11. Post Absorption Processing of Lipids Flashcards
What are lipids transported in in circulation?
Lipoprotein particles: chylomicrons
What is fat principally absorbed as?
2-monoacylglycerol
FAs
What are FAs converted to?
Acyl-CoA
Where are FAs converted to Acyl-CoA?
ER of intestinal mucosal cells
What converts FAs to acyl-CoA?
Acyl-CoA Synthetase
What happens once proteins and lipids are secreted from the smooth ER and golgi?
Released into extracellular space as fat droplets
Collected by local lymph
Transported via the thoracic duct to the left brachycephalic vein
What is the structure of monoacylglycerol?
Glycerol linked to a FA via an ester bond
What is the structure of triacylglycerol?
Ester derived from glycerol and 3 FAs
What is the structure of cholesterol ester?
Ester bond formed between the carboxylate group of a fatty acid and the hydroxyl group of cholesterol
What does utilisation of TAGs require?
Lipoprotein Lipase
Where is lipoprotein lipase not found?
Liver
Brain
What is LPL attached to?
Heparan sulphate glycoproteins on the surface of the capillary endothelium on adipose
What increases the activity of LPL?
Insulin
What happens to TAGs when going from a fed state to a fasting one?
TAGs are re-routed from adipose to muscle
Where do most of the FAs used in TAG synthesis in adipose tissue come from?
Chylomicrons
Where do most of the FAs used in TAG synthesis after a high carb meal come from?
Acetyl CoA
What form do FAs participate in TAG synthesis as?
CoA-thioesters
What form does glycerol participate in TAG synthesis as?
Glycerol-3-phosphate
How does insulin regulate fat synthesis?
Increases rate of glycolysis
Increases LPL activity
Induces glycerolphosphate-acyl transferase which catalyses the first step in TAG synthesis
What enzyme carries out the first cleavage of a FA from TAGs?
Hormone-sensitive adipose tissue lipase
What activates adipose tissue lipase?
Phosphorylation by cAMP-dependent Protein Kinase A
What are the most important human lipolytic agents?
Noradrenaline and adrenaline
How does noradrenaline work to promote TAG breakdown?
Acts via beta-adrenergic receptors, cAMP, Protein Kinase A
What are other lipolytic hormones?
Glucocorticoids
GH
Thyroid hormone
What conditions increase TAG hydrolisation?
Cold exposure
Stress
Physical exercise
What do free FAs bind to in circulation?
Albumin
Where does beta oxidation occur?
In the mitochondrion
What types of cells can’t oxidise FAs?
Neurons
Erythrocytes
How do short FAs enter the mitochondrion?
Passive diffusion
How do longer FAs enter the mitochondrion?
Converted to CoA-thioesters by Fatty Acyl CoA Synthetase
Carnitine transports acyl group across the membrane
Known as the carnitine shuttle
What is the carnitine shuttle composed of?
Carnitine Palmitoyltransferase 1 and 2
Carnitine-acylcarnitine translocase
What inhibits CPT-1?
Malonyl-CoA
What is the net result of beta oxidation?
Each cycle removes 2 carbons from the FA as acetyl-CoA
Production of NADH, H+ and FADH2
How does beta oxidation produce energy?
FADH2 and NADH feed into oxidative phosphorylation
Acetyl-CoA enteres TCA cycle
How is beta oxidation regulated?
Supply of free FAs
Activity of hormone-sensitive adipose tissue lipase
Inhibted by malonyl-CoA
Name 3 ketone bodies
Acetoacetate
B-hydroxybutyrate
Acetone
How are acetoacetate and B-hydroxybutyrate formed?
From Acetyl-CoA in the liver mitochondria by ketogenesis
How is acetone formed?
Spontaneous decarboxylation of acetoacetate
Where are ketone bodies especially important for energy?
Heart
Adrenal glands
Renal cortex
When are circulating ketone body levels high?
Fasting
Diabetes mellitus
Whenever fat breakdown exceeds carbohydrate breakdown
What is brown adipose tissue characterised by?
Good blood supply
High mitochondria and cytochromes
Low activity of ATP synthetase
What are the main clinical signs of Medium Chain Acyl-CoA Dehydrogenase Deficiency?
Intolerance to prolonged fasting Hypoglycaemia Impaired ketogenesis Hypoglycaemic coma Medium-chain dicarboxylic aciduria
