Which lipids are used as fuel
Triacylglycerols
Which lipids are used in membranes
Glycerophospholipids
Cholesterol
Which lipids are used in lipid digestion
Bile salts (from cholesterol)
Which lipids are used in communication
Steroid hormones (from cholesterol)
Which lipids are used in vision, growth
Vitamins
Triacylglycerols composed of
Glycerol and three fatty acids
Triacylglycerols joined by
Ester bonds
Triacylglycerols efficient form to
Store energy
Body has almost unlimited ability to store these
Can be saturated or unsaturated
Fatty acids
Have variable length
Sources of lipids
Diet
Carbohydrates (in liver)
Major dietary lipid
Triacylglycerols
Digestion of dietary lipids: what emulsifies
Bile salts
Digestion of dietary lipids: what breaks down fatty acids from triacylglycerols
Lipases
Digestion of dietary lipids: fatty acids form
Micelles, absorbed by epithelial cells, packaged as chylomicrons
Chylomicrons
Comprised of layer of phospholipids (hydrophilic head, hydrophobic tails)
Apoproteins added in RER, packaged together in golgi and then become part of chylomicron
What happens to chylomicrons?
Triacylglycerols digested by lipoprotein lipase (LPL)
LPL produced by adipose, muscle and lactating mammary gland cells
Regulated by insulin
Fatty acids absorbed by cells; other remnants absorbed by liver
HDL (high density lipoprotein)
Mature them into final chylomicrons by adding components
Lipoprotein lipase sat on surface of cells
Recognise apoproteins (e.g. C2) Receptor and enzymes Digesting fatty acids, remnants back into blood stream, apoproteins recognised by liver
Endogenous lipids
Fatty acids synthesised in liver Glucose is source of carbons Reactions occur in cytosol Fatty acids can be stored as triacylglycerols, oxidised as fuel or used to make components of membranes Packaged with proteins to form VLDL
Endogenous lipids
Fatty acids synthesised in liver
Glucose is source of carbons
Reactions occur in cytosol
Fatty acids can be stored as triacylglycerols, oxidised as fuel or used to make components of membranes
Packaged with proteins to form VLDL (released to blood)
Functions of TCA cycle except for to produce energy
To make fats
e.g. Citrate –> fatty acid synthase
VLDL
Newly formed triaglycerides packaged into lipoproteins for secretion
Very low density lipoprotein
In this form they are transported to other tissues
Similar structure to chylomicron
VLDL Fate
Triacylglycerols digested by lipoprotein lipase (LPL)
LPL produced by adipose, muscle and lactating mammary gland cells
Regulated by insulin
Fatty acids absorbed by cells
VLDL remnant remains
Fatty acid oxidation
Fatty acids are important fuel source
During fasting, fatty acids become main energy source
Long chain fatty acids released from adipose tissue, stimulated by < insulin and > glucagon
Taken up by other tissues e.g. muscle
Several different pathways but main one is beta-oxidation
Beta-oxidation
Fatty acids enter tissues by diffusion
Then activated to acetyl CoA, producing NADH and FAD2H
Repeated until all Cs have been converted to acetyl CiA (2C)
Acetyl CoA can enter TCA cycle
Fatty acids can be very long, containing many carbons, producing a lot of energy
Beta-oxidation
Fatty acids enter tissues by diffusion
Then activated to fatty acyl CoA using ATP
Fatty acyl-CoA transported into mitochondria
Then activated to acetyl CoA, producing NADH and FAD2H
Repeated until all Cs have been converted to acetyl CiA (2C)
Acetyl CoA can enter TCA cycle
Fatty acids can be very long, containing many carbons, producing a lot of energy
Fed vs fasting
Fed: triacylglycerols being taken up into tissues
Fasting: released to bloodstream
Cholesterol
Can be synthesised or obtained from diet Major component of blood lipoproteins Important as: -component of cell membranes -precursor of bile salts -precursor of steroid hormones -precursor of vitamin D
Cholesterol absorption
Enters gut enterocytes predominantly by diffusion
Cholesterol cannot be fully metabolised - entry must be regulated
Enterocytes transport excess back into gut lumen
-cholesterol and bile salts excreted in faeces
Defects in proteins which transport cholesterol out of leads to chlolesterol accumulation and cardiovascular disease
Cholesterol synthesis
Occurs in cytosol (mainly liver) 4 stages: 1. Acetyl-CoA --HMG-CoA reductase --> mevalonate 2. Mevalonate --> isoprenes 3. Isoprenes (5C) --> Squalene (30C) 4. Squalene ---> Cholesterol
Cholesterol fate
Secreted from liver as:
- bile salts
- ->stored in gallbladder
- ->secreted into gut
- ->aid digestion by emulsifying fat
- biliary cholesterol
- ->secreted into gut
- ->can be reabsorbed
- cholesterol ester
- ->packaged in VLDL and transported to tissues
Bile salts
Charged molecules, effective as detergents
Predominantly recycled to liver
Cholesterol transport
Cholesterol and cholesterol esters transported in lipoproteins
Cholesterol helps to stabilise lipoprotein
Cholesterol cell entry
When triglycerides removed from VLDL and absorbed, VLDL ‘remnant’ remains
Converted to IDL and then LDL
LDL contain a lot of cholesterol and cholesterol esters
This can be:
-returned to liver to make more VLDL
-taken up by other cells needing cholesterol
(membrane synthesis and steroid hormone synthesis)
Excess LDL can be endocytosed by macrophages
This can cause inflammation and contribute to atherosclerosis
What happens to excess LDL?
Excess cholesterol taken up by macrophage –> foam cell
Creates turbulence/ narrowing
Damages blood vessel
Thrombus develops whilst trying to heal BV
Major cause of cardiovascular disease
How is cholesterol taken up by cells
LDL particle containing apoprotein and cholesterol ester recognised by cell membrane –> receptor-mediated endocytosis
Useful stuff absorbed by endosome, digested by lysosome, used by cell
LDL receptor recycled out of cell and used again
Statins
Used to combat high cholesterol levels in the blood
Competitively inhibit HMG Co-reductase, an enzyme required for cholesterol synthesis
Structural analogues of natural substrate, compete for binding - have higher affinity
-mimic part of substrate that fits into active site of enzyme to inhibit it
What affects action of HMG-CoA reductase?
Cholesterol, glucagon and cholesterol lowering drugs inhibit it.
Insulin increases its action