the glycolytic pathway.

Phosphorylase b is regulated directly by which one of the following proteins?

Phosphorylase kinase Phosphorylase kinase phosphorylates phosphorylase b, converting it to the more active phosphorylase a, which releases glucose-1-P from glycogen. PKA does not directly phosphorylate glycogen phosphorylase. Binding of glucagon to its receptor will lead to the activation of adenylate cyclase (through a G-protein signaling pathway), which produces cAMP, which activates protein kinase A. Phosphodiesterase (PDE) hydrolyzes the cyclic bond in cAMP, producing 5´-AMP.

Which one of the following is most likely in an individual at rest who has fasted for 12 hours?

Phosphorylase, pyruvate kinase, and glycogen synthase are all in their phosphorylated states in the liver. After 12 hours of fasting, liver glycogen stores are still substantial. The insulin-to-glucagon ratio is low, indicating decreasing blood glucose levels. Glycogenolysis is stimulated by glucagon, which activates adenylate cyclase. cAMP activates protein kinase A, which phosphorylates phosphorylase kinase, pyruvate kinase, and glycogen synthase. As a result, phosphorylase is activated, whereas glycogen synthase and pyruvate kinase are inactivated. Gluconeogenesis does not become the major process for maintaining blood glucose until 18 to 20 hours of fasting. After about 30 hours, liver glycogen is depleted.

Mary Smith, a patient with type 1 diabetes mellitus, has a fasting blood glucose level of 160 mg/dL and an HbA1c of 10%. These tests indicate that her current glycemic control is best described by which one of the following?

Poor, and has been poor during the past 6 weeks Mary Smith's blood glucose is currently above the range for normal fasting blood glucose (80-100 mg/dL). Her HbA1c is also above the normal 6%. Therefore, her glycemic control is poor at present and has been poor over the past 6 weeks, as reflected by her elevated HbA1c levels.

Phosphorylase kinase is directly regulated by which one of the following?

Protein kinase A A cAMP-dependent protein kinase (protein kinase A) phosphorylates phosphorylase kinase, causing it to become active. The glucagon receptor leads to the activation of adenylate cyclase (through a G-protein signaling pathway), raising cAMP levels and activating protein kinase A. PDE reverses the activation of PKA by reducing cAMP levels (hydrolysis of the cAMP to 5´-AMP).

A 65-year-old patient complains of occasional swelling, pain, and a scraping sensation in the knees. X-rays show a narrowing of the joint space. The patient only wants to take "natural" oral products to help reverse this condition. The products available for consumption are examples of which one of the following types of compounds?

Proteoglycan The patient has osteoarthritis and wants to use glucosamine/chondroitin sulfate to provide cushioning in the joint. These molecules are proteoglycans, which consist of long, linear chains of glycosaminoglycans attached to a core protein. Each chain is composed of repeating disaccharides, but disaccharides are, by definition, only two sugars. A polyol is a polyalcohol. A glycolipid is a sphingolipid and does not contribute to joint stability. The typical glycoproteins are not found in the joints, nor are they available as oral supplements as the proteoglycans are.

A 3-month-old infant was cranky and irritable, became quite lethargic between feedings, and began to develop a pot-belly. Physical examination demonstrated an enlarged liver, whereas blood work taken between feedings demonstrated elevated lactate and uric acid levels, as well as hypoglycemia. This child most likely has a mutation in which one of the following enzymes?

Pyruvate kinase The child has the symptoms of von Gierke disease, which is caused by a lack of glucose-6-phosphatase activity. In this disorder, neither liver glycogen nor gluconeogenic precursors (e.g., alanine and glycerol) can be used to maintain normal blood glucose levels. The last step (conversion of glucose-6-phosphate to glucose) is deficient for both glycogenolysis and gluconeogenesis. Muscle glycogen cannot be used to maintain blood glucose because muscle does not contain glucose-6-phosphatase. A defective liver glycogen phosphorylase (Her disease) will not affect theability of the liver to raise blood glucose levels by gluconeogenesis. In addition, the lack of liver glycogen phosphorylase does not lead to lactic and uric acid accumulation, although mild fasting hypoglycemia can be observed. Defects in liver glycogen synthase (type 0 glycogen storage disease) will lead to an early death, with hypoglycemia and hyperketonemia observed. Muscle does not contribute to blood glucose levels, so a defect in muscle glycogen phosphorylase (McArdle disease) will not lead to the observed symptoms, but will lead to exercise intolerance. A defect in pyruvate kinase will lead to hemolytic anemia, but not the other symptoms observed in the patient.

