Biochem - Metabolism (Gluconeogenesis & HMP shunt)

Question 1

What are 4 important irreversible enzymes in gluconeogenesis?

Answer 1

(1) Pyruvate carboxylase (2) Phosphoenolpyruvate carboxykinase (3) Fructose-1,6-bisphosphatase (4) Glucose-6-phosphatase; Think: “Pathway Produces Fresh Glucose”

Question 2

Where is Pyruvate carboxylase found? What reaction does it catalyze?

Answer 2

In mitochondria. Pyruvate => Oxaloacetate

Question 3

Where is Phosphoenolpyruvate carboxylase found? What reaction does it catalyze?

Answer 3

In cytosol. Oxaloacetate => Phosphoenolpyruvate

Question 4

Where is Fructose-1,6-biphosphatase found? What reaction does it catalyze?

Answer 4

In cytosol. Fructose-1,6-BP => Fructose-6-P

Question 5

Where is Glucose-6-phosphatase found? What reaction does it catalyze?

Answer 5

In ER. Glucose-6-P => Glucose

Question 6

What 2 factors are required for Pyruvate Carboxylase activity? What activates Pyruvate Carboxylase?

Answer 6

Requires biotin, ATP. Activated by acetyl-CoA.

Question 7

What factor is required for Phosphoenolpyruvate carboxykinase?

Answer 7

Requires GTP

Question 8

What is a positive versus negative regulator of Fructose-1,6-bisphosphatase?

Answer 8

POSITIVE: Citrate; NEGATIVE: Fructose-2,6-biphosphate

Question 9

Where does gluconeogenesis primarily occur? What is its purpose?

Answer 9

Occurs primarily in liver; serves to maintain euglycemia during fasting.

Question 10

Besides liver, where are gluconeogenesis enzymes also found?

Answer 10

Enzyme also found in kidney, intestinal epithelium.

Question 11

What results from a deficiency of key gluconeogenic enzymes?

Answer 11

Deficiency of the key gluconeogenic enzymes cause hypoglycemia.

Question 12

What keeps muscle from participating in gluconeogenesis?

Answer 12

Muscle cannot participate in gluconeogenesis because its lacks glucose-6-phosphatase

Question 13

What do odd-chain fatty acids yield during metabolism? What are the potential metabolic uses of this product?

Answer 13

Odd-chain fatty acids yield 1 propionyl-CoA during metabolism, which can enter the TCA cycle (as succinyl-CoA), undergo gluconeogenesis, and serve as a glucose source

Question 14

What is the metabolic limitation of even-chain fatty acids, and what causes this?

Answer 14

Even-chain fatty acids cannot produce new glucose, since they yield only acetyl-CoA equivalents.

Question 15

What are 2 metabolic benefits of the HMP shunt?

Answer 15

(1) Provides a source of NADPH from abundantly available glucose-6-P (NADPH is required for reductive reactions, e.g., glutathione reduction inside RBCs, fatty acid and cholesterol biosynthesis). Additionally, this pathway yields (2) ribose for nucleotide synthesis and glycolytic intermediates.

Question 16

What is another name for the HMP shunt?

Answer 16

HMP shunt (pentose phosphate pathway)

Question 17

In brief, how does the HMP shunt yield NADPH? For what type of reactions is NADPH required? Give 3 examples of such reactions.

Answer 17

Provides a source of NADPH from abundantly available glucose-6-P (NADPH is required for reductive reactions, e.g., glutathione reduction inside RBCs, fatty acid and cholesterol biosynthesis)

Question 18

What sugar does the HMP shunt yield? What are 2 of its metabolic uses?

Answer 18

Ribose for nucleotide synthesis and glycolytic intermediates.

Question 19

What are the phases of HMP shunt, and where do they occur?

Answer 19

2 distinct phases (oxidative and nonoxidative), both of which occur in the cytoplasm

Question 20

How much ATP is used versus produced by the HMP shunt?

Answer 20

No ATP is used or produced

Question 21

What are 4 sites where HMP shunt (pentose phosphate pathway) takes place?

Answer 21

Sites: (1) Lactating mammary glands (2) Liver (3) Adrenal cortex (sites of fatty acid or steroid synthesis) (4) RBCs

Question 22

Of the phases of HMP shunt, which is reversible versus irreversible?

Answer 22

(1) Oxidative (irreversible) (2) Nonoxidative (reversible)

Question 23

What are the key substrate and enzyme(s) of the oxidative (irreversible) phase of the HMP shunt? What are the products of this phase?

Answer 23

SUBSTRATE: Glucose-6-Pi; ENZYME: Glucose-6-P dehydrogenase; PRODUCTS: CO2, 2 NADPH, Ribulose-5-Pi

Question 24

What area the key substrate and enzyme(s) of the nonoxidative (reversible) phase of the HMP shunt? What are the products of this phase?

Answer 24

SUBSTRATE: Ribulose-5-Pi; ENZYME: Phosphopentose isomerase, Transketolases; PRODUCTS: Ribose-5-Pi, G3P, F6P

Question 25

Which HMP shunt phase reaction is the rate-limiting step? What enzyme(s) is (are) catalyze this step?

Answer 25

Oxidative (irrversible); Glucose-6-P dehydrogenase converts Glucose-6-Pi into CO2 + 2 NADPH + Ribulose-5 Pi

Question 26

What cofactor is required by the nonoxidative (reversible) reaction of HMP shunt? What enzyme(s) catalyze(s) this?

Answer 26

Requires B1; Phosphopentose isomerase, Transketolases convert Ribulose-5-Pi into Ribose-5-Pi + G3P + F6P