Lipids Flashcards
Lipids classification
Fatty acids
Vit fat soluble ( A,E,K,D)
Phospholipids
Amphipatics :
Sphingolipids
Triacylglycerol
Glycolipids
Triacylglycerol structure
3 fatty acids
Types of triacylglycerol in natural oils
Unsaturated FAs
Primary target of salivary lipase
Fewer than 12C tTAGs
Solid fats composed mostly of
Saturated fats
Calories of fat per gram
9
Functions of fats
Structure of cells Enzyme cofactor Vision Digestion Anti oxidant
Daily fat consumption average
60-160g
Thé 2 essential dietary fatty acid
Linoleic acid which gives arachidonic acid
a-linolenic acid
Bile acid production rate limiting step
Cholic acid synthesis
Bile acid synthesis pathway
Cholesterol to cholic acid
Bile salts formation location
Liver
Pancreatic lipase action on TGs
Break it down to 2-monoacylglycerol
And free fatty acids at carbon 1 and 3
When is stored fat used ?
When there’s non availability or inadequacy of carbohydrates or the impossibility of metabolizing them for energy
What hormone ca activate lipase?
Glucagon
Epinephrine
Nor epinephrine
How can insulin inhibits lipase activity
Insulin promotes dephosphorylation of lipase by cAMP and PKA inhibition
Acetyl coa carboxylase in fatty acid synthesis is inhibited by …
Hormone mediated phosphorylation so cAMP activation inhibits it
Rate limiting step in fatty acids synthesis
Acetyl coa carboxylase
How are fatty acids transported into blood
Serum albumin
Fate of glycerol produced by TGs degradation
Goes to liver
Converted to dihydroxyacetone phosphate by glycerol kinase
Fate of fatty acids after activation
Can be broken down to form CO2
Can be used to produce TGs
Activation of fatty acids done by
Acyl coa synthétase
Where does fatty acid activation occur
Outer mitochondrial membrane
Product of fatty acid activation
Acyl Coa
Transport of acyl coa into mitonchondria ( less than 12c)
Passive diffusion
Transport of acyl coa into mitonchondria ( more than 12c)
Acyl coa converted to acyl carnitine and converted back to acyl coa once inside
Done by carnitine acyltransferase I (outer) and II (inner)
Disease related to carnitine synthesis , transfer ease etc causes
Muscle cramping
Severe muscle weakness especially in exercise
Death
Fatty acid oxidation regulation
Malonyl coa can inhibit carnitine acyl transferase I
Goal of fatty acid oxidation
Break down of fatty acid produce ATP
Acetyl coa formes can enter citric cycle producing even more ATP
Beta oxidation pathway
Fatty acid converted to trans-enoyl -CoA by acyl Coa dehydrogenase
FADH2 PRODUCED
Trans-enoyl -coa converted to L-B-hydroxylacyl-CoA by enoyl coa hydratase
l-b-hydroxyacyl-COa converted to B-ketoacyl-CoA by B-hydroxyacyl-coa dehydrogenase
NADH PRODUCED
B-ketoacyl-CoA converted to acetyl-coa and fatty acids (less 2 carbons)
ATP production per cycle of fatty acid oxidation
1 NADH
1 FADH2
1 Acetyl coa which goes to citric cycle
So that’s 2.5+1.5+10= 14 ATP
Do you use ATP during fatty acid activation?
Yes 2 ATP
Goal of fatty acid oxidation in peroxisomes
Breakdown of very long fatty acids (more than 22 carbons)
X- adrenoleucodystrophy
Disease due to defect of ALD protein transport which lead to accumulation of long chain fatty acids because they can’t get to peroxisomes.
They destroy myelin and lead to death by 10 yo
Zellweger syndrome
Defect in peroxisome preventing breakdown of long chain fatty acid
Liver, kidney and muscles abnormalities
Death by 6yo
Products of odd chain fatty acid alpha oxidation
Proprionyl CoA
Fate of propionyl from odd fatty acid alpha oxidation
Peopionyl Coa converted to succinyl coA thanks to vitB12
Oxidation of monounsaturated fatty acid
enoyl coa isomerase convert the unsaturated fatty acid with cis configuration to trans enoyl coa
The rest of oxidation continue as usual
Oxidation of polyunsaturated fatty acids
2,4 dienoyl coa reductase convert the 2,4 dienoyl coa to cis enoyl coa ( monounsaturated)
Enoyl coa isomerase convert cis enoyl coa to trans enoyl coa.
