integration of fuel metabolism

Question 1

Allosteric effects of Metabolism

Answer 1

Short term, minutes

PFK-1 in glycolysis
Fructose 1,6 bisphosphatase 1 in gluconeogenisis
acetyl CoA carboxylase in FA synthesis
PDH and P carboxylase in pyruvate metabolism

Effectors are typically small molecules:
Citrate (-) PFK1
Citrate (+) acetyl CoA carboxylase
malonyl CoA (-) CPT 1 (inhibits B oxidation)
Fructose 2 6 bisphosphate (+) PFK1
Fructose 2 6 bisphosphate (-) FBPase -1
Acetyl CoA (-) PDH
Acetyl CoA (+) Pyruvate carboxylase
NADH (-) PDH and TCA cycle
ATP and ADP levels

Question 2

Covalent modification

Answer 2

intermediate term regulation

Phosphorylation by protein kinases
cAMP-dependent protein Kinase (PKA)

AMPK inactivates acetyl CoA carboxylase

Question 3

Enzyme levels

Answer 3

for long term
PEPCK gene is regulated
insulin

Question 4

Compartmentalization

Answer 4

Strictly Cytosolic: Glycolysis, PPP, FA synthesis

Strictly Mito: TCA, Oxidative phosphorylation, B oxidation of FAs, Ketone body formation

Bothe: Gluconeogensis, Urea cycle

Question 5

Metabolic specialization of organs

Answer 5

Hormone sensitive lipase gene : only in adipocytes
Pyruvate kinase is regulated by phosphorylatio only in the liver
Cori cycle links skeletal muscle gluconeogenisis in the liver

Question 6

Fed state

Answer 6

liver: acts primarily as glucose utilizing organ following a meal
Adipocytes: droplets of TGs occupy majority of adipocyte
Skeletal muscle: glucose is the major energy source
Brain: Glucose is the major energy source following a meal

Question 7

Fasted state: early

Answer 7

Early fasting is the reverse of fed state

Liver: glycogen, then gluconeogenisis to maintain blood glucose levels in fasted state

Adipocytes (FA metabolism)
Skeletal muscle (FAs as energy source)
Brain: short term brain will use glucose (spared by other tissue), as time goes on ketones are greatly increased and are used as fuel by the brain

Question 8

Starvation

Answer 8

Liver: mainly gluconeogenisis and ketone body production
brain uses glucose and ketones

Adipocytes: FA mobilization

Skeletal muscle: FA as fuel

Brain : switch to use more ketones

Question 9

Utilization of muscle protein for gluconeogenisis

Answer 9

Alanine is broken away from muscle and deaminated in liver for pyruvate for the gluconeogenisis. But as time goes on less muscle breakdown because brain uses more ketones

Question 10

Is fat a carbon source for gluconeogenisis

Answer 10

no

Question 11

Metabolic dysregulation in diabetes

Answer 11

Diabetes results in a breakdown of the hormonal mechanism that normally balance the production and utilization of metabolic fuels

Type 1 diabetics have no insulin (defective/absent B cells)
Type 2 produce insulin but are resistant to its effects

Failure of some tissues (Muscle and fat) to take up glucose in an insulin dependent GLUT 4 manner, contributes to glucosuria, and a higher rate of gluconeogenisis

Type 1 Diabetes is managed by insulin (if altered metabolism in anyway–> diabetic ketoacidosis), adipocytes are more lipolytic and the liver is more B-oxidative, gluconeogenic, and ketogenic and resemble long term starvation

Type 2 diabetics rarely get keto acidosis, but actually develop hyper triglyceridemia