Chapter 16 Glycolysis and Gluconeogenesis

Matching Questions
Use the following to answer questions 1-10: Choose the correct answer from the list below. Not all of the answers will be used. a) obligate anaerobes b) AMP c) Embden Meyerhof pathway d) NAD+ e) gluconeogenesis f) UDP-glucose g) GLUT5 h) facultative anaerobes i) ATP j) magnesium k) galactosemia l) biotin 1 ____________ This is the process by which noncarbohydrate precursor molecules are converted into glucose. Ans: e Section: Introduction 2 ____________ This is another name for glycolysis. Ans: c Section: Introduction 3 ____________ These organisms cannot survive in the presence of oxygen. Ans: a Section: 16.1 4 ____________ This substance must be regenerated for glycolysis to proceed. Ans: d Section: 16.1 5 ____________ This intermediate is necessary for the conversion of galactose to glucose. Ans: f Section: 16.1 6 ____________ This molecule is an allosteric inhibitor of phosphofructokinase. Ans: i

Chapter 16 Glycolysis and Gluconeogenesis Section: 16.1 7 ____________ This transporter is responsible for fructose uptake in the intestine. Ans: g Section: 16.2 8 ____________ This condition is a result of a genetic deficiency of a single transferase enzyme. Ans: k Section: 16.1 9 ____________ This essential nutrient is required for the carboxylation of pyruvate in humans. Ans: l Section: 16.3 10 ____________ This is an allosteric activator of glycolysis. Ans: b Section: 16.1

Fill in the Blank Questions

11 Glycolysis produces a net of ________ moles of ATP per one mole of glucose. Ans: 2, two Section: 16.1 12 Pancreatic ______________ is the digestive enzyme primarily responsible for the hydrolysis of dietary plant starch. Ans: -amylase Section: Introduction 13 The key enzyme that regulates the pace of glycolysis is ____________________. Ans: phosphofructokinase Section: 16.1 14 The catalytic mechanism of the isomerization of a ketose into an aldose proceeds through an _________________ intermediate. Ans: enediol Section:16.1 15 The common structural domain of NAD+ binding dehydrogenases is often called a ___________________ after the scientist who first recognized it. Ans: Rossmann fold Section: 16.1 16 In alcoholic fermentation, the decarboxylation of pyruvate requires a coenzyme that contains the vitamin ______________. Ans: thiamine or B1 Section: 16.1

Chapter 16 Glycolysis and Gluconeogenesis 17 A potent allosteric activator of liver phosphofructokinase is _____________________, which is produced from fructose-6-phosphate by PFK2. Ans: fructose-2,6-bisphosphate Section:16.2 18 In the absence of oxygen, _____________________ increases the expression of most glycolytic enzymes and the glucose transporters GLUT1 and GLUT3. Ans: HIF-1, or hypoxia-inducible transcription factor Section: 16.2 19 The ________________ cycle refers to the metabolic reactions by which glucose is converted into lactate in skeletal muscle, and then lactate converted back into glucose in the liver. Ans: Cori Section: 16.4 20 The first step in gluconeogenesis is the ___________________ of pyruvate to form oxaloacetate. Ans: carboxylation Section:16.3

Multiple Choice Questions

21 Which of the following are reasons that glucose is a common metabolic fuel used by living organisms? A) It has a stable ring structure and is unlikely to glycosylate proteins. B) It has been found as one of the monosaccharides formed under prebiotic conditions. C) It is the only sugar used by the brain. D) a and b E) a, b, and c Ans: D Section: Introduction 22 What is the purpose of phosphorylating glucose in cytosol? A) to trap glucose in the cell B) to destabilize glucose and facilitate the next series of metabolic steps C) to convert it to a more soluble form D) All of the above. E) a and b Ans: E Section: 16.1 23 What two 3-carbon molecules are generated by the cleavage of fructose-1,6-bisphosphate? A) glyceraldehyde-3-phosphate and 3-phosphoglycerate B) glyceraldehyde-3-phosphate and dihydroxyacetone phosphate C) pyruvate and phosphoenolpyruvate D) enolase and 2-phosphoglycerate E) glyceraldehyde-3-phosphate and pyruvate Ans: B Section: 16.1 24 What is a common mechanistic feature of kinases? A) Phosphoryl groups are transferred from AMP to an acceptor. B) Binding of substrate induces cleft closing. C) All phosphorylate monosaccharides. D) All of the above. E) None of the above.

