Post-absorption processing of fats. Flashcards
Cholesterol is a precursor for:
Bile salts, steroid hormones, vitamin D and membranes
Where are chylomicrons formed? Where are they released?
Intestinal epithelial cells. Released into lymph.
How do fatty acids arrive at peripheral tissues?
In chylomicrons/VLDL (released by lipoprotein lipase). From adipose tissue (broken down by hormone-sensitive lipase, transported bound to albumin).
What is the first step of fatty acid oxidation?
Activation to fatty acyl CoA in cytosol.
Where does the oxidation of fatty acids take place?
Mitochondria
What is required for the transport of long-chain fatty acids?
Carnitine and carnitine carrier protein - transports them across mitochondrial inner membrane.
What is produced from the oxidation of fatty acids?
Acetyl CoA - Krebs cycle
NADH and FADH - oxidised by electron transport chain
How many molecules of ATP are produced from the oxidation of one fatty acid?
108
What controls fatty acid metabolism?
Regulated by access of fatty acids to the mitochondria - controlled by conc. of malonyl CoA (produced by 1st step of fatty acid synthesis). Inhibits breakdown when energy is plentiful.
What are ketone bodies formed from?
Excess acetyl CoA
Where does the synthesis of ketone bodies occur?
Mitochondria of liver cells when body is fasting or during diabetes.
What is the most important step in cholesterol biosynthesis?
1st - acetyl CoA to mevalonate
How is cholesterol synthesis controlled?
Adjusting the activity or amount of HMG CoA reductase - controlled by cholesterol levels and energy levels.
What is the effect of insulin of HMG-CoA reductase
Stimulation (via dephosphorylation)
What effect do saturated fats have on lipoprotein levels?
Increase LDL
What effect do trans fats have on lipoprotein levels.
Can raise LDL and lower HDL
What is the aetiology of familial hypercholesterolaemia?
Lack of LDL receptors.
How does cholesterol contribute to the negative feedback loop that contributes to a reduction in the txn of HMG-CoA reductase (hence reduction in cholesterol synthesis).
Inhibits txn-enhancing signal.
Why is HDL considered ‘good cholesterol’?
Involved in reverse cholesterol transport - returning cholesterol from peripheral cells to the liver.
What is the initiating factor in atherosclerosis?
Damage to endothelial cells allows LDL to access subintimal space.
What happens to subintimal LDL to contribute to atherosclerosis?
Becomes oxidised and is internalised by macrophages. Accumulation of foam cells create bulge in vessel wall - atherosclerotic plaque. Fibrous collagen cap forms.
Why might an atherosclerotic plaque rupture?
There is a continued inflammatory response - induces macrophages to produce proteinase enzymes which degrade the fibrous cap.
What is the cause of alcoholic steatohepatitis?
Metabolism of large amounts of alcohol inhibits fatty acid oxidation and activated excess triglyceride synthesis (caused by high NADH).
What is the cause of non-alcoholic steatohepatitis?
Insulin resistance leads to increased insulin secretion - stimulates fatty acid synthesis.