Flashcards in Digestion,Transport,Storage ofLipids_Molecules Deck (95):
What problems does digestion and transport of lipids bring about?
Insolubility of lipids in water
What property do enzymes that act on lipids have?
Soluble proteins or membrane proteins at the aqueous interface
How are lipids and products of their digestion transported?
Through aqueous compartments within the cell as well as in the blood and tissue spaces
What is the average daily consumption of lipids?
80g of fat
above or equal to 30% of caloric intake (recommended approx. 20%)
Triglycerides comprise approximately of how much of our dietary lipid consumption?
90% of our dietary lipid consumption
What is the remainder of our dietary lipid consumption made of?
Cholesterol and cholesterol esters, phospholipids and non esterified (free) fatty acids
Where does digestion occur?
Mainly in duodenum with absorption occurring in the small intestine
What is absorbed in the small intestine during digestion?
1) lipases (TGs)
2) Cholesterol esterases (cholesterol esters)
3) Phospholipases (phospholipid)
What is a major site of lipid metabolism?
What happens during lipid metabolism in the liver?
Integration of endogenous production with exogenous (i.e. dietary) supply
What is synthesised and distributed in the liver?
5) Cholesterol and derivatives (e.g. bile salts)
6) ketone bodies
How does the lipid metabolism get 80% of energy needs?
Through FA oxidation
What are both FA and TG synthesis in circumstances of?
What are TG in circumstance of?
Dietary FA abundance
What are the reaction products of enzymatic digestion of triacylglycerols?
3) free FA
What are bile acids?
Amphipathic lipids which act as biological detergents
Where is bile acids and bile salts synthesised and stored in?
In liver from cholesterol and stored in gall bladder
How is bile salts and bile acids secreted?
Secreted via bile duct into duodenum
What is the difference between bile salts and bile acids?
Bile salts more soluble and less cytotoxic than bile acids
What aids digestion?
Solubilise dietary lipids
What happens when you dollies dietary lipids?
90-95% reabsorbed in ileum, 5-10% excreted
What does bile salts and bile acids do
Emulsify dietary lipids and facilitates the action of pancreatic lipase
- Disperses large lipid droplets into smaller ones (emulsification)
- Pancreatic lipase requires a second protein (colipase) for activity
What does dispersing large lipid droplets into smaller ones do?
Increase SA for pancreatic ligases to work on
What does pancreatic lipase inhibitor do?
Reduce lipid absorption
What effects can be seen with pancreatic lipase inhibitor?
modest weight loss (5-10% weight loss over 1 year)
What are examples of pancreatic lipase inhibitors?
Orlistat or Xenical
What does the pancreatic lipase inhibitor do?
Increase lipid retention in gut can have unpleasant side effects
1) Steatorrhea (loose, oily stools) and flatulence
What is recommended for people with pancreatic lipase inhibitor?
1) Recommended that meal fat content should not exceed 15g to minimise side effects
2) Need to take vitamin supplement to prevent deficiency of fat soluble vitamins
What is the diameter of the mixed micelle?
4 - 8 nM in diameter
What forms the mixed micelles?
Reaction products (free FA, monoacylglycerol, diacylglycerol, cholesterol, phospholipids and other lipids) form mixed micelles with bile salts
What is process of the lipid absorption and processing in enterocytes?
1) Enter cell by facilitated diffusion (membrane transporters)
2) TAG, PL and CE are (re)synthesised in ER, packaged into chylomicrons and released into lymph cells
3) Glycerol, short chain FA may be released directly into circulation
1) Synthesis of Cholesterol esters
2) Synthesis of phospholipids
3) synthesis of TS
What is not absorbed during the process of lipid absorption and processing in enterocytes?
What can reduce cholesterol absorption in the gut?
Consumption of plant sterols and stanols
2-3 g per day can effectively lower LDL cholesterol by 10% (0.3-0.6mmol/l)
reduce CHD risk by 25%
What is Ezitimibe do?
