Glycolysis Flashcards
The transport of glucose from the blood into the cell in mammalian tissues occurs on a specific but passive transporter. Why is active transport not required for glucose utilization by most cells?
The liver functions to maintain the blood glucose levels at 4 to 5 mM and thus maintains a concentration gradient favorable for the movement of glucose into cells. Phosphorylation of the glucose by hexokinase in the cell ensures that the free (non-phosphorylated) glucose concentration inside the cell is kept at very low levels, thus maintaining the gradient.
Why is the 6-phosphofructo-1-kinase (PFK1) reaction rather than the hexokinase reaction considered the commitment step for glycolysis?
While the phosphorylation of glucose by hexokinase insures that the glucose can be utilized by the cell, in many tissues the G-6-P produced may be consumed in the synthesis of glycogen or in the hexose monophosphate pathway. PFK1 catalyzes the first irreversible reaction that is unique to the glycolytic pathway.
What are the coupled reactions/enzymes in the first substrate-level phosphorylation of glycolysis? What is the common intermediate?
The enzymes: glyceraldehyde 3-phosphate dehydrogenase and 3-phosphoglycerate kinase The common intermediate: 1,3 bisphosphoglycerate. The reaction: The dehydrogenase catalyzes the reversible oxidation of the glyceraldehyde-3-phosphate; NAD+ is the coenzyme-cosubstrate. The second reaction involves the reversible transfer of the phosphate from the carboxyl group of the bisphosphoglycerate to ADP to give rise to ATP.
What are the coupled reactions/enzymes in the second substrate-level phosphorylation? What is the common intermediate?
The enzymes: enolase and pyruvate kinase; The common intermediate: phosphoenolpyruvate The reaction: The second of the two substrate-level phosphorylations involves the formation of phosphoenolpyruvate (PEP) from 2-phosphoglycerate by the loss of H2O. This is catalyzed by the enzyme, enolase. The phosphate of PEP is transferred to ADP by the enzyme, pyruvate kinase (PK).
In a myocardial infarction (MI), the blood supply to a portion of the heart is cut off and anaerobic glycolysis occurs, producing lactate. In the oxidation of glucose to lactate, what is the net yield of ATP for each glucose consumed?
With 2 ATP utilized (phosphorylation reactions) and 4 ATP produced per glucose molecule (3- phosphoglycerate kinase and pyruvate kinase reactions), the net yield in anaerobic glycolysis is 2 ATP.
Why is ATP production decreased in PK deficiency? Why might ATP synthesis from the glyceraldehyde-3-phosphate dehydrogenase/3-phosphoglycerate kinase reaction be inhibited also?
PK catalyzes one of the ATP-producing reactions of glycolysis. [Note that any enzymopathy of glycolysis would result in decreased ATP production.] PK deficiency decreases pyruvate production. Consequently, the LDH-catalyzed reoxidation to NAD+ of the NADH produced in the glyceraldehyde 3-phosphate dehydrogenase step is inhibited—pyruvate is the substrate of LDH. The resulting rise in the NADH to NAD+ ratio inhibits glycolysis. [Note: RBCs lack mitochondria and LDH is their only means of reoxidizing NADH.]
Why are RBC especially vulnerable to a reduction in ATP from glycolysis?
RBC lack mitochondria and so pyruvate is reduced to lactate (anerobic glycolysis) which enters the plasma. RBC therefore are unable to completely oxidize glucose to CO2 + H2O, and so are dependent on glycolysis for ATP (net 2 ATP/glucose) production.
With PK deficiency, levels of 2,3-bisphosphoglycerate (2,3 BPG) may increase up to three-fold. Explain
With any enzyme deficiency, there is a build-up of substrate and a decrease in product. The substrate that accumulates can convert relatively minor pathways into major ones. In PK deficiency, PEP accumulates. Because enolase, phosphoglycerate mutase, and 3-phosphoglycerate kinase catalyze reversible reactions, the increase in PEP results in an increase in 1,3 bisphosphoglycerate. In RBC, the 1,3 bisphosphoglycerate can be converted to 2,3 bisphosphoglycerate (2,3-BPG) by the action of a mutase. We will see that 2,3-BPG increases O2-delivery by RBCs.
All of the following enzymes are involved in aerobic glycolysis EXCEPT: A. phosphoglucose isomerase B. 6-phosphofructo-1-kinase C. aldolase D. 3-phosphoglycerate kinase E. lactate dehydrogenase
Answer: E. Lactate dehydrogenase is only involved in anaerobic glycolysis.
All of the following are obligatory intermediates in glycolysis EXCEPT: A. glucose-6-phosphate B. glucose-1-phosphate C. fructose-6-phosphate D. fructose-1,6-bisphosphate E. glyceraldehyde 3-phosphate
Answer: B. In glycogenolysis, gucose-1-phosphate is the direct product of the reaction in which glycogen phosphorylase cleaves off a molecule of glucose from a greater glycogen structure
All of the following glycolytic enzymes catalyze irreversible reactions EXCEPT: A. glucokinase B. hexokinase C. 6-phosphofructo-1-kinase (PFK1) D. 3-phosphoglycerate kinase E. pyruvate kinase
Answer: D. The second reaction of the first step of substrate level phosphorylation involves the reversible transfer of the phosphate from the carboxyl group of the bisphosphoglycerate to ADP to give rise to ATP. The enzyme involved is 3-phosphoglycerate kinase. The name actually describes the reverse reaction and, indeed, in this case the reaction is freely reversible.
A substrate for the enzyme aldolase is A. glucose-1-phosphate B. glucose-6-phosphate C. fructose-6-phosphate D. fructose-1,6-bisphosphate E. 2-phosphoglycerate
Answer: D. F-1,6-P is subsequently split into two triose phosphates, dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP), by the enzyme, aldolase.
Identify which of the glycolytic intermediates listed below has a ∆G°′ of hydrolysis more negative than -7 kcal/mol. A. glucose-6-phosphate B. fructose-1,6-bisphosphate C. 3-phosphoglycerate D. 2-phosphoglycerate E. 2-phosphoenolpyruvate
Answer: E. Phosphoenolpyruvate has one of the highest high-energy bonds.
The oxidation of a mole of glucose to lactate generates a net of A. 1 mole of ATP B. 2 moles of ATP C. 3 mole of ATP D. 4 moles of ATP E. 5 moles of ATP
Answer: B. With 2 ATP utilized (phosphorylation reactions) and 4 ATP produced per glucose molecule (3- phosphoglycerate kinase and pyruvate kinase reactions), the net yield in anaerobic glycolysis is 2 ATP.
The ATP generated in glycolysis arise from substrate level phosphorylation (SLP). Which of the following about SLP is true? A. occurs only in mitochondria B. requires molecular oxygen (O2) C. is a single-step process D. involves a high-energy common intermediate
Answer: D. The second of the two substrate-level phosphorylations involves the formation of phosphoenolpyruvate (PEP) from 2-phosphoglycerate by the loss of H2O. This is catalyzed by the enzyme, enolase. The hydrolysis of the phosphate group of PEP has ∆G°′ of more than -14 kcal/mole.
