Integration of metabolic regulation and organ specialisation

Question 1

Brain must have continual supply of glucose

Answer 1

2% of body mass; 20% of resting O2 consumptn
Massive amt of ATP needed for nerve impulse membrane potential
Brain stores v little glycogen
Glucose can be supplemented by ketone bodies
Depletion of oaloacetate for glucose synthesis in liver via pyruvate leads to generation of ketone bodies

Question 2

Skeletal muscle uses glucose (from glycogen, FA and ketone bodies)

Answer 2

30% resting O2 consumptn
Stored glycogen can be mobilised more rapidly than fat
Glucose can be metabolised anaerobically
Different ATP needs utilise different fuel resources

Question 3

Skeletal muscle contraction

Answer 3

Driven by ATP hydrolysis
Must respond to dramatic changes in workload
Short term ATP stores from phosphocreatine (4s supply)
Then switch to glycolysis
Then muscle fatigue
Longer term excretion uses oxidative phosphorylation

Question 4

Rapid high exertion in skeletal muscle req anaerobic metabolism

Answer 4

Anaerobic glycolysis happens because TCA is too slow for needed flux of ATP
Anaerobic decomposition of pyruvate generates lactate
Maximum exertion limited to ~20s
why?
-impt to prevent cell death from depletion of ATP
-mechanism for fatigue not known

Question 5

Cardiac muscle metabolism is mostly aerobic

Answer 5

in continuous use, so muscle fatigue is not an option

• very rich in mitochondria
• prefers FA for fuel
• can utilise all fuel options

Question 6

Adipose stores and releases FA and hormones

Answer 6

-Adipose is all over body
Most abundantly- under skin, in muscle, abdomen
Where adipose is deposited is hormonally controlled

Question 7

Glycerol-3-Phosphate levels help regulate lipogenesis or lipolysis

Answer 7

TAG storage req glycerol-3-P, derived from glycolysis

Therefore FA mobilisation depends on rate of glucose uptake

Question 8

Liver: metabolic clearing house of the body

Answer 8

• Maintains proper circulating fuel levels
• uniquely positioned for both exogenous and stored fuels
• ->FA and cholesterol are delivered as TAG in chylomicrons
• ->all others are released into portal vein, which drains directly to liver
• Liver buffers blood glucose
• ->Glucose to Glucose-6-P is carried out by Glucokinase (hexokinase isozyme active in liver)

Question 9

Product of glucokinase has several alternative fates

Answer 9

1. Low blood [glucose]: converted to glucose by glucagon signalling that initiates glycogen breakdown
2. Converted to glycogen
3. Converted to acetyl-CoA for other purposes (eg. FA synthesis)
4. Produce NADPH

Question 10

Fructose metabolism happens almost entirely in liver

Answer 10

Metabolism of fructose in liver req fructokinase (ordinary hexokinase not available)
-Fructose–> Fructose-1-phosphate
Fructose consumption has dramatically increased in decades (Sweetened drinks, high fructose corn syrup)
Metabolism of F1P produces glycerol-3-P and DHAP, which can be used to synthesise backbone of TAGs and glycerophospholipids

Question 11

Liver and TAGs (high fuel demand vs low fuel demand)

Answer 11

High fuel demand

• Liver degrades FAs by beta oxidation to acetyl-CoA
• Liver itself uses acetyl-CoA by TCA and oxidative phosphorylation
• Liver uses some oxaloacetate to generate pyruvate and subsequent gluconeogenesis
• Liver generates ketone bodies with excess acetyl-CoA

Low fuel demand

• FAs incorporated into TAGs
• VLDLs secreted into bloodstream for adipose tissue uptake

*Beta oxidation and FA biosyn occur in liver, but not same time