A 20-year-old patient, new to your practice, has recently moved to the area. He reports that he has hereditary fructose intolerance and wants to review which foods he can and cannot consume. Which one of the following foods can he safely ingest?

Skim milk Milk sugar is lactose, composed of glucose and galactose. Peas, sweet potatoes, and sugar beets are vegetables that contain significant levels of fructose. Cane sugar is sucrose, composed of glucose and fructose. Honey is very high in fructose, as is maple syrup.

Which one of the following best represents the structure of glycoproteins?

Structure of oligosaccharide chains: branched; Requires dolichol for synthesis: some glycoproteins; Always contain an overall positive charge: No; Are exclusively secreted proteins: No Glycoproteins contain branched oligosaccharide chains. These chains may be synthesized by addition of sugars one at a time to serine or threonine residues of the protein, or they may be synthesized on dolichol phosphate and transferred en bloc to asparagine residues on the protein.Glycoproteins are not necessarily positively charged and can be either membrane-bound, secreted, or lysosomal proteins.

A couple and their two sons were going to visit Panama in the summer and obtained drugs from friends (who had these leftover from their trip the year before) to help combat the possibility of acquiring the malarial parasite while in that country. The family members took one drug every day while visiting, then, once they arrived back home, they had to continue the drug treatment for an additional week. During the trip, one of the sons complained of being tired; after the family returned home, he was even more tired and complained of pain in his upper abdomen. He was taken to the emergency department where it was determined that he was anemic. Careful examination demonstrated a slight yellowing in the whites of his eyes. In the presence of the drug, the boy had difficulty in carrying out which one of the following reactions?

The conversion of oxidized glutathione to reduced glutathione The boy lacks glucose-6-phosphate dehydrogenase activity (an X-linked disorder) and, in response to the drug (most likely primaquine), has developed a hemolytic anemia because of an inability to regenerate reduced glutathione to protect red blood cell membranes from oxidative damage. The yellow in the eyes is as a result of a buildup of bilirubin because the released hemoglobin from the red blood cells cannot beadequately metabolized by the liver and converted to the more soluble diglucuronide form. The abdominal pain may be caused by bilirubin stones being formed in the gallbladder. Glucose-6-phosphate dehydrogenase produces NADPH in the red blood cells, which is required for glutathione reductase, the enzyme that converts oxidized glutathione to reduced glutathione. The drug does not block heme synthesis, the absorption of iron, or affect radical oxygen species metabolism (superoxide dismutase or catalase).

A woman has been diagnosed with classical galactosemia. She will be able to catalyze which one of the following reactions or reaction pathways?

The formation of galactose-1-phosphate from galactose The woman has a galactose-1-phosphate uridylyl transferase deficiency (classic galactosemia) because she can phosphorylate galactose but cannot react galactose-1-phosphate with UDP-glucose to form UDPgalactose and glucose-1-phosphate. Therefore, she will not be able to convert galactose to UDP-galactose, liver glycogen, or blood glucose. Cellular galactose-1-phosphate and blood galactose levels will be elevated if she consumes galactose or lactose. There is no straightforward pathway to convert galactose to fructose-1-phosphate.

An adolescent patient with a deficiency of muscle phosphorylase was examined while exercising her forearm by squeezing a rubber ball. Compared with a normal person performing the same exercise, this patient would exhibit which one of the following?

The patient displayed decreased lactate levels in blood drawn from her forearm. This patient has McArdle disease, a glycogen storage disease caused by a deficiency of muscle glycogen phosphorylase. Because she cannot degrade glycogen to produce energy for muscle contraction, she becomesfatigued more readily than a normal person, the glycogen levels in her muscle will be higher than normal, and her blood lactate levels will be lower. She will use more blood glucose; thus, her blood glucose levels will be decreased. The patient's glycogen structure would be normal.

A pregnant woman who has a lactase deficiency and cannot tolerate milk in her diet is concerned that she will not be able to produce milk of sufficient caloric value to nourish her baby. The best advice to her is which one of the following?

The production of lactose by the mammary gland does not require the ingestion of milk or milk products. The woman will be able to breastfeed her baby because she can produce lactose from amino acids and other carbohydrates. She will not have to eat pure galactose, or even lactose, to do so. Glucose, which can be provided by gluconeogenesis or obtained from the diet, can be converted to UDP-galactose (Glucose → glucose-6-phosphate → glucose-1-phosphate → UDP-glucose → UDP-galactose). UDP-galactose reacts with free glucose to form lactose. α-Lactalbumin is a protein that serves as the modifier of galactosyl transferase, which catalyzes this reaction. The amino acids of α-lactalbumin can be used to produce glucose, but the immediate products of α-lactalbumin degradation are not lactose. Carbohydrates cannot be synthesized from fats.

