Lipids Flashcards
What are lipids?
- Heterogeneous organic molecules
- Insoluble in water (hydrophobic) but soluble in organic solvents
- Exist in cell membranes, as lipid droplets in adipose tissue, in blood lipoproteins
Biological functions of lipids
- Stored form of energy
- Structural element of membranes
- Enzyme cofactors
- Hormones
- Vitamins A,D,E,K
- Signalling molecules
Digestion and absorption of lipids
- Triacylglycerol main dietary lipid
- Others: phospholipids, cholesterol, cholesterol ester, free fatty acids
- Small intestine main site of digestion
Lipid digestion by pancreatic enzymes (lipases) is promoted by emulsification (dispersion) by bile salts and peristalsis (mixing)
Fatty acid nomenclature
18:0
contains 18 carbons and no double bonds
Essential fatty acids are
Linoleic and a-linolenic; must get these from plants
“bad fats (cardiovascular)” are
high in saturated fatty acids: e.g. stearic (beef).
(Saturated -huge role in myelination of nerve fibres and hormone production important in maintaining health).
“really bad fats”:
trans fatty acids, result from hydrogenation of vegetable oils e.g. hard margarine (man-made)
What are Essential fatty acids?
- Linoleic and linolenic acids are essential FA in humans
- Humans cannot introduce double bonds beyond carbon 9
- Must ingest essential FA
Arachidonic acid, a precursor of eicosanoids can be synthesized from linoleic acid
Omega (w)-3 fatty acids are derived from
linolenic acid as essential FAs.
E.g., eicosapentaenoic and docosahexaenoic acid
- Omega-3 FA lowers plasma cholesterol prevents atherosclerosis, lowers TAG prevents obesity, reduces inflammation.
- Omega-6 FA derived from linoleic are essential but not same benefits (???)
essential fatty acid deficiency symptoms
- Growth retardation
- Reproductive failure
- Skin lesions
- Kidney and liver disorders
- Subtle neurological and visual problems
essential fatty acid (omega 3) deficiency can lead to
depression
- inadequate intake alters brain activity or depression
alters fatty acid metabolism?
Attention deficit hyperactivity disorder
- lower levels of omega 3 cause more behavioural
problems
Triacylglyerols (TAG)(Triglycerides) are
Esters of fatty acids and glycerol
- Esters are neutral uncharged lipids
- Water insoluble TAG coalesce (come together) into lipid droplets in adipose tissue (major lipid component of adipose tissue)
- Dietary fuel and insulation
Phospholipids are composed of
glycerol bonded to two fatty acids and a phosphate group.
- Amphipathic - charged phosphate group as ‘head’ of a phospholipid is hydrophilic (attracted to water) whereas the hydrophobic ‘tails’ repel water.
main site of lipid digestion is
small intestine
main dietary lipid is
triacylglycerol
lipid digestion by pancreatic enzymes (lipases) is promoted by
emulsification (dispersion) by bile salts and peristalsis (mixing)
bile salts act as
- biological detergents to form emulsions and mixed micelles
- Saves lipids coalescing (coming together) in an aqueous environment
- Derivatives of cholesterol
bile salt are made up of cholic acid and
- taurine which made taurocholic acid
- glycine which made glycocholic acid
both are major bile salts
How do we digest triacylglycerols?
Most TAG degraded in small intestine by pancreatic lipase to monoacylglycerol + two FA
Digestion of cholesterol esters (and phospholipids)
- Cholesterol esters digested to cholesterol and free FA
- Phospholipids hydrolysed to FA and lysophospholipid
fat gets converted into
emulsified fats (through bile) and then fatty acids and glycerol (through lipase)
Uptake of digested lipids:
- Products of lipid digestion form
mixed micelles with bile salts.
Mixed micelles approach brush border membranes of enterocytes and release lipid products which enter cells by diffusion.
Short and medium chain FA do not require micelles for absorption
What is Steatorrhea?
