cholestrol Flashcards

1
Q

what three sources are fats derived from

A

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

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2
Q

where are bile salts generated and stored

A

generated: liver, stored:gallbladder

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3
Q

describe how bile salts work starting from during digestion

A

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.

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4
Q

What happens if there is a lack of bile salts?

A

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

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5
Q

What is orlistat?

A

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

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6
Q

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

A

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

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7
Q

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

A

Chylomicron

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8
Q

describe source and role of VLDL

A

Liver, Endogenous fat transport

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9
Q

describe source and role of IDL

A

VLDL, LDL precursor

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10
Q

describe source and role of LDL

A

IDL, cholestrol transport

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11
Q

describe source and role of HDL

A

LIVER, reverse cholesterol transport

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12
Q

Describe the anatomy of chlyomicrons

A

.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

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13
Q

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

A

lacteals, thoracic duct, left subclavian vein

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14
Q

Where is lipoprotein lipase located

A

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

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15
Q

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

A

liver, de nova , acetyl co A

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16
Q

what is cholesterol in one word

17
Q

Summarise the three key parts of cholesterol synthesis

A

.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).

18
Q

Give the first three stages of cholesterol synthesis

A

. 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

19
Q

what enzyme reduces HMG co A into mevalonate.

A

HMG Co A reductase

20
Q

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

A

phosphorylation, 3,5, 3-isopentyl pyrophosphate.

21
Q

what is dolichol phopsphate

A

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

22
Q

how is squalene synthesised from 3-isopentyl pyrophosphate

A

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.

23
Q

give the three steps for cylisation of squalene into cholestrol.

A

.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.

24
Q

what precursor is generated from cholesterol?

A

pregnenolone (21 carbons)

25
what enzyme generates pregnenolone from cholesterol?
desmolase
26
what 5 classes of steroid hormones come from pregnenolone?
Progestagens (C-21), Glucocorticoids (C-21), Mineralcorticoids ( C-21), Androgens (C-19), Estrogens ( C-18)
27
what is calcitrol?
a key part of vit. D aiding in calcium metabolism
28
what are the two primary bile salts cholestrol is converted into?
glycocholate, taurocholate.
29
How+ where are cholesterol esters formed?
.In the plasma from cholesterol and phosphatidylcholine ( acyl chain lecithin) catalysed by LCAT LCAT=Lecithin cholesterol acyltransferase
30
Familial hypercholesterolaemia (FH) is inherited as a ......... ........ trait
monogenic dominant
31
indicate two concequences of FH
atherosclerosis, coronary infarcts
32
how do statins work
. Inhibits HMG co A reductase hence inhibiting cholestrol synthesis
33
name two statins
Lipitor, Crestor
34
what are resins/sequestrants?
Resins bind/sequester bile acid-cholesterol complexes preventing their reabsorbtion by the intestine. increases hdl and decreases LDL.
35
name a resin
Cholestyramine ( brand Questran, prevalite)