Chapter 16 Glycolysis and Gluconeogenesis Ans: B Section: 16.1

25 What reaction is catalyzed by aldolase? A) isomerization of DHAP to GAP B) ligation of GAP and DHAP C) reversible cleavage of F-1,6-BP to DHAP and GAP D) cleavage of DHAP to GAP E) irreversible aldol condensation of DHAP and GAP Ans: C Section: 16.1 26 What is the function of glyceraldehyde 3-phosphate dehydrogenase? A) oxidation by NAD+ and formation of acyl-phosphate B) oxidation of the alcohol to an aldehyde C) dehydration and dephosphorylation of GAP D) hydrolysis of GAP E) None of the above. Ans: A Section: 16.1 27 What is the function of a thioester intermediate such as the one formed from GAP? A) It speeds up the actual reaction so that more product can be made. B) The thioester shifts the equilibrium of the first stage of the reaction. C) The thioester allows the two-step reaction to be coupled so the second reaction, the energetically unfavorable phosphorylation, can proceed. D) The thioester intermediate induces a conformational change that alters the enzyme specificity. E) The thioester prevents the formation of metabolically unfavorable side products. Ans: C Section: 16.1 28 What is substrate level phosphorylation? A) phosphorylation of AMP by ATP B) ATP synthesis when the phosphate donor is a substrate with high phosphoryl transfer potential C) phosphorylation of glycolytic intermediates D) phosphorylation of ATP coupled to an ion gradient E) ATP and AMP synthesis from two molecules of ADP Ans: B Section: 16.1 29 What is the additional metabolite that is required for the conversion of 3-phosphoglycerate to 2phosphoglycerate? A) 1-phosphoglycerate D) 2,3-bisphosphoglycerate B) diacylglycerol E) 1,3-bisphosphoglycerate C) NADH Ans: D Section: 16.1 30 What are the primary metabolic fates of pyruvate? A) ethanol D) B) lactate E) C) acetyl CoA Ans: D Section: 16.1 All of the above. None of the above.

Chapter 16 Glycolysis and Gluconeogenesis 31 Fructose can enter glycolysis at two distinct points, depending on the tissue. How is fructose metabolized in adipose tissue? A) Fructose is cleaved to two molecules of GAP. B) Fructose is converted to fructose-1-phosphate. C) Fructose is converted to fructose-6-phosphate. D) Fructose is cleaved to GAP and DHAP. E) Fructose is converted to glucose, which enters the pathway. Ans: C Section: 16.1 32 Lactose intolerance is caused by a deficiency of A) lactase. B) elastase. C) lactose. D) sucrase. Ans: A Section: 16.1 33 How are the glycolytic enzymes regulated? A) transcriptional control B) reversible phosphorylation C) allosteric control Ans: D Section: 16.2 D) E) E) none of the above.

All of the above. None of the above.

34 The primary raw materials for gluconeogenesis are A) galactose and sucrose. D) B) pyruvate and oxaloacetate. E) C) lactate and alanine. Ans: C Section: 16.3

fructose and alanine. lactose and lactate.

35 How many high-energy phosphate bonds are expended in gluconeogenesis? A) three B) six C) two D) four E) one Ans: B Section: 16.3

Short-Answer Questions
36 What astounding discovery was made by the Buchners? Ans: They were the first to dispute Pasteurs assertion that fermentation required intact cells when they demonstrated that fermentation can occur in yeast extracts. Section: Introduction 37 Why do muscles need to generate ATP under aerobic and anaerobic conditions? Ans: Muscles initially function aerobically. However, when bursts of energy are required, the oxygen supply does not meet the demand. In order to generate sufficient ATP for energy demands during periods of extreme activity, the muscle depends on activity-dependent anaerobiosis. Section: Introduction 38 Both hexokinase and glucokinase phosphorylate glucose. The function of glucokinase is to phosphorylate glucose in liver cells as a means to regulate blood-sugar levels. Would you expect its Km to be higher or lower than hexokinase? Ans: Glucokinase must be responsive to elevated blood-glucose concentrations, thus it should have a higher Km. This lower binding affinity allows this enzyme to become more active at high glucose concentrations, which saturate hexokinase. Hexokinase serves to