A 16-year-old patient with type 1 diabetes mellitus was admitted to the hospital with a blood glucose level of 400 mg/dL. (The reference range for blood glucose is 80-100 mg/dL.) One hour after an insulin infusion was begun, her blood glucose level had decreased to 320 mg/dL. One hour later, it was 230 mg/dL. The patient's glucose level decreased because the infusion of insulin led to which one of the following?

The stimulation of the conversion of glucose to glycogen and triacylglycerol in the liver Blood glucose decreases because insulin stimulates the transport of glucose into muscle and adipose cells and the conversion of glucose to glycogen and triacylglycerols in the liver. Ketone bodies are not made from blood glucose. During fasting, when the liver is producing ketone bodies, it is also synthesizing glucose. Carbon for ketone body synthesis comes from fatty acids. Insulin stimulates glycogen synthesis, not glycogenolysis. Muscle glycogen is not converted to blood glucose.

A patient with type 1 diabetes mellitus lacks insulin production. One consequence of this is that when blood glucose levels rise (such as after eating), the muscle cells cannot take up glucose from the circulation to be converted to glucose-6-phosphate. Which one of the following statements about glucose-6-phosphate metabolism is the most accurate?

Through UDP-glucose, it is used for the synthesis of glycogen. When glucose enters muscle cells (a step dependent on insulin), it is converted to glucose-6-phosphate. Glucose-6-phosphate can enter glycolysis, producing NADH, ATP, and pyruvate, or it can enter the pentose phosphate pathway, which produces five-carbon sugars and NADPH. Glucose-1-phosphate does not enter the pentose phosphate shunt pathway. Proteoglycans require nucleotide sugars for their synthesis, not intermediates of glycolysis. Glucose-6-phosphate can be converted to glucose-1-phosphate by phosphoglucomutase, which can then be converted to UDP-glucose, which is required for glycogen synthesis (and proteoglycan synthesis). UDP-glucose is not used to produce either NADH or NADPH.

A liver cell has been induced to synthesize a large number of proteins, but it is not synthesizing fatty acids. Which of the following enzymes would be utilized in the HMP shunt pathway under these conditions?

Transaldolase and Transketolase Under the conditions imposed upon the liver cell, the cell will require purine nucleotides in order to synthesize RNA, but will not require NADPH for fatty acid synthesis. Because deoxyribonucleotides are not required, NADPH is not needed for the thioredoxin reductase reaction (required for ribonucleotide reductase to function). Thus, the oxidative reactions ofthe pathway are not required (glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), but the enzymes for the nonoxidative reactions are required (transketolase, transaldolase, C3 epimerase, and the isomerase).

Glyceraldehyde-3-phosphate, in a reaction requiring thiamine pyrophosphate, is a product of a reaction catalyzed by which one of the following enzymes?

Transketolase Both transaldolase and transketolase produce glyceraldehyde-3-phosphate, but only transketolase requires thiamine pyrophosphate. The oxidative steps of the HMP shunt, as catalyzed by glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, do not generate glyceraldehyde-3-phosphate.

A chronic alcoholic has recently had trouble with their ability to balance, becomes easily confused, and displays nystagmus. Assay of which of the following enzymes can determine a biochemical reason for these symptoms?

Transketolase The patient has the symptoms of beriberi, which is caused by a thiamine deficiency. Of the enzymes listed, transketolase would be less active because it requires thiamine pyrophosphate as a cofactor. The other enzymes listed do not require cofactors except for the three dehydrogenases, which require either NAD or NADP , depending on the enzyme.

The longer a person chews bread in their mouth, the sweeter it seems to taste. This is because salivary amylase catalyzes which one of the following?

α-1,4-Linked units of amylose to free glucose Salivary amylase acts on starch (the storage form of plant carbohydrates) cleaving the α-1,4 linkages (but not 1,6 linkages) between glucose residues, releasing free glucose from the polymer. Humans cannot cleave β-1,4 bonds (fiber). Sucrose, lactose, and maltose are disaccharides (not starch) and are not a substrate for salivary amylase, but they are hydrolyzed by enzymes in the brush border of the intestine.

Which one of the following statements concerning lactose synthesis is correct?

α-Lactalbumin acts as a modifier of galactosyl transferase. UDP-galactose reacts with glucose to form lactose only in the mammary gland. α-Lactalbumin acts as a modifier of the enzyme galactosyl transferase, lowering its K for glucose. Glucose can be converted to UDP-glucose and epimerized to form the UDP-galactose used in lactose synthesis; therefore, dietary galactose is not required.