Lipid Flashcards
Digestion
6
1- the main lipid in diet is TAG ( 90%) and also there is phospholipids, cholesterolester and fat soluble vitamins
2- digestion of dietary lipid starts in stomach by gastric lipase
3- emulsification happens in small intestine by the help of bile salts and mixing by the help of peristalsis
4- emulsification increases the surface area of hydrophobic micelles for the digestive enzymes to affect on it
5- degradation of lipid happens by pancreatic enzymes ( pancreatic lipase that digest TAG to 2 monoacylglcyerol by separating of 1,3 f. A in TAG)
( phopholipase A2 that digest P.L to lysophospholipid by separation of the f.a from second position) ( cholesterol ester hyrolase that separate cholesterol from f.a)
6- pancreatic lipase is activated by Co lipase , Ca and bile salts
Absorption
1- medium and short f.a chain are absorbed to enterocytes without assistance with mixed micelles and transported to blood where they are carried by serum albumin to liver
2- f. A , cholesterol, lysophopholipid , 2- monoacylglycerol and fat soluble vitamins form micelles to facilitate transport to enterocytes membrane
3- in the enterocytes, they are reformed and recreated in form of CM
4- because its large size , CM can’t be transported to blood directly so it goes to lymphatic system , thoracic duct, SVC , heart then to systemic circulation
5- lipoprotein lipase
• secreted from vascular endotheliam and heparin
• activated by apo 2 and insulin
• digest TAG to glycerol and f.a
• called clearing factor
Talk about Steatorrhea ( def - causes)
Prescence of fat in stool , it appears bulky and pale with greasy consistency and foul smelling
Its due to a problem in either absorption or digestion
1- deficiency of pancreatic lipase due to pancreatitis or pancreactomy
2- hepatitis , or cholecystitis or bile duct obstruction
3- diseases in intestinal mucosa cells that prevent absorption of lipid
Inhibitors of lipid digestion and absorption
1- green tea
2- orlistats ( lipase inhibitor)
3- grape seed ( lipase inhibitor)
4- pectin that prevent lipid absorption
De novo synthesis of f.a
- def
- location
- requirements
1- saturated fatty acid synthesis by acetyl CoA to give palmitic acid( 16 c)
2- cytosol in liver , kidney adipose tissue etc except RBC( there no mitochondria for acetyl CoA synthesis from pyruvate)
3- cytosolic acetyl CoA
- 2 NADPH+H
- FAS
- ACC
Steps of de novo generation of f.a
Primary steps ( pre steps)
1- formation of cytosolic acetyl CoA
Acetyl CoA is formed in mitochondria and can’t cross the cytosol so it reacts with OAA to give citrate by citrate synthase and then citrate passes to cytosol in exchange with malate and after that it is cleaved to acetyl CoA and OAA by ATP citrate liase and this is called citrate shuttle
Acetyl CoA is used in palmitic acid synthesis
, OAA is converted to malate by MD and malate is converted to pyruvate by malic enzyme giving NADPH used in palmitic acid synthesis
2- formation of malonyl CoA
• 8 acetyl CoA are needed, 7 are converted to malonyl CoA by ACC with its co enzyme ( biotin with ATP) and Co2
3- FAS
• acetyl CoA is the primary unit in f.a synthesis
• f.a synthesis is catalyst by FAS
• it is multi enzyme ( dimer) and the one monomer is composed of seven enzymes arranged from head to tail in the 2 monomers (( عكس بعض )) plus a domain covalently bind a molecule of 4 phosphopantetheine that carries acyl units on its SH group during synthesis ( there is sh group at the 2 ends of each monomer
What is the rate limiting enzyme in de novo generation of f.a
ACC
Regulation of ACC
Short term
• allosteric effect : it is activated by citrate ( source fir acetyl coa) and inhibited by palmitic acid ( product inhibition) ( convert it from active polymer to inactive dimer)
• covalent modification
DePhosphorylated form is the active form thus glocagon and epinephrine inhibit it and insulin activates it
Long term
• gene expression
Insulin up regulates it to more ACC synthesis
and vice versa
+ calorie or + carb diet increases the synthesis of ACC and - calorie or + fat diet inhibites it
Fate of palmitic acid
1- chain elonation : to form a longer f.a
2- desaturation : may undergo desaturation in C9-C10 to form palmitoleic acid
3- formation of p.l
4- formation of sphingosine base
5- its usual fate is esterification into acyelglycerol or cholesterol ester
Sources of NADPH ( very important)
1- HMP in cytosol , it is the major source
2- malate to pyruvate by malic enzyme
3- cytoplasmic isocitrate dehydrogenase, it is a minor source
Synthesis of TAG
- site
- organelle
- source of f.a
1- in most tissues but predominantly in liver adupose tissue and intestinal mucosa and mammary gland
2- endoplasmic reticulum
3- de novo ir from diet
Steps of TAG synthesis
1-Activation of fatty acid by attaching it to CoA to form acyel CoA by aceyl CoA synthatase ( T= 2ATP) or thiokinase
2- activation of glycerol by converting it to glycerol 3 p by 2 ways
- glycolysis until DAHP formation then converted to glycerol 3 p by glycerol 3 p dehydrogenase ( linkage between glycolysis and lipogensis)
- glycerol kinase that phosphorylate it to glycerol 3 p but it is found in liver , not adipose tissue
Fate of TAG
It is stored either in
1- it is stored in form of fat droplets in cytosol in white adipose tissue in
• subcutaneous depots eg in gluteal region
• viesral
2- it is stored in liver and exported by VLDL to peripheral tissues , excess accumulation of TAG in liver leads to fatty liver