Inhibits NPC1L1 protein (sterol transport protein) on the enterocyte brush border and heptabiliary interface
What is bile acid (sequesterants) resins do?
Inhibit bile acid absorption in enterohepatic circulation - promotes increased bile acid/salt production and thus a lowering of circulating cholesterol
What is the summary of TG breakdown and absorption in the GIT?
1) TG too hydrophobic to be digested and absorbed
2) Most be 'solubilised' by bile salts and broken down to MAG/DAG and FAs
3) MAG, DAG and FAs can be absorbed
4) TG are then 'resynthesises' in enterocytes, packaged into lipoprotein particles and transported to liver and other tissues
How do lipids transported in special complexes?
Lipids such as TGs and cholesterol are insoluble in plasma and therefore are transported in special complexes termed lipoproteins
What are lipoproteins consisted of?
of a core of hydrophobic lipids surrounded by a 'skin' of amphipathic lipids and proteins termed apolipoproteins
How do the special complexes termed lipoproteins differ?
Differ in size, lipid content, apolipoprotein content, density (ratio of lipid to protein) and function
Where do chylomicrons form?
In the intestines
Where do HDL and VLDL assemble in?
In the ER of liver cells
is LDL made directly?
No, it evolves from VLDL
How are free FAs (NEFAs) transported?
As complexes with serum albumin a low affinity non specific lipid binding protein
What are examples of the lipoproteins?
What is the general structure of a lipoprotein particle?
3) TG and CE made from cholesterol ester
What is the percentage of triacylglycerols in chylomicrons?
What is the percentage of triacylglycerols in VLDL?
What is percentage of cholesteryl esters in LDL?
What are apolipoproteins of plasma lipoproteins?
Not just Structural proteins, many are enzymes or coactivators of enzyme
Where are chylomicrons synthesised in?
synthesised in ER of enterocytes
Where is chylomicrons released into?
released into lymphatic system
When is the chylomicrons released into lymphatic system?
Before entering the circulation, detected in circulation 1 - 2 hour after meal
What does the Nascent Chylomicrons contain?
Contain apoB48 but acquire apoA, C and E from DHL
What is chylomicrons comprised of?
Mainly of TG (80-90%)
What is the major function of chylomicrons?
Transport dietary TAGs from gut to tissues (liver, skeletal and cardiac muscle and adipose tissue)
What does blood plasma after a meal?
Turbidity (milk appearance) due to presence of large numbers of chylomicrons which transport lipids absorbed in gut to liver and other tissues
What are chylomicrons Triglyceride hydrolysed by?
By enzyme lipoprotein lipase (LPL)
[LPL hormonally regulated]
What is required for activation of LDL?
What does the dietary TAG in the tissue do?
Adipose tissue - storage
Skeletal/cardiac muscle - oxidised
Liver takes up glycerol and MAG
What is found on the luminal surface of endothelial cells?
LpL that escapes degradation will be picked up by HSPGs and VLDL receptors on the basal surface of overlying endothelial cells
What tissue is the HSPC receptors found on the endothelial cells?
1) Adipose tissue
2) Skeletal and cardiac muscle
3) Lactating mammary gland
What is the process of chylomicron remnants?
TG hydrolysis reduce size and density of particle - chylomicron remnants -> apolipoproteins, variable amount of TAGs, PL, CE, MAG
How is chylomicron remnants taken by liver?
Taken up by live by receptor mediated endocytosis (through LDL receptor and it is ApoE dependent)
What would happen to the FA produced?
FA may be re-esterified to make TGs which may be sent to adipose tissue for storage or to peripheral tissues to be utilised
What does VLDL do?
Transport mainly TGs from liver to adipose tissue (storage) or peripheral tissues (utilisation)
What does Nascent VLDL contain?
Contain apoB100 but acquire others (apo A, C and E) from HDL
How is VLDL TGs hydrolyse?
