Glycolysis, TCA Cycle, and Oxidative Phosphorylation

Question 1

GLUT4

Answer 1

Transports glucose into skeletal muscle and adipose tissue

Up-regulated by exposure to insulin

Question 2

GLUT2

Answer 2

Transports glucose into hepatocytes

Not insulin sensitive

Question 3

Hexokinase

Answer 3

Pathway: Glycolysis

Catalyzes the first phosphorylation of glucose in most body cells; this reaction is irreversible

Hexokinase is not very selective but has a low Km for sugars

Question 4

Glucokinase

Answer 4

Pathway: Glycolysis

Catalyzes the first phosphorylation of glucose in hepatocytes and pancreatic B-cells; this reaction is irreversible

Highly selective for glucose but has a high Km; therefore acts as a ‘glucose sensor’ that is highly active when cellular glucose is high, and is less active when cellular glucose is low, allowing glucose efflux from the cell under these conditions

Question 5

Phosphofructokinase 1 (PFK1)

Answer 5

Pathway: Glycolysis

Catalyzes the phosphorylation of Fructose-6-Phosphate to Fructose-1,6-Bisphosphate

This is the major rate limiting and regulatory step of glycolysis

PFK1 is activated by AMP and F-2,6BP
PFK is inhibited by ATP and citrate

Question 6

Phosphofructokinase 2 (PFK2)

Answer 6

Pathway: Glycolysis

Converts Fructose-6-Phosphate to Fructose-2,6-Bisphosphate, a strong activator of PFK1

Question 7

Glyceraldehyde-3-Phosphate Dehydrogenase

Answer 7

Pathway: Glycolysis

Catalyzes the phosphorylation of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate

Generates 2 NADH

Question 8

Phosphoglycerate Kinase

Answer 8

Pathway: Glycolysis

Catalyzes the phosphorylation of 2ADP by 1,3-bisphosphoglycerate, yielding 2 ATP (net ATP is 0)

Question 9

Pyruvate Kinase

Answer 9

Pathway: Glycolysis

Catalyzes the phosphorylation of 2ADP by 2PEP, yielding 2 ATP (net ATP is 2)

Question 10

Which cell types undergo anaerobic regeneration of NAD+ during glycolysis?

Answer 10

RBCs
Sperm
Retina

Question 11

Pyruvate dehydrogenase

Answer 11

Enzymatic link between glycolysis and TCA cycle; converts pyruvate to acetylcoA in the mitochondrial matrix

Requires thiamine (B1), riboflavin (B2), and niacin

PDH is allosterically activated by AMP and NAD+; it is inhibited by ATP and NADH

PDH is active in the fed state (high insulin, dephosphorylated) and is inhibited in the fasting state (high glucagon, phosphorylated)

Question 12

Citrate Synthase

Answer 12

Pathway: TCA Cycle

Catalyzes the condensation between oxaloacetate and acetylcoA to yield citrate

High citrate reflects high flux through the TCA cycle and feedback inhibits PFK1

Citrate can leave the TCA cycle to form fatty acids via lipogenesis

Question 13

a-ketoglutarate

Answer 13

Intermediate of the TCA Cycle; production of a-ketoglutarate yields CO2 and NADH

Question 14

succinyl CoA

Answer 14

Production of succinyl coA from a-ketoglutarate yields a second molecule of CO2 and NADH

Question 15

Succinate dehydrogenase

Answer 15

Catalyzes the conversion of succinate to fumarate; enzyme-bound FAD is the electron acceptor and electrons from FADH2 are directly passed to coQ in the electron transport system

Question 16

Fumarase

Answer 16

Pathway: TCA Cycle

Catalyzes the conversion of fumarate to malate

Question 17

Malate dehydrogenase

Answer 17

Pathway: TCA Cycle

Catalyzes the conversion of malate to oxaloacetate; produces 3rd equivalent of NADH

Question 18

PGC1a

Answer 18

Molecular mediator of mitochondrial proliferation; being investigated as a drug target to increase oxidative capacity of muscle cells and therefore prevent metabolic diseases

Question 19

Sirtuins

Answer 19

SIR2 enzyme improves mitochondrial function and may be associated with decreased cellular oxidative damage and increased cellular longevity

Resveratrol found in red wine activates Sirtuins

Question 20

Lactate Dehydrogenase

Answer 20

Pathway: Gluconeogenesis

Interconverts lactate and pyruvate

Question 21

Pyruvate carboxylase

Answer 21

Pathway: Gluconeogenesis

Converts pyruvate to oxaloacetate within liver cell mitochondria

Question 22

Malate dehydrogenase

Answer 22

Pathway: Gluconeogenesis

Occurs as 2 isoforms; cytosolic enzyme converts oxaloacetate to malate, which leaves the mitochondria to enter the cytosol; cytosolic isoform regenerates oxaloacetate from malate

Question 23

Fructose-1,6-Bisphosphatase

Answer 23

Pathway: Gluconeogenesis

Part of the ‘bifunctional’ enzyme complex (PFK/F-1,6-Bisphosphatase)

High glucagon activates PKA, which phosphorylates PFK-2, inactivating it and leading to reduced production of F-2,6-BP; lower F-2,6-BP levels releases the inhibition of fructose-1,6-bisphosphatase, stimulating gluconeogenesis

Question 24

Glucose-6-Phosphatase

Answer 24

Pathway: Gluconeogenesis

Catalyzes the conversion of G-6-P to glucose in the final step of gluconeogenesis

G-6-P Phosphatase is found in hepatocytes and kidney cells; these are the only tissues that may export gluconeogenesis-produced glucose into the blood stream