Rest of oxidation continue as usual
Alpha oxidation location
Peroxisomes
Oméga oxidation
Starts at methyl group
Occurs in smooth ER for part of cyt p450 pathway
Médium chain length FAs
No energy produced
Produce dicarboxylic group which when processed by beta oxidation produce succinate and adipate
Precursors of fat production
Carbohydrate
Protein
Location of de novo fatty acid synthesis
Cytosol
Fatty acid synthesis committed step
Acetyl coa converted to Malonyl coa by Acetyl coa carboxylase
Intermediate used to transport acetyl coa into cytosol for fatty acid synthesis
Citrate
Acetyl coa carboxylation step to form malonyl coa
Carboxy biotin intermediate give activated CO2 to acetyl coa to form malonyl coa
Fatty acid synthesis spiral
Acyl carrier protein ACP bien malonyl coa and acetyl coa
Formation of acetylACP and malonylACP
Condensation reaction
Réduction réaction
Dehydration reaction
Reduction
Fatty acid oxidation carrier
Coa
Fatty acid synthesis carrier
ACP
Is there bicarbonate dépendance in fatty acid synthesis
Yes - carbon dioxide donor
Major lipid in body
Acylglycerols
TGs synthesis precursors
L-glycerol 3 pi
Fatty acyl coa
Source of l glycerol 3 pi
Dihydroxyacetone phosphate reduced to L glycerol 3 pi
In liver only, glycerol from TGs degradation can be act on by glycerol kinase to form glycerol 3 pi
Reduction of dihydroxyacetone pi occurs in
Liver and adipose tissue
Adipocyte Only take up Glucose in the presence of insulin
True or false
True
Fatty acyl activation before TGs synthesis
FA activated by coa addition
Leads to fatty acyl coa synthesis
TGs synthesis mechanism
2 fatty acyl coa added to glycerol 3 pi at carbon 1 and 2 by glycerol phosphate acyltransferase
Gives phosphatidic acid
Phosphatidic acid hydrolyzed by phsphatidate phosphatase and gives diacylglycerol
Diacylglycerol reacts with 3rd fatty acid and gives TG Via diacylglycerol acyltransferase
Phospholipids structure
L glycerol 3 pi with 2 hydroxyl group estérifier to fatty acids
Last groups estérifies to phosphoric acid
Major classes of phospholipids
Glycerol backbone
Sphingosine backbone
Most abundant phospholipids in plants and animals
Phosphatidylcholine
Phosphatidylethanolamine
Phosphatidyl serine
Phospholipase A1 act on ..
FA at carbon 1
A2 phospholipase act at
FA at carbon 2 of phospholipid
C phospholipase act at
Before phosphate of phospholipid
D phospholipase act at
After phosphate of phospholipids
Phospholipase A2 role
Releases arachidonic acid from phosphotidylinositol to produce PG
2 strategies of phospholipid synthesis
Diacyglycerol formed like in TGs synthesis activated by CDP which can then be replaced on molecule by polar head group
Or
CDP already bound to head group
Head group activated transferred to diacylglycerol giving the phospholipid
Phosphatidylinsolitol serves as reservoir of
Arachidonic acid
Which one is more hydrophobic
A . Cholesterol
B. Cholesteryl ester
B
2 major sources of cholesterol in body
Dietary cholesterol
Cholesterol synthesized in extrahepatic tissues
De Novo synthesis from liver
Route for Dietary cholesterol to liver
Chylomicron remnants
Route for cholesterol synthesized in extraaheparic tissues to liver
HDL route
Major fate of cholesterol
Secretion of VLDL
cholesterol secreted in bile
Cholesterol converted to bile acids
Major sites of cholesterol synthesis
Liver and intestine 80%
Other sites of cholesterol synthesis
Adrenal cortex
Reproductive tissue LIKE OVARIES AND TESTES
Biosynthesis of cholesterol
(I)
2 Acetyl CoA —> acetoacetyl CoA
Enzyme : thiolase
(II)
Acetoacetyl CoA + acetyl CoA —> HMG-CoA
Enzyme : HMG
(III)
HMG CoA —> mevalonate
Enzyme : HMG-CoA reductase
NADPH used , CoA released
3 steps later , squalene is formed
Squalene gives lanosterol which gives cholesterol
2 forms of HMG CoA synthase isoenzymes
Cytosolic form for cholesterol synthesis
Mitochondrial form for ketone body synthesis
Rate limiting step in cholesterol synthesis
HMG CoA reductase
Is HMG CoA reductase reversible or irreversible
Irreversible
Regulation of HMG CoA reductase
High cholesterol inhibits enzyme
Inactive When enzyme phosphorylated
HMG COA pi —-> HMG CoA
Done by phosphatase
Phosphatase activated by insulin and inhibited by glucagon
AMP kinase can give the inactive form
How is cholesterol eliminated in humans
Conversion to bile acids and bile salts
What drugs are used in high plasma cholesterol
Statins (atorvastatin, lovastatin, simvastatin)
How do statins help in decreasing cholesterol level