Lipid malabsorption due to defects in bile secretion, pancreatic function or intestinal cell uptake results in steatorrhea
- Steatorrhea is excess fat in faeces. Stools float due to excess lipid, have an oily appearance and are foul smelling
- Gallbladder secretes bile. Removal of the gallbladder inhibits digestion and absorption of fats
Cystic fibrosis patients are prone to
steatorrhea as with their thickened pancreatic secretions, pancreatic enzymes are less able to reach the small intestine which is the primary site of lipid digestion
Utilisation of dietary lipids
What happens to absorbed fatty acids?
Intestinal cells resynthesize TAG, PL, CE for export
- insoluble so packaged with apoB-48 (solubilising protein) into chylomicrons for export
Chylomicrons are released by exocytosis into lymph then blood
What happens when blood chylomicrons reach tissue?
TAG in chylomicrons is hydrolysed to FA and glycerol by lipoprotein lipase
Lipoprotein lipase is found primarily in capillaries of skeletal muscle and adipose tissue
Resulting free FA used for energy or re-esterified to TAG for storage
Chylomicrons depleted of TAG are called chylomicron remnants – go to liver
Glycerol is used by liver to produce glycerol-3-phosphate (glycolysis & gluconeogenesis)
step 1 :
bile salts emulsify dietary fats in the
small intestine forming mixed micelles.
step 2:
intestinal lipases
degrade triacylglycerols
step 3:
fatty acids d other breakdown taken products are taken up by the
intestinal mucosa and converted into triacylglycerols
step 4:
triacylglycerols are incorperated with
cholesterol and apolipoproteins into chylomicrons.
step 5:
chylomicrons move through
the lymphatic sytstem and bloodstream to tissues
step 6:
lipoprotein lipase is activated by
apoC-II in the capillary.
converts triacylglycerol into fatty acids and glycerol
step 7:
fatty acids enter
cells
step 8:
fatty acids are
oxidised as fuel or reesterified for storage
Synthesis and storage of TAG
- In adipose cells TAG are stored as droplets that constitute the “depot fat”
- TAG is the most efficient storage form of fuel (highly reduced, nearly anhydrous (containing no water))
fatty acids are released by
lipoprotein lipase.
fatty acids are released when energy supply is low.
How are FA released from stored TAGin adipose tissue?
- FA released from stored TAG by hormone sensitive lipase (HSL)
- HSL activated by phosphorylation in response to epinephrine (aka adrenaline)
- High plasma glucose and insulin promote dephosphorylation (inactivation) of lipase
How are FA transported in blood?
- Free FA transported through blood in complex with serum albumin
- Albumin most abundant plasma protein with 2-7 binding sites for FA
- Most FA esterified (>90%)
- These carried in lipoproteins
Lipoproteins
TAGs, and cholesterol esters are insoluble in water and cannot be transported in blood or lymph as free molecules
lipoproteins are made up of
cholesteryl ester
phospholipid
unesterified cholesterol
apolipoprotein B-100
Lipoproteins
Hydrophobic cores :
TGs
cholesteryl esters cores
Lipoproteins
Hydrophilic surfaces :
unesterified cholesterol
phospholipids
apolipoproteins e.g.B100
Lipoprotein classes
Chylomicrons
VLDL
LDL
HDL
Lipoprotein classes
Chylomicrons
VLDL
LDL
HDL
Lipoprotein
Classified according to density (least to most)
- Chylomicrons –TAG rich (TAG from intestine to tissues). - VLDL –TAG rich (TAG from liver to tissue) - LDL – cholesterol rich (cholesterol to extrahepatic tissue – BAD cholesterol) - HDL – protein/cholesterol rich. (Transports cholesterol from tissue to liver for elimination– GOOD cholesterol)
LDL provides cholesterol to
peripheral tissues.
Too much LDL results in too little uptake and the protein on LDL becomes modified.
When this happens macrophages in arteries form foam cells and atherosclerotic plaques.
HDL sucks cholesterol out of the plaque and also provides cholesterol to the liver for bile synthesis and hormone synthesis.