Ketogenesis Flashcards
What are the sources of energy in the body
Carbohydrates
Fats
Lipids
How long can glycogen stores sustain energy levels
12 hours
How long can lipid energy reserves provide energy
up to 12 weeks
When is protein stores used
Used when muscle glycogen stores fail
What do fatty acids contain
Carboxylic head with aliphatic group
Saturated or unsaturated
What are most fatty acids derived from
Triglycerides and phospholipids
Where does fatty acid oxidation occur
Cytoplasm
Describe Acyl-CoA
12 carbons
Can be diffuse into the mitochondrial membrane
What is the order of fatty acid activation
Fatty acid
Acyl adenylate
Acyl-CoA
What does fatty acid use and produce
Use - ATP, CoA-SH
Produce - PPi, AMP
What are the features of most dietary acids
> 14 carbons
Taken through mitochondrial membrane using carnitine shuttle
What happens to most acetyl-CoA under normal metabolic conditions
Utilised via the TCA acid cycle to produce glucose
What happens to a small amount of acetyl-CoA under normal metabolic conditions
Converted into ketones
What are ketones produced
By liver from acetyl-CoA
3 examples of ketones
Acetone
Acetoacetate
Beta-hydroxybutyrate
What happens during high rate of fatty acid oxidation
Large amounts of acetyl-CoA are generated
Why does ketogenesis occur
When large amounts of acetyl-CoA are produced
Exceeds capacity of the TCA cycle
In ketogenesis what can acetoacetate undergo
Spontaneous decarboxylation to acetone
OR
Enzymatically converted to beta-hydroxybutyrate
Where can acetoacetate:succinyl-CoA be found
All tissues but hepatic tissue
What are ketone bodies utilised by
Extrahepatic tissues through conversion of beta-hydroxybutyrate and acetoacetate to acetoacetyl-CoA
Required acetoacetate:succinyl-CoA
What is ketogenesis regulated by
- Release of free fatty acids from adipose tissue
- High concentration of glycerol-3-phospahte in the liver results in triglyceride production, whilst low level results in increased ketone body production
- Demand for ATP is high, acetyl-CoA is likely to be further oxidised via the TCA cycle to carbon dioxide
- Fat oxidation is dependant upon the amount of glucagon (activation) or insulin (inhibition) present
Describe ketoacidosis
Occurs in insulin-dependent diabetics when dose is inadequate or because of increased insulin requirement (infection, trauma, acute illness)
Often presenting feature in newly diagnosed type 1 diabetics
Occurs in chronic abuse
Patient presents with hyperventilation and vomiting
Diabetic ketoacidosis
What are the three things that can occur in insulin deficiency
Inhibition of glycolysis and stimulation of gluconeogenesis
Glycogen breakdown and inhibition of glycogen synthesis
Increased lipolysis (increased fatty acids)
What does Inhibition of glycolysis and stimulation of gluconeogenesis lead to
Hyperglycaemia
What does Glycogen breakdown and inhibition of glycogen synthesis lead to
Hyperglycaemia
What does increased lipolysis (increased free fatty acids) lead to
Increased acetoacetate and beta-hydroxybutyrate
What are the consequences of ketoacidosis
Excessive ketones lower pH in the blood - impairs the ability of haemoglobin to bind to oxygen
pH - low
pO2 - high
pCO2 - low
HCO3 - low
What are ketones
Relatively strong acids (pKa approx. 3.5)
