Metabolic Disorders Flashcards
What metabolic pathways oppose each other?
Glycolysis and gluconeogenesis
Beta oxidation and fatty acid synthesis
What must happen before triacyl glycerols can be used for metabolism?
They must by hydrolysed by lipases to release FA and glycerol
What are the 3 phases of fatty acid catabolism?
1) Activation of fatty acids (occurs in the cytosol)
2) Transport activated FA into mitochondria
3) Beta oxidation
What is the product of fatty acid catabolism?
Acetyl CoA
What happens during beta oxidation?
Successive removal of 2C units
Where does beta oxidation take place?
In the mitochondria
Where does stage 1 of fatty acid catabolism take place?
ER or cytosolic side of outer mitochondrial membrane
What happens in stage 1 of FA catabolism?
Fatty acid + HS-CoA + ATP -> Fatty acyl-CoA + H2O + AMP + PPi
What happens during phase 2 of fatty acid catabolism?
FA is transported to matrix of the mitochondria via carnitine
What happens to fatty acyl-CoA in stage 3 of fatty acid catabolism?
Beta oxidation. In this process acetyl CoA is formed which takes 2 carbons per cycle from the fatty acid.
A FADH2 and an NADH are gained every cycle.
14 carbon fatty acid would form 7 acetyl CoAs.
What happens if carnitine transport is defective?
Variability associated with hepatomegaly, liver disease, hypertrophic cardiomyopathy and potential arrhythmia.
Mild recurrent muscle cramping - severe weakness - death
What are the 2 different kinds of carnitine metabolism disorders?
Primary: Low carnitine in muscle, kidney and heart (not liver) overcome by dietary carnitine therapy
Secondary: Genetic defect in beta oxidation resulting in increased level of acylcarnitines.
What happens to metabolism in primary carnitine metabolism disorders?
Long chain FA oxidation is compromised and this effect is overcome by dietary carnitine therapy
What happens in secondary carnitine metabolism disorders?
Carnitine is excreted in urine
in type I muscle weakness and myoglobinuria
In type II (in infants) it is precipitated by fasting causing hypoketotic, cardiac malfunction and death
How is secondary carnitine metabolic disorders treated?
By avoiding starvation and diet low in long chain fatty acids
What are ketone bodies?
Lipid based energy source that is water soluble and produced primarily by the liver. They are used by CNS in starvation as well as skeletal and cardiac muscle.
What do neonates use ketone bodies for?
Precursors for lipid synthesis
What kind of molecules are ketone bodies?
Ketone bodies are acidic (ketone bodies is a bad name)
What are the products of ketone synthesis?
2 Acetyl-CoA molecules are converted into beta-hydroxybutyrate and acetone (dead end product responsible for fruity breath)
What are the roles of fatty acids in the body?
Fuel storage
Signalling
Components of membrane lipids
What happens in the liver when excess alcohol is consumed?
Alcohol conversion to FA in alcoholic liver disease contributes to liver failure
Which fatty acids does the body need to get from external sources?
Highly unsaturated fatty acids with double bonds near the methyl end (omega 3s)
What is the main pathway for FA synthesis?
Acetyl CoA -> Palmitic acid (16:0, saturated)
Other fatty acids can be made from palmitic acid
Where does fatty acid synthesis occur?
Cytosol of liver and mammary glands