Cholestero, Lipoprotein Metabolism And Steroids Flashcards Preview

Biochem BLOCK 2 > Cholestero, Lipoprotein Metabolism And Steroids > Flashcards

Flashcards in Cholestero, Lipoprotein Metabolism And Steroids Deck (61):
1

Steroids

-organic compound with the four fused rings arranged in a specific configuration (ABCD ring system)

2

What is the ring arrangement of the steroids?

ABCD

3

Sterols

A subgroup of steroids with a hydroxyl group at a the 3-position of the A ring
Steroid + OH

4

Cholesterol

-highly hydrophobic compound
-the major sterol in animal tissues

Sterol + hydrocarbon tail

5

Steroid nucleus

The 4 ring structure shared by all steroids

6

What is an essential structural component of all animal cell membranes ( ~30%)?

Cholesterol

7

Cholesterol function

-essential membrane structural component
-required to maintain both membrane structural integrity and fluidity at different temps (flexibility)
-enables animal cells to dispense with the cell shape in order to protect membrane integrity and cell viability
-components of lipid rafts

8

Cholesterol is a precursor for the synthesis of

-bile salts
-steroid hormones
-vitamin D

9

What types of cholesterol are there?

Esterified and unesterified

10

Unesterified cholesterol

-free cholesterol
-what we normally refer to
-found in the membranes of all animal cell membranes

11

Esterified cholesterol

-cholesteryl esters
-form in which it is put in lipoprotein particles that go into plasma
-not found in the membranes
-most of the plasma cholesterol is in this form

12

What cells can synthesize cholesterol?

Almost all of the

13

What is the central organ for synthesis, distribution, and elimination of cholesterol?

Liver

14

What organs contribute most significantly to the overall cholesterol pool?

-liver
-intestine
-steroidogenic tissues

15

Sources of liver cholesterol

1. Diet (delivered from chylomicron remnants)
2. Delivered via HDLs (reverse cholesterol transport)
3. De Novo synthesis

16

Routes for cholesterol clearance from the liver

-secretion into VLDL/LDL
-secretion of free cholesterol into the bile
-conversion to bile salts

17

What is the major route of elimination of cholesterol in the body?

Conversion to bile salts

18

Cholesterol balance

-No precise
-leads to gradual deposition of cholesterol in the tissues, especially the endothelial linings of blood vessels

19

Lipid depositions over time

-very slow process
-lead to plaque formation, causing narrowing of the blood vessels (atherosclerosis) and increased risk of cardio-, cerebro-, and peripheral vascular disease INCLUDING BLOCKING BLOOD SUPPLY TO THE EYE
-can be life threatening

20

Atherosclerosis

Narrowing of the blood vessels

21

Substrates for cholesterol synthesis

-acetyl CoA (builds carbon skeleton)
-reducing equivalents NADPH
-ATP is needed (produce energy)

*all need to be present together

22

When does cholesterol synthesis occur?

-in well fed state (when all substrates are available)
-when the cholesterol supply is low (VERY tightly regulated)

23

Cholesterol synthesis is...

-composed of multiple steps
-divided into 6 stages

24

Where does synthesis of cholesterol happen?

Hepatocytes

25

Stage 1 of cholesterol synthesis

Conversion of acetylene CoA to HMG CoA
-enzyme: HMG-CoA synthase

26

HMG CoA synthase

-Convert acetylene CoA to HMG CoA
-2 isozymes in liver
-cytosolic of cholesterol synthesis
-mitochondrial for ketone bodies

27

What isozyme of HMG CoA synthase do we want for cholesterol synthesis?

Cytosolic

28

Stage 2 of cholesterol synthesis

Synthesis of mevalonate
-enzyme:HMG CoA reductive
-rate limiting key regulatory step
-irreversible
-integral membrane proline of ER facing the cytosolic
-inhibited by statin drugs (competitive inhibitor, lower LDL particles)

29

HMG-CoA reductive

Synthesis of mevalonate

30

Mevalonate

-synthesized in step 2 with HMG-CoA reductase
-integral membrane protein of ER facing the cytosol
-inhibited by statin drugs

31

What way does mevalonate face?