Act as analog of HMG CoA and competitively inhibit HMG CoA reductase
Where are bile salts synthesized
Liver
Primary bile acids
Cholic acid
Chenodeoxycholic acid
Bile acid found in largest amount in bile
Cholic acid
Fate of primary bile acids
Converted to glycine or taurine
Lipoproteins functions
Transport of fat soluble substance
Type of lipoproteins
Chylomicrons
VLDL
LDL
HDL
Lipid part of lipoproteins
Depends on type of lipoproteins
Protein part of lipoproteins
Apolipoproteins
Lipoproteins classification
HDL (33% protein )
LDL
IDL
VLDL
Chylomicrons (1-2% proteins )
Functions of apoproteins
Structural Components
Enzyme cofactors
Ligands for interaction with lipoprotein receptors in tissues
Major apo lipoprotein in HDL
APO- A1
also found in chylomicrons
Major chylomicrons apo lipoproteins
Apo-B48
Major LDL apo lipoproteins
Apo-B100
also found in VLDL
Apo c2
Found in HDL, chylomicron’s and VLDL
Serve as cofactor for lipoproteins lipase
Apo E
Found in chylomicron remnants , VLDL, IDL, HDL
Ligand used for interaction with tissue lipoprotein receptor
3 major pathways of lipid transport
Exogenous pathway (dietary lipids to tissues )
Endogenous pathway ( lipids from liver to tissues )
Reverse cholesterol transport pthway ( cholesterol in tissues to liver )
Lipids and proteins proportion in chylomicrons
High percentage of lipid
Low protein percentage
Chylomicrons lipid transport pathway
Exogenous lipid transport
Lipoprotein responsible for milky appearance of plasma after meal
Chylomicrons
Iipoproteins responsible for transport of cholesterol to liver
Remnants of chylomicrons
Chylomicron pathway
Chylomicron carry dietary fats
Chylomicron acquire apo CII and apo E from HDL
Chylomicron complex meet lipoprotein lipase and removal of TGs and chylomicrons remnants released
Chylomicron remnants transport cholesterol to liver where apo E binds receptor on liver for delivery
Where can you find lipoprotein lipase
Anchored to capillary wall of tissues ( adipose, cardiac, skeletal)
Is there LPL in liver ?
No
VLDL function
Transport TAGs from liver to target tissues
Endogenous pathway of lipid transport
B100 helps form export VLDL
VLDL get apo CII, apo E From HDL
VLDL interacts lipoprotein lipase producing LDL
LDL goes to tissue where B100 binds receptors
LDL gets into cell and deliver cholesterol
IDL fate
Converted to LDL
Direct uptake by liver
Primary carrier of cholesterol for delivery to tissues
LDL
With highest half life
How is the uptake of LDL done ?
Receptor mediated endocytosis
Cholesterol uptake fats
Cholesterol incorporated into membrane
Repression of cholesterol synthesis
Stimulate of cholesterol storage
Repression of LDL receptor synthesis
Reverse cholesterol transport pathway
Nascent HDL from liver with low lipid level
HDL circulâtes in blood and picks up cholesterol
HDL goes back to liver with cholesterol
Functions of HDL
Reservoir of apolipoproteins necessary for other lipoproteins
Uptake of cholesterol- excellent acceptors of cholesterol
Enzyme responsible for estérification of free cholesterol
Lecithin cholesterol acyltransferase (LCAT)
What happens if Chosteryl ester present in HDL
HDL can’t get back to cell
How is damaged LDL called
OxLDL
What happens if elevated oxLDL
Increased monocytes adhésion leading to Marcel phases engulfing the oxLDL by endocytosis => form FOAM cells
Benefits of HDL
Absorbs most of cholesterol in extra hepatic tissues “cholesterol sponge”
Unloads CE to liver
Degrades oxLDL
Does increase lipoproteins especially LDL can lead to atherosclerosis?
Yes
Source of hormones
Cholesterol
Dyslipoproteinemia
Abnormal lipoproteins in blood
Primary dyslipoproteinemia
Hyper synthesis or hypodegradation of lipoproteins due to enzyme deficiency
Secondary lipoproteinemia
Complication of another conditions Like : Extrahepatic obstruction Exogenous sex hormones (oral pill) Steroids Diabetes mellitus Biliary cirrhosis Hypothyroidism Alcohol consumption Obesity Thiozide diuretics
Fredickson classification Of lipid disorders
Type I dyslipidemia
Type IIa dyslipidemia
Type IIb dyslipidemia
Type III
Type IV.
Type I dyslipidemia
Decreased lipoproteins lipase
Increased TGs so increased chylomicrons
Cause :
pancreatitis (TGs obstruction)
Éruptive xanthomas
Lipemia retinalis
Type IIa lipidemia ( familial hypercholesteremia)
Familial
Young death if homozygous ( less than 20)
LDL receptor gene defect or absent
LDL cholesterol increased
Causes :
Type IV familial combined hyperlipidemia
Obesity and insulin resistance common
