cholestrol Flashcards
what three sources are fats derived from
.the diet
.de nova biosynthesis (liver)
.storage depots in adipose tissues (fats broken by lipases)
where are bile salts generated and stored
generated: liver, stored:gallbladder
describe how bile salts work starting from during digestion
during digestion, bile salts pass from the BILE DUCT into the intestine
Emulsify fats aiding their digestion of fats and fat soluble vitamins, A,D,E,K.
What happens if there is a lack of bile salts?
.Fat passes through gut undigested and unabsorbed hence STEATORRHEA. (FATTY STOOL)
What is orlistat?
an inhibitor of GASTRIC and PANCREATIC lipases chemically synthesised from lipstatin derivatives (a product of Streptomyces toxytricini)
what are the concequences of taking tetrahydrolipstatin (orlistat)- a drug used to treat obesity.
.abdominal pain
.urgency to defecate
.increased flatus
.steatorrhea
i am found in the intestines and my role is dietary fat transportation. What lipoprotein am I?
Chylomicron
describe source and role of VLDL
Liver, Endogenous fat transport
describe source and role of IDL
VLDL, LDL precursor
describe source and role of LDL
IDL, cholestrol transport
describe source and role of HDL
LIVER, reverse cholesterol transport
Describe the anatomy of chlyomicrons
.Digested dietary products are absorbed via enterocytes lining brush border of the small intestine
. Triglycerides are resynthesized under control of enzymes before incorporation into chylomicrons
. Chlyomicrons are transported via lymphatics into blood stream
.CM’s aqquire apoproteins from HDL following release into bloodstream
Chylomicrons travel from the …… of the intestine to the …… and to the …. where they enter the bloodstream
lacteals, thoracic duct, left subclavian vein
Where is lipoprotein lipase located
capillary endothelial cells where lipase lines a variety of tissues incl. adipose, heart and skeletal muscle
All physiological requirements for cholesterol are supplied by the …. through …. synthesis of cholesterol from …..
liver, de nova , acetyl co A
what is cholesterol in one word
a steroid
Summarise the three key parts of cholesterol synthesis
.Synthesis of isopentenyl pyrophosphate, an activated isoprene unit which serves as a key building block (cytoplasm).
.Condensation of six molecules of isopentenyl pyrophosphate to form squalene (cytoplasm).
.Cyclisation and demethylation of squalene by monooxygenases to give cholsterol (ER).
Give the first three stages of cholesterol synthesis
. 2 Acetyl Co-A undergo condensation to form Acetoacetyl co A
.Acetoacetyl co A +acetyl Co A ———>HMG-coA (condensation)
.HMG co A reduced to mevalonate
what enzyme reduces HMG co A into mevalonate.
HMG Co A reductase
Mevalonate undergoes sequential ……. at the hydroxyl groups at position ……….. ,followed by decarboxylation to form …..
phosphorylation, 3,5, 3-isopentyl pyrophosphate.
what is dolichol phopsphate
Dolichol phosphate is a specialized lipid molecule located in the ER membrane and involved in N-linked glycosylation of proteins.
how is squalene synthesised from 3-isopentyl pyrophosphate
Via an isomerization reaction, Dimethylallyl pyrophosphate can be produced from isopentyl PP.
This can condense with a unit of Isopentenyl-PP to form the C10 compound Geranyl-PP.
A third isopentenyl-PP molecule is added to form the C15 intermediate farnesyl-PP.
Two farnesyl-PP molecules condense to form C30 squalene plus 2 molecules of pyrophosphate.
give the three steps for cylisation of squalene into cholestrol.
.Squalene is first reduced in the presence of oxygen and NADPH to form squalene epoxide which has a different C=C bond distribution priming the molecule for carbon ring fusion.
The enzyme squalene epoxide lanosterol-cyclase catalyses the formation of Lanosterol. A series of 1,2-methyl group and hydride shifts along the chain of the squalene molecule result in the formation of the four rings.
Demythelation of lanosterol (three methyl grps) to give cholesterol.
what precursor is generated from cholesterol?
pregnenolone (21 carbons)
what enzyme generates pregnenolone from cholesterol?
desmolase
what 5 classes of steroid hormones come from pregnenolone?
Progestagens (C-21), Glucocorticoids (C-21), Mineralcorticoids ( C-21), Androgens (C-19), Estrogens ( C-18)
what is calcitrol?
a key part of vit. D aiding in calcium metabolism
what are the two primary bile salts cholestrol is converted into?
glycocholate, taurocholate.
How+ where are cholesterol esters formed?
.In the plasma from cholesterol and phosphatidylcholine ( acyl chain lecithin) catalysed by LCAT
LCAT=Lecithin cholesterol acyltransferase
Familial hypercholesterolaemia (FH) is inherited as a ……… …….. trait
monogenic dominant
indicate two concequences of FH
atherosclerosis, coronary infarcts
how do statins work
. Inhibits HMG co A reductase hence inhibiting cholestrol synthesis
name two statins
Lipitor, Crestor
what are resins/sequestrants?
Resins bind/sequester bile acid-cholesterol complexes preventing their reabsorbtion by the intestine.
increases hdl and decreases LDL.
name a resin
Cholestyramine ( brand Questran, prevalite)
