Chapter 13: Gluconeogenesis

Question 1

Gluconeogenesis defined

Answer 1

• Synthesis of new glucose from non-carbohydrate sources

Question 2

Gluconeogenesis occurs in

Answer 2

• Primarily in the liver

- Also in the kidney cortex

Question 3

When liver glycogen is depleted

Answer 3

• Gluconeogenesis makes glucose available for the brain and RBCs

Question 4

ATP input required by gluconeogenesis

Answer 4

• Requires 6 ATP input

- Largely from beta oxidation of fatty acids

Question 5

Mobilization of fats

Answer 5

• Used in making ATP

Question 6

Gluconeogenic substrates

Answer 6

• First converted to oxaloacetate

Question 7

Pyruvate carboxylase (only in mitochondria)

Answer 7

• Converts pyruvate to oxaloacetate in order to bypass

Question 8

Major non-carbohydrate substrates for gluconeogenesis first converted to oxaloacetate

Answer 8

• Amino acids (ala/glu)
• CAC intermediates
• Glycolytic intermediates (Pyruvate, PEP)
• Lactate
• Glycerol

Question 9

Breakdown products of fatty acids, Acetyl-SCoA, and acetate

Answer 9

• No net synthesis of oxaloacetate from the breakdown of these products

Question 10

Solely ketogenic amino acid residues

Answer 10

• Leucine

- Lysine

Question 11

Hormone-sensitive lipase

Answer 11

• Mobilizes gluconeogenesis from glycerol originating from stored triacylglycerides

Question 12

Mobilization of gluconeogenesis from triacylglycerides requires

Answer 12

• Glycerol kinase

- Glycerol-3-phosphate dehydrogenase

Question 13

All reactions in gluconeogenesis

Answer 13

• All are irreversible and exergonic (spontaneous)

Question 14

3 irreversible steps in glycolysis that must be bypassed during gluconeogenesis

Answer 14

• Pyruvate kinase (PEP –> pyruvate)
• PFK-1 (F-6-P –> F-1,6-Bp)
• Hexokinase (glucose –> G-6-P)

Question 15

Mitochondrial pyruvate carboxyalse

Answer 15

• Converts pyruvate to oxaloacetate

- Anaplerotic reaction

Question 16

Oxaloacetate exits the mitochondria as either

Answer 16

• Aspartate (route 1)

- Malate (route 2)

Question 17

Outside the mitochondria

Answer 17

• Oxaloacetate can continue in gluconeogenesis

- Cytoplasmic PEPCK

Question 18

Mitochondrial PEPCK

Answer 18

• Converts oxaloacetate to PEP

- PEP can then exit the mitochondria directly through a translocase

Question 19

Malate dehydrogenase

Answer 19

• Uses up NAD
• Generates NADH
• Consequences for glycolytic pathway which will need NAD

Question 20

Anaplerotic reaction

Answer 20

• Topping off reaction
• OAA is an intermediate
• No depleting of the TCA intermediate
• So it doesn’t want to let OAA go
• Have to convert it via MDH or aspartate aminotransferserase

Question 21

Pyruvate kinase is irreversible

Answer 21

• Pyruvate cannot be converted to PEP by reversing this enzyme

Question 22

Fat is converted to Acetyl Co A

Answer 22

• Required for gluconeogenesis (everything is connected)

Question 23

Pyruvate carboxylase

Answer 23

• Anaplerotic reaction
• Converts pyruvate to oxaloacetate (exits the mitochondria as malate or aspartate)
• Solely in mitochondria
• Allosteric and biotin-dependent
• Requires Acetyl-SCoA as an obligate allosteric activator

Question 24

PEP carboxykinase

Answer 24

• Decarboxylation and phosphorylation of oxaloacetate to PEP

- Both cytoplasmic and mitochondrial in humans

Question 25

PEP carboxykinase is over expressed in

Answer 25

- Diabetes | - Leads to hyperglycemia

Question 26

If diabetic and not in the starving state

Answer 26

- Glucose is still being made

Question 27

Mitochondrial pyruvate carboxylase

Answer 27

- Forms OAA from pyruvate

Question 28

NAHD-linked mitochondrial MDH

Answer 28

- Converts OAA to malate

Question 29

Cytosolic MDH

Answer 29

- Reoxidizes malate in the cytosol to OAA

Question 30

OAA is decarboxylated and phosphorylated in the cytoplasm by

Answer 30

- PEP carboxykinase

Question 31

PEP in the cytosol

Answer 31

- Can by converted to fructose-1,6,-bisphosphate by glycolytic enzymes operating in reverse

