cholestrol

Question 1

what three sources are fats derived from

Answer 1

.the diet
.de nova biosynthesis (liver)
.storage depots in adipose tissues (fats broken by lipases)

Question 2

where are bile salts generated and stored

Answer 2

generated: liver, stored:gallbladder

Question 3

describe how bile salts work starting from during digestion

Answer 3

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.

Question 4

What happens if there is a lack of bile salts?

Answer 4

.Fat passes through gut undigested and unabsorbed hence STEATORRHEA. (FATTY STOOL)

Question 5

What is orlistat?

Answer 5

an inhibitor of GASTRIC and PANCREATIC lipases chemically synthesised from lipstatin derivatives (a product of Streptomyces toxytricini)

Question 6

what are the concequences of taking tetrahydrolipstatin (orlistat)- a drug used to treat obesity.

Answer 6

.abdominal pain
.urgency to defecate
.increased flatus
.steatorrhea

Question 7

i am found in the intestines and my role is dietary fat transportation. What lipoprotein am I?

Answer 7

Chylomicron

Question 8

describe source and role of VLDL

Answer 8

Liver, Endogenous fat transport

Question 9

describe source and role of IDL

Answer 9

VLDL, LDL precursor

Question 10

describe source and role of LDL

Answer 10

IDL, cholestrol transport

Question 11

describe source and role of HDL

Answer 11

LIVER, reverse cholesterol transport

Question 12

Describe the anatomy of chlyomicrons

Answer 12

.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

Question 13

Chylomicrons travel from the …… of the intestine to the …… and to the …. where they enter the bloodstream

Answer 13

lacteals, thoracic duct, left subclavian vein

Question 14

Where is lipoprotein lipase located

Answer 14

capillary endothelial cells where lipase lines a variety of tissues incl. adipose, heart and skeletal muscle

Question 15

All physiological requirements for cholesterol are supplied by the …. through …. synthesis of cholesterol from …..

Answer 15

liver, de nova , acetyl co A

Question 16

what is cholesterol in one word

Answer 16

a steroid

Question 17

Summarise the three key parts of cholesterol synthesis

Answer 17

.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).

Question 18

Give the first three stages of cholesterol synthesis

Answer 18

. 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

Question 19

what enzyme reduces HMG co A into mevalonate.

Answer 19

HMG Co A reductase

Question 20

Mevalonate undergoes sequential ……. at the hydroxyl groups at position ……….. ,followed by decarboxylation to form …..

Answer 20

phosphorylation, 3,5, 3-isopentyl pyrophosphate.

Question 21

what is dolichol phopsphate

Answer 21

Dolichol phosphate is a specialized lipid molecule located in the ER membrane and involved in N-linked glycosylation of proteins.

Question 22

how is squalene synthesised from 3-isopentyl pyrophosphate

Answer 22

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.

Question 23

give the three steps for cylisation of squalene into cholestrol.

Answer 23

.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.

Question 24

what precursor is generated from cholesterol?

Answer 24

pregnenolone (21 carbons)

Question 25

what enzyme generates pregnenolone from cholesterol?

Answer 25

desmolase

Question 26

what 5 classes of steroid hormones come from pregnenolone?

Answer 26

Progestagens (C-21), Glucocorticoids (C-21), Mineralcorticoids ( C-21), Androgens (C-19), Estrogens ( C-18)

Question 27

what is calcitrol?

Answer 27

a key part of vit. D aiding in calcium metabolism

Question 28

what are the two primary bile salts cholestrol is converted into?

Answer 28

glycocholate, taurocholate.

Question 29

How+ where are cholesterol esters formed?

Answer 29

.In the plasma from cholesterol and phosphatidylcholine ( acyl chain lecithin) catalysed by LCAT
LCAT=Lecithin cholesterol acyltransferase

Question 30

Familial hypercholesterolaemia (FH) is inherited as a ……… …….. trait

Answer 30

monogenic dominant

Question 31

indicate two concequences of FH

Answer 31

atherosclerosis, coronary infarcts

Question 32

how do statins work

Answer 32

. Inhibits HMG co A reductase hence inhibiting cholestrol synthesis

Question 33

name two statins

Answer 33

Lipitor, Crestor

Question 34

what are resins/sequestrants?

Answer 34

Resins bind/sequester bile acid-cholesterol complexes preventing their reabsorbtion by the intestine.
increases hdl and decreases LDL.

Question 35

name a resin

Answer 35

Cholestyramine ( brand Questran, prevalite)