By LPL forming VLDL remnants (IDL)
What happens to the 50% VLDL remnants?
recycled in liver - requires apoE
What happens to the remainder of the VLDL remnants?
converted into LDL
When is LDL formed?
From IDL(intermediate lipoprotein) after
1) CL(cholesterol)/CE (cholesterol ester) content of IDL enriched (and TG depleted) by exchange with HDL of TG for CL/CE
2) some Apo's (except B100) transferred to HDL
What does LDL?
Major cholesterol carrier to peripheral tissues
Where does the LDL get transported to?
1) Approx. 40% transported to tissues which require CL for biosynthesis (e.g. steroid hormones)
2) Approx. 60% taken up by liver by receptor mediated endocytosis and recycled
What is the percentage of TG, PL, CL+CE in VLDL?
TG: 50 - 60%
PL: 15 - 20%
CL+CE: 15 - 25%
What is the percentage of TG, PL, CL+CE in LDL?
TG: 5 - 10%
PL: 15 - 20%
CL+CE: 40 - 50%
What is the percentage of TG, PL, CL+CE in HDL?
TG: 3 - 5%
PL: 20 - 35%
CL+CE: 15 - 20%
What is the shape of high density lipoproteins?
Heterogenous collection of particles of slightly varying size/density (HDL 1 -4)
What is the major function of HDL?
1) Transport cholesterol from tissues to liver for disposal (reverse cholesterol transport)
2) Acts as source of these apolipoproteins in maturation of other lipoproteins
What does HDL contain?
Contain multiple apolipoproteins (A, C, E)
What is HDL associated with?
as many as 15 different proteins other than apolipoproteins
- LCAT (lecithin cholesterol acyltransferase)
- PTLP (phospholipid transfer protein)
What does a LDL contain?
2) Unesterified cholesterol
3) Apoprotein B-100
4) Cholesteryl ester
How is cholesterol stored?
In lipid droplets in cytoplasm and converted to cholesterol esters (LCAT)
Where is cholesterol most abundantly found?
In steroidogenic tissue example in adrenal glands and gonads
What happens when there is cholesterol excess, where is it stored?
Cholesterol rich lipid droplets may be found in other tissue
What is a clinical condition relating to cholesterol?
What is Familial Hypercholesterolemia?
1) mutations of LDL receptor or ApoB100 genes
2) hepatic uptake of LDL absent or impaired
3) grossly elevated plasma cholesterol
What type of disorder is familial hypercholesterolemia?
Autosomal dominant disorders
How do you manage Familial Hypercholesterolemia?
1) Diet and lifestyle changes
2) Statins combined with bile acid sequestrants, ezetimibe or niacin
3) LDL apheresis (selective removal of LDL)
What is the symptoms of in familial hypercholesterolemia?
LDL > 200 mg/dl, accelerated CAD, MI by age 30 - 40
Atheromas at multiple sites
Canoes and articular xanthomas
What is the clinical correlations with LDL and Atherogeneisis?
Excess LDL can accumulate in intimate of blood vessel
- oxidised LDL antigenic/pro-inflammatory
- macrophage infiltration of intima
What happens when there is an excess LDL?
1) Macrophage take up oxLDL by a 'scavenger receptor' mechanism (foam cells) and create 'fatty streak'
2) Chronic inflammatory state in vessel wall, with increased recruitment of inflammatory cells, VSMC and fibroblast proliferation and endothelial cell dysfunction
3) Plaque formation, rupture and thrombus formation
Where are triglycerides stored in?
In dedicated energy depots in adipocytes
What are triglycerides?
Highly reduced (energy dense) form of carbon
What is the energy content of food constituents in triglycerides?
Carbohydrate: 16 kJ/g
Fat: 37 kJ/g
Protein: 17 kJ/g
What is a property of triglyceride?
No solvation/anhydrous (more compact than CHO)