Question 32

If the cell needs energy

Answer 32

- Glycolytic pathway is favored and gluconeogenesis is inhibited

Question 33

PFK-1 is irreversible and must be bypassed

Answer 33

- Bypass reaction is catalyzed by fructose-1,6-bisphosphate - Stimulated by citrate - Inhibited by AMP

Question 34

Hexokinase is irreversible and must be bypassed

Answer 34

- Reaction is bypassed by a membrane-bound glucose-6-phosphatase

Question 35

With high km of glucokinase in the liver

Answer 35

- Most glucose will not be phosphorylated and thus exit into circulation

Question 36

Glucose-6-phosphatase

Answer 36

- ER membrane bound enzyme | - Enzyme is absent from muscle tissue

Question 37

Glucose-6-phosphatase absent from muscle tissue

Answer 37

- Causes muscle to use gluconeogenic enzymes to replenish glycogen not maintain BSL

Question 38

Endoplasmic reticulum proteins

Answer 38

- Assist in the formation of glucose | - From cytosolic G-6-P

Question 39

Alcohol oxidation

Answer 39

- Primarily in liver (major site of gluconeogenesis)

Question 40

Alcohol metabolism

Answer 40

- Reduces gluconeogenesis | - Requires NAD+ or produces NADH

Question 41

Cytosolic alcohol dehydrogenase

Answer 41

- Metabolizes ethanol to acetaldehyde

Question 42

Mitochondrial acetaldehyde dehydrogenase

Answer 42

- Converts acetaldehyde to acetate - Then to Acetyl-SCoA - Then metabolized to CO2 and H2O

Question 43

Alcohol metabolism shifts

Answer 43

- Shifts equilibrium of cytosolic lactate dehydrogenase from pyruvate formation to lactate synthesis

Question 44

Alcohol metabolism favors

Answer 44

- Reduction of oxaloacetate to malate by cytosolic MDH

Question 45

Reduction of oxaloacetate to malate

Answer 45

- Reduces OAA availability for gluconeogenesis

Question 46

Increasing NADH results in

Answer 46

- Decrease in gluconeogenesis | - Leads to hypoglycemia

Question 47

Use of NAD+ by alcohol metabolism

Answer 47

- Impairs metabolism of pyruvate, urates, and fatty acids - Reduces gluconeogenesis - Leads to alcohol-induced hyperglycemia

Question 48

Alcohol-induced hyperglycemia

Answer 48

- Affects the brain | - Causes a drop in body temperature

Question 49

Defective gluconeogenic activity

Answer 49

- Prevents lactate | - Leads to lactic acidosis and fasting hypoglycemia

Question 50

Under normal circumstances, in mature red blood cells (lacking mitochondria), and exercising muscle (under anaerobic conditions)

Answer 50

- The pyruvate end product of glycolysis is converted to lactate by lactate dehydrogenase

Question 51

Lactate formation

Answer 51

- Reversible, but favored under physiological conditions

Question 52

The Cori Cycle

Answer 52

- Lactate can diffuse out of the muscle cell - Can be converted to glucose in the liver - Cycle occurs in muscle and red blood cells

Question 53

Gluconeogenesis uses

Answer 53

- Lactate | - Pyruvate

Question 54

Gluconeogenesis primarily uses C-skeletons of

Answer 54

- Alanine | - Glutamate

Question 55

Gluconeogenesis is essential for maintaining

Answer 55

- Blood sugar levels

Question 56

Mobilization of gluconeogenesis from triacylglycerides produces

Answer 56

- Dihydroxyacetone phosphate/DHAP (glycolytic intermediate)

Question 57

PEP carboxykinase synthesis is repressed by

Answer 57

- High glucose diets, but elevated in diabetes mellitus