Cholesterol Flashcards
Where are bile salts generated and stored
Made in liver and stored in gall bladder
Orlistat
Inhibitor of gastric and pancreatic lipases
Reduces fat absorption by 30%
Almost all excreted by faecal route
Can cause abdominal pain urgency to defeccate and increased callus and steatorrhea
Steatorrhea
Fatty stool. Lack of bile salts means majority of fat passes through
Bile salts purpose
Digest fats and help absorb fat soluble vitamins
Lipoprotein
Lipids are transported by lipoproteins
Chylomicrons location and role
Found in intestine
Dietary fat transport
Very low density lipoprotein location and functional
Liver
Endogenous fat transport
Intermediate density lipoprotein location and role
VLDL
LDL precursor
Low density lipoprotein location and function
IDL
Cholesterol transport
High density lipoprotein location and role
Liver
Reverse cholesterol transport and takes lipid back to the liver to be broken down into bile salts
Chylomicrons
Where triglycerides are incorporated
They acquire apoproteins from HDL following release into bloodstream
They transport triglycerides and cholesterol
Apoproteins
A protein that combines with a prosthetic group to form a conjugated protein
Lipoprotein lipase
Degrades circulating triglycerides
Located on capillary endothelial cells lining adipose heart and skeletal muscle
Cholesterol
Large non polar steroidal structure.
Increased or decreases membrane stiffness depending on temperature and nature of membrane
Sources of cholesterol
Dietary intake limited to 500mg
Denovo synthesis-most if physiological requirements fulfilled through this
Deposition in adipose tissue
Cholesterol biosynthesis steps
1) synthesis of isopentynyl pyrophosphate
2) condensation of 6 molecules of isopentynyl pyrophosphate to make squalene
3) cyclisation and demethylation of squalene by monooxygenases to make cholesterol
Steroid hormone formation
Cholesterol makes pregnenolone making progestagens which split into glucocorticoid mineralcroticoid and androgens
Vitamin d synthesis
Exposure of skin to sun needed
7-dehydrocholesterol in the presence of UV makes previtamin D3 which is converted to vitamin D3 which then makes calcitriol
2 bile salts
Glycocholate and taurocholate
Hypercholesterolaemia
Due to elevated LDL levels
Mono genic autosomal dominant
Patients within homozygous FH had a serum LDL 5 times more than normal, premature ASCVD,xanthomas
Patients with heterozygous FH have less severely elevated LDL ~2/3 times greater
Pathogenesis
Mutations in LDL-R gene result in Poor LDL uptake into peripheral tissues
How do statins inhibit cholesterol
As it is a competitive inhibitor of HMG-CoA reductase
This prevents conversion of HMG-CoA to mevalonate thus reducing cholesterol
