Glycolysis/ Gluconeogenesis

Question 1

Substrate Level Phosphorylation

Answer 1

Metabolic reaction that results in the formation of ATP or GTP)] by the direct transfer and donation of a phosphoryl (PO3) group from a phosphorylated reactive intermediate.

Normally ATP is formed by Oxidative Phosphorylation

Question 2

Aldolase

Answer 2

Aldolase A in muscle, B in the liver

cleaves fructose 1,6 bisphosphate to two trioses:
glyceraldehyde 3 phosphate and dihydroxyacetone phosphate. (reverseable)

Question 3

Triosephosphate isomerase

Answer 3

converts dihydroxyacetone phosphate to glyceraldehyde 3 phosphate (reversable)

Question 4

Arsenate

Answer 4

Replaces inorganic phosphate in the step of glycolysis that produces 1,3-bisphosphoglycerate This yields 1-arseno-3-phosphoglycerate instead, it quickly hydrolyzes, forming, 3-phosphoglycerate. Therefore glycolysis proceeds, but the ATP is lost - arsenate is an uncoupler of glycolysis

Can also inhibit the conversion of pyruvate into acetyl-CoA, blocking the Krebs cycle and therefore resulting in further loss of ATP

Question 5

Fluoride

Answer 5

inhibits the activity of enolase in the reversable reaction of 2-phosphoglycerate to phosphenolpyruvate

Question 6

Pyruvate Kinase

Answer 6

catalyzes the transfer of a phosphate group from phosphoenolpyruvate to ADP, yielding one molecule of pyruvate and one molecule of ATP. (Irreversable)

Inhibited by ATP and alanine
activated by F1,6 BisP

Phosphorylation of PK inhibits glycolysis

Question 7

Irreversible reactions of Glycolysis

Answer 7

Glucose to Glucose 6 Phosphate via Hexokinase

Fructose 6 Phosphate to Fructose 1,6 Bisphosphate via PFK1

Phosphoenolpyruvate to Pyruvate via pyruvate kinase

Question 8

Substrate Level Phosphorylation steps in Glycolysis

Answer 8

1,3 Bisphosphoglycerate to 3 phosphoglycerate
using phosphoglycerate kinase

Phosphoenolpyruvate to Pyruvate
using pyruvate kinase

Question 9

Fates of Pyruvate

Answer 9

Aerobic (Oxygen and Mitochondria): formation of Acetyl CoA, enter TCA Cycle

Anerobic: Formation of Lactate, goes to liver via Cori Cycle

Question 10

Glucokinase

Answer 10

In Liver and b-cells of pancreas

Forms glucose 6 phosphate from Glucose.

Requires ATP

Genetic deficiency can lead to maturity onset diabetes of the young Type 2 (MODY 2)

In the b-cells, glucokinaseis involved with the recognition of high blood glucose levels leading to insulin release

“stored” in the nucleus at high fructose 6-P levels and is transported back into the cytosolat high free glucose levels

Question 11

Phosphoglucose Isomerase

Answer 11

Glucose 6 phosphate to fructose 6 phosphate

Question 12

Phosphofructokinase 1 (PFK 1)

Answer 12

PFK-1 catalyzes the important “committed” step of glycolysis, the conversion of fructose 6-phosphate and ATP to fructose 1,6-bisphosphate and ADP

key regulatory and rate limiting steps of glycolysis

PFK-1 is inhibited by physiological ATP levels (when the objective to generate ATP is achieved) and by Citrate

(Citrate has to be in the cytosol which can happen during fatty acid de novo synthesis [liver]).

Question 13

Glyceraldehyde 3 phosphate dehydrogenase

Answer 13

Catalyses the conversion of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate. Forms NADH that is transported to the mitochondria for ATP synthesis

Question 14

Phosphoglycerate Kinase

Answer 14

catalyzes the reversible transfer of a phosphate group from 1,3-bisphosphoglycerate (1,3-BPG) to ADP producing 3-phosphoglycerate (3-PG) and ATP.

