Lipid Respiration Flashcards
Where are fats derived from?
- Diet
- De novo biosynthesis in liver (gluconeogenesis)
- Storage depots in adipose tissue
How do bile salts solubilize fatty acids? What happens if they don’t?
Bile salts are generated in the liver and stored in the gall bladder. During digestion they pass from the bile duct into the small intestine. They emulsify fats in the intestine, aiding the digestion and absorption of fats and of fat soluble vitamins A, D, E and K. Lack of bile salts results in the majority of fats passing through the gut undigested and unabsorbed resulting in fatty stool (steatorrhea).
What is orlistat also called and what does it do?
A potent inhibitors of gastric and pancreatic lipases. Chemically synthesised derivative of lipstatin, a product of streptomyces toxytrini. Orlistat reduces fat absorption by 30% which is almost completely excreted by the faecal route. Effective in treating obesity for up to two years (according to large multi-centre randomized clinical trials). Main side effects:
Abdominal pain, Increased flatus, Steatorrhea, Urgency to defecate.
What are the 5 types of lipoproteins along with source and role?
- Chylomicrons produced in intestines and involved in dietary fat transport
- Very low density lipoproteins produced in liver and involved in endogenous fat transport.
- Intermediate density lipoproteins produced from VLDL and a precursor of LDL
- Low density lipoproteins produced from IDL and involved in cholesterol transport.
- High density lipoproteins are produced in the liver and involved in reverse cholesterol trasnport.
How are chylomicrons formed?
Digested dietary products are absorbed by enterocytes that line the brush border of the small intestine. Triglycerides are resynthesised under control of several enzymes prior to incorporation into chylomicrons. This is transpoted via lymphatics into bloodstream where it picks up apoproteins from HDL.
How are chylomicrons broken down?
Chylomicrons travel from the lacteals of the small intestine to thoracic duct and left subclavian vein where it enters the bloodstream. The apoproteins on its surface then attach to lipoprotein lipases lining the capillary endothelium, which hydrolyse the phospholipids making up the chylomicron membrane. These lipases are found lining a variety of tissue including adipose, skeletal muscle and heart. The fatty acids then undergo beta oxidation while the glycerol is taken away to the liver to take part in gluconeogenesis.
Describe the anatomy of a lipoprotein
Lipoproteins solve problem of transporting hydrophobic molecules in an aqueaus environment. Are composed of pospholipid monolayer containing cholesterols and apoproteins, surrounding a core of cholesterol esters and triacylglycerols.
How are cholesterol esters synthesised?
Synthesised in plasma from cholesterol and acyl chain of phosphatidylcholine (lecithin) via a reaction catalysed by LCAT (lecithin-cholesterol acyltransferase)
Contrast HDLs and LDLs
HDLs are considered good cholesterol as their function is to take cholesterol from peripheral tissues back to the liver for use or disposal and hence lower the total serum cholesterol levels. LDLs considered bad as prolonged high levels result in atherosclerosis. LDLs transport cholesterol made in liver to peripheral tissues and almost 40% of their weight is made up of cholesterol esters.
Describe beta oxidation of fatty acids until acyl CoA within matrix
Fatty acids are converted to acyl CoA via action of acyl CoA synthetase and ATP converted to AMP as two bonds’ energy used. Generation of acyl CoA molecule happens on outside of the mitochondrial membrane and hence it is transferred inside by action of a carnitine shuttle through a translocase. The acyl group from an acyl CoA outside the membrane is transferred to a carnitine to form acyl carnitine by action of acyl transferrase 1. This then moves across the tranlocase and the reverse reaction happens in the matrix catalysed by acyl transferrase 2. This reforms acyl CoA.
Describe beta oxidation in matrix
Once in the matrix, the acyl CoA undergoes series of oxidation, reduction, oxidation, thiolysis reactions altogether called beta oxidation. Results in production of one acetyl CoA molecule and an acyl CoA species 2 carbons shorter than original. Each beta oxidation cycle consecutively removes 2 carbons and hence 16 molecule palmitoyl CoA produces 8 acetyl CoA in 7 beta oxidation reactions. Total output: 8 Acetyl CoA, 7 NADH, 7 FADH2.
What are ketone bodies and when are they formed?
Acetyl CoA generated from beta oxidation only enters TCA cycle when glucose and fat metabolism are balanced as it requires oxaloacetate for entry which is formed from pyruvate. When fat breakdown predominates, acetyl CoA forms acetoacetate, D-3-hydroxybutyrate and acetone collectively known as ketone bodies.
Describe fatty acid biosynthesis
Fatty acids are formed sequentially by decarboxylative condensation reactions involving molecules acetyl CoA and malonyl CoA and following each round of elongation, fatty acid undergoes reduction and dehydration in sequential order by action of ketoreductase, dehydratase and enol reductase. Growing fatty acyl group linked to an acyl carrier protein. Only 2 enzymes involved in synthesis known as: Acetyl CoA carboxylase and Fatty Acid Synthase.
What are the distinctions between fatty acid synthesis and degradation?
Carriers: Synthesis uses ACP while degradation uses CoA
Reducing power: Synthesis NADPH and degradation FAD/NAD+
Locations: Synthesis in cytoplasm and degradation in matrix
What is the overall lipogenesis reaction?
Acetyl CoA + 7 Malonyl CoA + 14 NADPH + 14 H+
——> Palmitate (C16) + 7 CO2 + 6H20 + 8 CoA-SH + 14 NADP+
