BC 30

Question 1

Metabolic Priorities for Liver in Fasting State (5-24)

Answer 1

1. FA Oxication (TCA and ETC) for hepatocytes own energy needs

Service Acts
1)Ketogenesis-utilize surplus acetyl coA to generate ketone bodies for export

2) Glycogenolysis (BG homeostasis)
3) gluconeogenesis, utilize C skeletons from amino acids

Question 2

Protein sparing compounds and associated state

Answer 2

Fed state: dietary carbs

Short fast: Liver glycogen

Long fast: Ketone bodies

Question 3

What three glycolysis reactions are irreversible and must be circumvented

Answer 3

Pyruvate Kinase,
PFK 1
Glucokinase

Question 4

liver vs Renal Gluconeogenesis for bodies needs

Answer 4

Short term fasting

• liver 90%
• kidney 10%

long term fasting

• liver 50%
• kidney 50%

Question 5

gluconeogenesis steps

Answer 5

Pyruvate –>OAA by Pyruvate Carboxylase

Shuttle out of Mito
OAA–>Malate by NADH
-exits Mitochondrial membrane
Malate–>OAA by NAD+

OAA–>phosphoenol pyruvate (PEP Carboxykinase)
-several more reversible reactions to F16BP

F16BP–> F6P by FBPase1

• RATE LIMITING
• how do FBPase1 and FBPase relate?
• F6P to G6P reversible reaction

G6P–>Free Glucose by Glucose 6 Phosphatase
-ONLY IN LIVER and kidney cortex

Question 6

Cori Cycle

Answer 6

cyclic catabolism of glucose/lactate in RBC and Muscle and gluconeogenesis in liver

-significance: shift in metabolic burden of breakdown from those tissues to the liver

Gluconeogenesis will also only run if sufficient ATP and Precursors are present (glycogenic AA or lactate)

• lactate from RBC and exercise
• –both in anaerobic conditions

Question 7

Step One Gluconeogenesis

Answer 7

Pyruvate –> OAA by pyruvate carboxylase

Puts a CO2 on pyruvate to make OAA. Same reaction used for the TCA priming

• Allosterically regulated by mitochondrial AcCOA
• -Increased AcCoA activates PC (inh PDHC)
• -AcCoA increased in fasting due to FA ox

ATP consumption-activation and transfer of CO2 by biotin coenzyme during caboxylation of pyruvate.
-all carboxylases require biotin coenzyme, provides the binding of CO2

Question 8

OAA shuttle out side IMM

Answer 8

OAA unable to cross IMM
reduced to Malate by NADH

malate passes through

oxidized to OAA by NAD+

Question 9

Step 2 Gluconeogenesis

Answer 9

OAA–>PPPy by PEP Carboxykinase (HYDROLIZE GTP)
-carboxylates and phosphorylates OAA

-more reversible reactions to F16BP

Question 10

Step 3 Gluconeogenesis

Answer 10

F16BP–>F6P by Fructose Bisphosphatase
-RATE LIMITING STEP

can be allosterically regulated: FBPase inhibited by AMP and F26BP (allosteric activator of PFK1)

Hormonally regulated

• F26BP levels regulated by IG ratio via combo enzyme PFK2/FBP2
• increased IG increase cAMP increase PKA and phosphorylates PFK2 inactivating it. FBP2 active decreasing F26BP increasing gluconeogenesis
• reciprocal hormone regulation F26BP increased by PFK2

Question 11

Step 4 Gluconeogenesis

Answer 11

G6P enzyme shared with glycogenolysis

• ONLY IN LIVER
• G6P–>free glucose (dephosphorylation)

freed to blood