The cytosolic side of the rough ER

32

What is the rate limiting key regulatory step in cholesterol synthesis?

Synthesis of mevalonate from HMG-CoA reductase

33

What are the other 4 not so important steps of cholesterol synthesis?

3. Conversion of mevalonate to isoprenyl pyrophosphates with loss of CO2
4. Conversions of isoprenyl pyrophosphates to squalene
5. Conversion of squalene to lanosterol
6. Conversion of lanosterol to cholesterol

34

How many molecules of mevalonate are required to make one molecule of cholesterol?

6

-since each molecule of mevalonate requires 3 acetyl CoA, ultimately 18 molecules of acetyl CoA are required to make one molecule of cholesterol

35

How many molecules of acetylene Coa are required to make 1 molecule of cholesterol?

18

36

Are the steps in cholesterol reversible or irreversible?

Many of the steps are irreversible, and humans DO NOT have the enzymes to perform the reverse reactions

37

Can cholesterol be metabolized to CO2 like sugars and fats

No

38

Are the intermediates charged or neutral in cholesterol synthesis?

Neutral
-since the synthesis takes place in the cytoplasm, many of the intermediates are charged to make them soluble, until the formation of squalene (at this point the molecule is associated with carrier proteins)

39

What does any hydrophobic molecule need?

A protein carrier

40

Regulation of cholesterol synthesis via HMG CoA reductase

1. Sterol-dependent regulation of the levels of the enzyme protein product
2. Sterol-independent covalent modifications-phosphorylation/dephosphoryaltion
3. Hormonal regulation

41

Sterol dependent regulation of the levels of the enzyme protein product

-enzyme gene transcription and expression (via SREBP transcription factor)
-enzyme degradation (via ubiquitination)

42

Sterol-independent covalent modifications-phosphorylation/dephosphorylation

Via AMPK reflecting the energy state of the cell

43

Hormonal regulation of cholesterol synthesis via HMG CoA reductase

-insulin and thyroxine upregulate HMG CoA reductase expression-glucagon and glucocorticoids downregulate it. (Stress/starvation)

44

Degradation of cholesterol

Ring structure CANNOT be metabolized to CO2 and H2O in humans

45

The intact sterol nucleus is eliminated by:

-Conversion to bile acids and bile salts
-Secretion of cholesterol into the bile
- Some of the cholesterol in the intestine is modified by bacteria before excretion

46

Bile

A watery mixture of ORGANIC and INORGANIC compounds by the liver to facilitate the digestion of lipids in the small intestine.
-Continuously produced and stored in the gallbladder

47

Bile salts

The major constituent of bile produced in liver cells from bile acids. 61%

48

Bile acids

Precursor for the synthesis of bile salts, produced in liver cells from cholesterol.

49

Formation of bile salts

Cholesterol > Bile acids > Bile salts

50

Bile salt circulation

Reabsorbed from the intestine and sent back to the liver to be used again (highly efficient)

51

What is the only significant loss of the steroid nucleus

Very small loss (>5%) as free cholesterol in the feces from the body under normal circumstances

52

Cholelithiasis

-gall stones
-form in the gall bladder where bile is stored

53

Origin of gall stones

-derived from cholesterol and result from too little bile salts and/or too much cholesterol in the gall bladder (the bile salts are required to solubilize free cholesterol)

54

Possible causes of gall stones

-inefficient enterohepatic cycling (bile salts not reabsorbed due to Ileal disease
-liver dysfunction (bile acid deficiency)
-other idiopathic reason

55

Lipoproteins

Spherical macro molecular complexes of lipids and specific proteins (apolipoproteins)

56

Function of lipoproteins

-to transport cholesterol, fats, and fat-soluble compounds to the plasma
-major transport system of lipid soluble vitamins

57

Types of lipoproteins

-chylomicrons
-VLDL
-LDL
-HDL

58

Chylomicron

-lipoprotein that transports dietary lipids, produced in enterocytes

59

VLDL

-lipoprotein that transports newly synthesized lipids produced in hepatocytes

60

LDL

Lipoprotein that transports cholesterol to the peripheral tissues

61

HDL

Lipoprotein that transports cholesterol from the periphery to the liver
-route if eliminating excess cholesterol