lipid metabolism Flashcards
dietary lipids
Triglycerides
Very energy dense
Cholesterol
Cannot be used for ATP synthesis
Required for cell and organelle membranes, steroid synthesis and bile salt production (lipid digestion)
Can be synthesised by liver
Phospholipids
lipid metabolism
Fatty acids are used to make ATP by many tissues in the fasting state
except glucose obligate tissues: brain, erythrocytes etc
Lipids used for ATP generation are transported as:
Triglycerides (in lipoproteins – chylomicrons and VLDL)
Fatty acids (bound to albumin) – called free fatty acids (FFA) or non-esterified fatty acids (NEFA)
Lipids are stored as triglycerides in tissues
Adipose tissue optimised for this
triglycerides
Triglycerides can be synthesised from carbohydrate and some amino acids
The principal regulators of lipid metabolism are insulin and (nor)adrenaline
lipid digestion
Lipid digestion occurs in small intestine
Pancreatic lipase and colipase – targets of Orlistat
break down TAG into 2 FAs and MAG (monoacylglyceride)
Enzymes also require bile salts
synthesized from cholesterol
secreted by liver through bile duct
emulsify fats to micelles (tiny fat droplets)
large lipid droplet —> bile salts (emulsifiers)—-> bile salts, pancreatic lipase, collapse—> water soluble micelles of FA,MAG
lipid absorption
- TAG re-formed in intestinal cell
- TAG packaged with cholesterol, apolipoproteins, other lipids to form chylomicrons
- Chylomicrons released into lymphatic system by exocytosis
lipoproteins
Transport triacylglycerols and cholesterol (as cholesteryl esters) in plasma
Transport of dietary lipids from intestine to liver (exogenous) by chylomicrons
Transport lipids from liver to peripheral tissues by VLDL, IDL and LDL or from peripheral tissues to liver by HDL (endogenous)
structure of human plasma lipoproteins
extracellular- single layer of phospholipids, apoproteins (apolipoproteins (multiple))
intracellular- cholesterol, cholesteryl ester, triacylglycerol
lipoproteins types- chylomicrons
– synthesised from dietary fatty acids and cholesterol. Transport as triglyceride and cholesterol esters. Transported to liver
lipoproteins- very low density lipoproteins
synthesised by liver from fatty acids and cholesterol. Transport as triglyceride and cholesterol esters.
As circulates, triglycerides removed by tissues. Lipoprotein gets smaller, more dense and cholesterol rich, becoming IDL (intermediate density lipoprotein) then LDL (low density lipoprotein)
lipoproteins types- high density lipoproteins
Synthesised by extrahepatic tissues
Takes excess cholesterol from peripheral tissues back to liver (where excreted as bile salts or repackaged into VLDL)
beta-oxidation
Generation of ATP from fatty acids
Fatty acids first added to CoA to form fatty acyl-CoA in cytoplasm
Uses ATP (similar to first stages of glycolysis using ATP)
Occurs within the mitochondrion
Fatty acyl-CoA must cross the inner mitochondrial membrane
requires carnitine carrier molecule
Carnitine derived from lysine and methionine (amino acids)
High levels of carnitine in muscle
beta-oxidation steps
Fatty acyl CoA are degraded by oxidation at the b-carbon
Occurs in rounds reducing size of fatty acyl chain by 2 carbons each time
Produces 1 FADH2, NADH and acetyl CoA (2 carbons) per turn
Ends up with a final acetyl CoA
ATP production in beta-oxidation
Acetyl CoA can be further oxidised to yield ATP (TCA cycle/oxidative phosphorylation)
e.g. the ATP yield of palmitate (C16) is106 ATP
Fatty acids are an excellent source of ATP
fatty acid synthesis
Fatty acids are built 2 carbons at a time
Limit is 16 carbons
Key regulatory enzymes are
Acetyl CoA carboxylase
Forms malonyl CoA
Fatty acid synthase
formation of malonyl CoA by acetyl CoA carboxylase
acetyle CoA ————-> malonyl CoA
(ATP—-> ADP + Pi, CO2, biotin)
fatty acid synthesis
acetyl CoA coupled to malonyl CoA
7 successive steps by multifunctional enzyme
fatty acid synthase
active in tissues that make fatty acids
Requires NADPH (Pentose Phosphate pathway)
Occurs in cytoplasm
fatty acid synthesis
Acetyl-CoA + 7 malonyl-CoA + 14 (NADPH + H+)
———>
(fatty acid synthase)
Palmitic acid (16C) + 7 CO2 + 14 NADP + 8 CoA + 6 H2O
fatty acid synthase
Intermediates in fatty acid synthesis are linked to an acyl carrier protein (ACP)
ACP has phosphopantetheine group attached to Ser of ACP
Phosphopantetheine also part of CoA
Pantothenic acid is vitamin B5
regulation of ACC and FAS- fed state
Insulin rapidly stimulates ACC
Fatty acid synthesis increased
Fatty acid oxidation decreased (as more malonyl-CoA)
Insulin stimulates glucose uptake into adipocytes (GLUT4)
Excess glucose after meal used for lipid synthesis
Insulin stimulates transcription of FAS gene
regulation of ACC and FAS- fasted state
Lack of insulin inhibits ACC
Fatty acid synthesis decreased
Fatty acid oxidation increased (as less malonyl-CoA)
Little glucose uptake by adipocytes as no insulin
