3. Lipids & Ketone bodies Flashcards
Are lipids more or less reduced than carbohydrates?
More reduced - produce more energy
What are the 3 classes of lipids?
- FA derivatives - FA, TAG, phospholipids
- HMG derivatives - cholesterol, cholesterol esters, ketone bodies
- Vitamines - A,D,E, K
How are TAGs stored?
Anhydrous form as lipid droplets in adipose tissue
What triggers FA release from adipose tissue?
Low plasma [glucose] means that less glycerol-1-phosphate is produced in adipose cells, causing FA to be released into the circulation.
What are the 3 steps in FA metabolism in target tissues?
- Activation in cytoplasm
- Carnitine shuttle transport into IMM
- Beta-oxidation - C2 removed
What enzyme is responsible for FA oxidation?
Fatty acyl CoA synthase
What controls the rate of FA oxidation?
Carnitine shuttle, inhibited by Malonyl CoA
In beta oxidation, what are the intermediates linked to?
CoA - leave as Acetyl CoA
What is the fate of Acetyl CoA from beta oxidation?
TCA cycle to provide energy
Which tissues can beta oxidation occur in?
Most tissues with mitochronidria - Not brain, RBC or WBC
Can beta oxidation occur without O2?
No - needs NAD+ and FAD
What is the fate of glycerol released from adipose tissue?
transported back to liver, into glycerol phosphate which can enter glycolysis as DHAP or TAG synthesis.
Which enzyme converts glycerol to glycerol-1P?
Glycerol kinase
What 3 ketone bodies are produced in the body?
- Acetone
- Acetoacetate
- beta-hydroxybutyrate
Where are ketone bodies produced?
Acetone and b-hydroxybutyrate in mitochondia in the liver.
Acetoacetate is formed from decarboxylation of acetone.
Do ketone bodies need protein transport in the blood?
No, they are water soluble.
What condition may present with ketoacidosis?
Unmanaged type 1 diabetes
How does the liver know when to make ketone bodies from Acetyl CoA and not cholesterol?
When [glucose] is low, FA will be oxidised which produces NADH.
NADH inhibits the rate limiting enzymes of the TCA cycle.
What enzyme catalyses the conversion of HMG-CoA to acetoacetate?
Lyase
How does the insulin:glucagon ratio control ketone body synthesis?
Insulin = fed state. Inhibits Lyase and stimulates HMG CoA reductase. Glucagon = starvation. Stimulates lyase and inhibits HMG CoA reductase.
After two additional reactions, the glycerol released upon the hydrolysis of triacylglycerol can enter which pathway?
Glycolysis.
After phosphorylation to glycerol phosphate and conversion to dihydroxyacetone phosphate, glycerol can enter glycolysis. It can also a precursor for gluconeogenesis by these same reactions.
Why are ketone bodies a useful fuel source?
They can be used by all tissues containing mitochondria including the central nervous system
Which 2 pathways can tissues obtain cholesterol if they need it?
- Direct synthesis of cholesterol from acetyl CoA within tissues
- Receptor mediated endocytosis of LDL particles.
What happens in paracetamol overdose?
Normal metabolic pathway is saturated, alternative pathway producing NAPQI is used. NAPGI has a direct toxic effect on metabolites.
Glutathione conjugated to NAPQI, depleting liver of the important anti-oxidant.