Chapter 16 Glycolysis and Gluconeogenesis phosphorylate glucose (and other hexoses) in the cytosol, and has higher affinity for glucose, or a lower Km value. Section: 16.2 39 What two isomerization reactions occur in glycolysis? Why are these steps necessary? Ans: Glucose-6-phosphate is isomerized to fructose-6-phosphate, converting an aldose to a ketose, which then allows phosphorylation at the number 1 carbon. Later in the pathway, dihydroxyacetone-phosphate is converted to glyceraldehyde-3-phosphate, utilizing both of the molecules formed from fructose-1,6-bisphosphate cleavage. Section: 16.1 40 At equilibrium, there is far more DHAP than GAP. Yet the conversion of DHAP by triose phosphate isomerase proceeds readily. Why? Ans: The GAP formed is immediately removed by subsequent reactions, resulting in conversion of DHAP into GAP by the enzyme. Section: 16.1 41 How is the conversion of phosphoenolpyruvate to pyruvate accompanied by ATP formation? Ans: The enol phosphate possesses very high potential for phosphoryl transfer, which is due to the driving force of the tautamerization of the enol to the more stable ketone. Section: 16.1

42 Describe the biochemical explanation for galactosemia. Ans: Galactose is metabolized by conversion to Gal-1-P by galactokinase. The enzyme, galactose-1-phosphate uridyl transferase transfers a uridyl group from UDP-Glc to Gal-1P to produce UDP Gal. Then UDP-Gal is epimerized to UDP-Glc. UDP-galactose is a necessary intermediate in the metabolism of galactose. Individuals deficient in galactose1-phosphate uridyl transferase activity cannot metabolize galactose, which leads to elevated levels of galactose in the blood and urine. This genetic disease is referred to as galactosemia. Section: 16.1 43 Give the reactions by which glycerol (from fats) can be metabolized into pyruvate or synthesized into glucose. Ans: H+
CH2OH HO C H CH2OH glycerol ATP ADP CH2OH HO C H
-2

NAD

NADH

CH2OH O C CH2OPO3-2 dihydroxyacetone phosphate

Glycerol kinase

CH2OPO 3 glycerol phosphate

Glycerol phosphate dehydrogenase

After the glycerol is converted into DHAP, it is isomerized into GAP, which can then either proceed down glycolysis to pyruvate or up gluconeogenesis to glucose. Section: 16.3 44 How is glycolysis maintained under anaerobic conditions? Ans: Pyruvate can be reduced to either lactate or ethanol, and this reaction is accompanied by the oxidation of NADH to regenerate NAD+. Section: 16.1

Chapter 16 Glycolysis and Gluconeogenesis 45 How does citrate influence glycolysis? Ans: Phosphofructokinase is inhibited by citrate, which is an intermediate in the citric acid cycle. Thus, if citrate levels are high, the enzyme is inhibited, and fewer glucose molecules are metabolized. In this sense, citrate serves as a cell indicator. High levels of citrate in the cytoplasm means that biosynthetic precursors are abundant, and so there is no need to degrade additional glucose for this purpose. Section: 16.2

46 Why is it more sensible for phosphofructokinase to be an important control step, rather than hexokinase? Ans: Phosphofructokinase catalyzes the first committed step in the glycolytic pathway. At this point, the molecule is committed to entering the glycolytic path. In contrast, production of G6P is the first step in many different paths. Thus, glycolytic control would not be maintained by tight regulation of hexokinase. Section: 16.2 47 What two functions are attributed to substrate cycles? Ans: The substrate cycles regulate glycolytic path flux by amplifying metabolic signals and they generate body heat produced by the hydrolysis of ATP. Section: 16.4 48 Which metabolic steps differ from glycolysis in gluconeogenesis? Ans: There are three irreversible steps in glycolysis, which require four different steps in gluconeogenesis: pyruvate conversion to phosphoenolpyruvate via an oxaloacetate intermediate, fructose 1,6-bisphosphate hydrolysis, and the hydrolysis of glucose 6phosphate. Section: 16.3 49 How are gluconeogenesis and glycolysis regulated reciprocally? Ans: The enzymes involved in two substrate cycles are control points. Figure 16.28 in the text shows the glycolytic path activation by F-2,6-BP, AMP, and F-1,6-BP; whereas ATP, alanine, citrate, and protons inhibit glycolysis. Gluconeogenesis is activated by citrate and acetyl CoA and inhibited by F-2,6-BP, AMP, and ADP. Section: 16.4 50 Describe the two isoforms of lactate dehydrogenase. Ans: Two forms exist, called M and H, which predominate in skeletal and heart muscle, respectively. The two forms are products of different genes, but are similar in structure, and can form tetramers in various H:M ratios. The two forms differ in their sensitivity to pyruvate. H4 functions primarily to oxidize lactate to pyruvate, which serves as a fuel for aerobic metabolism. In contrast, M4 produces lactate so that glycolysis can continue under anaerobic conditions. Section: 16.4