Gluconeogenesis

Question 1

Gluconeogenesis

Answer 1

• important to maintain blood glucose levels during fasting or starvation
• LIVER!!!: synthesis of new glucose from non-carb precursors

Question 2

Can mammals convert FA to sugars?

Answer 2

WE CANNOT MAKE GLUCOSE FROM FA!

Question 3

Gluconeogenesis requires:

Answer 3

• source of energy

- source of carbons for the backbone of glucose

Question 4

Carbon skeletons are provided for gluconeogenesis from 3 sources:

Answer 4

1. lactate: produced in tissues such as RBCs and exercising muslces
2. glucogenic amino acids: (i.e. alanine) derived from muscle protein
3. glycerol: released from TAGs during lipolysis in adipose tissue GLYCEROL BACKBONE NOT FA CHAINS!

Question 5

Energy for gluconeogenesis is provided by

Answer 5

metabolism of FA released from adipose tissue

Question 6

2 ketogenic AA that can’t undergo Gluconeogenesis

Answer 6

Leucine and Lysine

Question 7

Where is gluconeogenesis done

Answer 7

mostly in the LIVER, a little in the kidney

NOT IN THE MUSCLE!

Question 8

Metabolism in the Cytosol

Answer 8

• glycolysis
• pentose phosphate pathway
• fatty acid synthesis

Question 9

Metabolism in the Mitochondrial Matrix

Answer 9

• TCA Cycle
• oxidative phosphorylation
• B-oxidation of FA
• ketone body formation

Question 10

Metabolism in BOTH the cytosol and mitochondrial matrix

Answer 10

• gluconeogenesis

- urea synthesis

Question 11

Gluconeogenesis vs. Glycolysis

Answer 11

Glycolysis: occurs in all tissues, esp the muscle and brain

Gluconeogenesis: occurs mainly in the liver and a little in the kidney

** [substrate] determines directionality **

Question 12

Gluconeogenesis donors

Answer 12

lactate (-> pyruvate)
alanine (-> pyruvate)
glycerol backbone (-> dihydroxyacetone)

Question 13

3 regulated steps of glycolysis

Answer 13

1. Hexokinase/Glucokinase
2. PFK I
3. Pyruvate kinase
   - all require ATP

must be BYPASSED in gluconeogenesis

Question 14

Bypass of Pyruvate Kinase

Answer 14

1. Pyruvate carboxylase (mitochondria)
2. Phosphoenol pyruvate carboxykinase (PEPCK) (cytoplasm and mitochondria)

ENERGY REQUIRING
- add a C then remove a C to drive unfavorable reactions forward

Question 15

Bypass of PFK-I

Answer 15

Fructose 1,6-bisphosphatase-1 (cytoplasm)

Question 16

Bypass of Hexokinase/Glucokinase

Answer 16

Glucose 6-phosphatase (ER)

Question 17

Carboxylases ABC

Answer 17

ATP
Biotin
CO2

Question 18

Pyruvate Carboxylase; Pyruvate Carboxykinase (PEPCK)

Answer 18

Pyruvate -> OAA
- either converted in mitochondria to PEP, or transferred out of mitochondria to cytosol via malate shuttle which is then converted to OAA and PEP

WHICH PATHWAY IS DEPENDENT ON NADH LEVELS

• if lactate is precursor, NADH is present in cytosol so OAA-> PEP in mitochondria
• if pyruvate is precursor, NADH has to be moved to cytosol via shuttle

Question 19

Malate Shuttle

Answer 19

pyruvate -> OAA -> malate -> OAA -> PEP
uses and produces NADH

• without shuttle, cytosolic NADH concentrations would become limiting

Question 20

PEPCK regulation

Answer 20

Glucagon increases transcription of the gene for PEPCK during fasting
- uses CRE and CREB