Gluconeogenesis

Question 1

Glucose production

Answer 1

Only in liver and kidney
Glucose always required
- obligate energy source (ex RBC, sperm)
- needed to use fatty acids or ketones

BGL stays stable between meals or during fast

• glycogenolysis
• gluconeogenesis

Question 2

Glycogen overview

Answer 2

Storage of glucose
Liver -> circulation (maintain BGL)
Muscle -> own metabolism (can’t export)

Branched -> rapid degradation
Glycogenin = core -> + UTP glucose

Question 3

Glycogen synthesis

Answer 3

Glycogenin = core + autocatalytic enzyme
- adds 8 glucose to Tyr

Addition - requires UTP -> UDP-glucose
Glycogen synthase:
 -  adds UDP glucose via a1-4
(+) G6P
Branching enzyme:
 - transferes a1-4 to a1-6

Question 4

Glycogenolysis

Answer 4

Glycogen phosphorylase
a1-4 + Pi -> G1P
- requires pyridoxal6P (Vit B6)

Debranching enzyme

• transfers 3 to another chain
• removes 1 glucose (not phosphorylated)

Question 5

Liver glucose export

Answer 5

Exclusive enzymes to liver

G6P -> transporter -> ER

• > G6 phosphatase -> transporter -> cytoplasm
• > release from cell via diffusion

Disruption of any step leads to inability to defend BGL
(+) PKA -> expression

Question 6

Regulation of glycogen synthase

Answer 6

(-) phosphorylation
(Glucagon/epi -> AC -> cAMP -> PKA -> inactivates synthase)
(+) G6P
(+) insulin (inactivates PKA)

Question 7

Regulation of glycogen phosphorylase

Answer 7

(+) phosphorylation

(+) glucagon/epi
(-> PKA -> +(P) phosphorylase kinase -> +(P) phosphorylase)
(-) insulin (inactivates PKA)

(-) glucose - liver isoenzyme only
(+) AMP, Ca - muscle isoenzyme only
(Ca is through phos kinase)

Question 8

Gluconeogenesis overview

Answer 8

Kidney and liver only

Precursors:
 - lactate -> pyruvate (peripheral glycolysis, Cori cycle )
 - amino acids (muslce, alanine cycle)
 - glycerol (triglyceride)
NOT acetyl-CoA

Regulation:

• allostery, phosphorylation (PFK2 -> PFK1)
• expression (Pyruvate carboxylase, PEPCK, G6phos)

Question 9

Gluconeo from pyruvate

Answer 9

Pyruvate kinase is irreversible!
Need “end-around” to produce PEP from lactate or alanine
Regulation via expression
(+) glucagon via PKA

Pyruvate carboxylase
 Pyruvate + ATP -> oxaloacetate + ADP
 - requires biotin
 - in mitochondria
Oxaloacetate shuttle -> cytoplasm
 - malate dehydrogenase -> malate -> reverse
PEP-carboxykinase
 Oxaloacetate + GTP -> PEP + GDP

Question 10

Cori cycle

Answer 10

Muscle:
Glucose -> ATP + lactate ->
Liver:
Lactate + ATP + GTP -> glucose