Fatty Acid Oxidation And Ketones Flashcards
What are the sources of energy in the body?
Carbohydrates
We have enough glycogen to sustain energy levels for 12 hours.
Fats
Lipid energy reserves provide energy for up to 12 weeks
Protein
Used when muscle glycogen stores fail.
What are fatty acids?
Carboxylic head group with aliphatic tail.
•Saturated and unsaturated
Most are derived from triglycerides and phospholipids
Hydrophilic head
Hydrophobic tail
Where are fatty acids activated?
Cytoplasm
Where are fatty acids oxidised?
Mitochondria
How do < 12 carbons fatty move into the mitochondrial membrane?
Diffusion
How do > 14 carbons fatty move into the mitochondrial membrane?
Taken through mitochondrial membrane using the carnitine shuttle
How is acetyl-CoA utilised under normal metabolic conditions?
Most Acetyl-CoA is utilised via the TCA acid cycle to produce glucose.
A small proportion of Acetyl-CoA is converted into ketones.
What are ketones?
Molecules produced by the liver from acetyl-CoA.
Have a characteristic fruity/nail polish remover-like smell
How is acetyl-CoA utilised during high rates of fatty acid oxidation?
Large amounts of acetyl-CoA are generated.
This exceeds the capacity of the TCA cycle which results in ketogenesis.
What happens in ketogenesis?
•Acetoacetate can undergo spontaneous decarboxylation to acetone, or be enzymatically converted to beta-hydroxybutyrate.
•Ketone bodies utilised by extrahepatic tissues through conversion of beta-hydroxybutyrate and acetoacetate to acetoacetyl-CoA.
•This requires the enzyme acetoacetate:succinyl-CoA transferase, which is found in all tissues but hepatic tissue.
What is ketogenesis affected by?
Release of free fatty acids from adipose tissue.
A high concentration of glycerol-3-phosphate in the liver results in triglyceride production, whilst a low level results in increased ketone body production.
When demand for ATP is high, acetyl-CoA is likely to be further oxidised via the TCA cycle to carbon dioxide.
Fat oxidation is dependent upon the amount of glucagon (activation) or insulin (inhibition) present.
What is the clinical significance of ketogenesis?
•During normal physiological conditions the production of ketones occurs at a low rate.
•Carbohydrate shortages cause the liver to increase ketone body production from acetyl-CoA.
•The heart and skeletal muscles preferentially utilise ketone bodies for energy preserving glucose for the brain.
What is ketoacidosis?
•Occurs in insulin-dependent diabetics when dose is inadequate or because of increased insulin requirement (infection, trauma, acute illness).
•Is often the presenting feature in newly diagnosed type 1 diabetics.
•Also occurs in chronic alcohol abuse.
•Patients present with hyperventilation and vomiting.
What can diabetic ketoacidosis lead to?
Insulin deficiency:
- Inhibition of glycolysis and stimulation of gluconeogenesis -> Hyperglycaemia
- Glycogen breakdown and inhibition of glycogen synthesis -> Hyperglycaemia
- Increased lipolysis (increased free fatty acids)
-> Increased acetoacetate and beta-hydroxybutyrate
What can alcoholic ketoacidosis lead to?
High Blood EtOH Concentration
Depleted protein and carbohydrate stores:
- Increased lipolysis (increased free fatty acids) -> Increased ketone production
- Impaired gluconeogenesis -> Increased lipolysis (increased free fatty acids) -> Increased ketone production
- Decreased insulin and increased glucagon production -> Increased lipolysis (increased free fatty acids) -> Increased ketone production