Question 15

Phosphoglycerate Mutase

Answer 15

Catalyzes the internal transfer of a phosphate group from C-3 to C-2 which results in the conversion of 3-phosphoglycerate to 2-phosphoglycerate

Question 16

Enolase

Answer 16

conversion of 2-phosphoglycerate to phosphoenolpyruvate

Question 17

Lactate dehydrogenase

Answer 17

catalyzes the interconversion of pyruvate and lactate with concomitant interconversion of NADH and NAD+. It converts pyruvate, the final product of glycolysis, to lactate when oxygen is absent or in short supply, and it performs the reverse reaction during the Cori cycle in the liver

Question 18

Energetics of aerobic glycolysis

Answer 18

Glucose→2 Pyruvate
•2 NADH+ H+(formed in glyceraldehyde3 phosphate dehydrogenasereaction) = 2x3 = 6ATP

• 4 ATP (formed in the substrate level phosphorylationreactions) (2ATP from each mol of glyceraldehyde3 phosphate)
• -2ATP used in the energy investment phase
• Total = 8 ATP (Aerobic glycolysis)

Question 19

Energeticsof anaerobic glycolysis

Answer 19

Glucose→2 Lactate
•2 NADH+ H+(formed in glyceraldehyde3 phosphate dehydrogenasereaction) are used in lactate dehydrogenasereaction

• 4 ATP (formed in the substrate level phosphorylationreactions) (2ATP from each mol of glyceraldehyde3 phosphate)
• -2ATP used in the energy investment phase
• Total = 2 ATP (Anaerobic glycolysis)

Question 20

Lactate Dehydrogenase

Answer 20

Forms Latate and NAD+ from NADH and Pyruvate

Reversible reaction.

Question 21

Pyruvate Carboxylase

Answer 21

Converts Pyruvate to Oxaloacetate. Requires CO2 and ATP

biotin required as a coenzyme

First step in gluconeogenesis

Question 22

Phosphoenolpyruvate Carboxykinase

Answer 22

Gluconeogenesis

Converts Oxaloacetate to PEP and CO2.

Requires GTP

Question 23

Fructose 1,6 bisphosphatase

Answer 23

Converts Fructose 1,6 Bisphosphateand ATP to fructose 6 phosphate and ADP in gluconeogenesis.

primary regulator of gluconeogenesis

Question 24

Glucose 6 phosphatase

Answer 24

Converts glucose 6 phosphate and ATP to glucose and ADP in gluconeogenesis

Question 25

Fructose 2,6 bisphosphate

Answer 25

Created from fructose 1,6 bisphosphate by PFK2 and activates glycolysis steps that are otherwise inhibited by ATP

Question 26

Purpose of glycolysis in the liver

Answer 26

Reduce blood glucose levels. (The liver already has enough ATP)

Question 27

Allosteric regulation of pyruvate kinase

Answer 27

PK is feed-forward activated by F1,6-bisP formed in the liver, RBC and proliferating cells.

PK is feed-back inhibited by ATP which is now overcome by fructose 1,6-bisP in these cells

not found in muscle, heart, and brain.

Question 28

Insulin

Answer 28

dephosphrylates, induces glycolysis and energy production

Question 29

Glucagon

Answer 29

Phosphorylates, inhibits glycolysis, induces gluconeogenesis and energy storage

Question 30

Glycerol in gluconeogenesis

Answer 30

Glycerol from the blood is phosphorylated and in the presence of NAD+ is converted to dihydroxyacetone phosphate.

Question 31

Energy source for gluconeogenesis

Answer 31

Gluconeogenesis and degradation of fatty acids take place in the liver at the same time.

The b-oxidation of fatty acids generates FADH2 and NADH and leads eventual to ATP formation in the ETC and oxidative phosphorylation