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BIOCHEMISTRY > ME04 - Cholesterol Synthesis, Transport and Export > Flashcards

ME04 - Cholesterol Synthesis, Transport and Export Flashcards

1
Q

What are the Biologic Importance of Cholesterol?

A

Structural component of all cell membranes

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2
Q

Cholesterol Synthesis and Transport

A

Liver (Biliary CHOL 2g/d)&raquo_space; Stomach (Dietary CHOL 0.4g/d)&raquo_space; Duodenum&raquo_space; Jejunum&raquo_space; Ileum (ABSORPTION 50%)&raquo_space; Colon (Fecal excretion 1.2 g/d)

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3
Q

When CHOL is transported through a channel and pumped back out by a complex. Ezetimibe acts which part?

A

Ezetimibe acts on NPC1L3

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4
Q

CHOLESTEROL STRUCTURE

A

Highly hydrophobic

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5
Q

Steroids with 8 to 10 carbon atoms in the side chain at C17 and a hydroxyl group at C3

A

Sterols

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6
Q

Major sterol in animal tissues

A

Cholesterol

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7
Q

Cholesterol with a fatty acid attached at C3 and esterified

A

Cholesteryl Esters (CE) | Not normally found in membranes

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8
Q

Why are Cholesteryl Esters esterified?

A

This makes the structure even more hydrophobic than free cholesterol

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9
Q

Fate of Cholesteryl Esters

A

Must be transported in association with a protein (lipoprotein), or be solubilized by phospholipids and bile salts in bile

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10
Q

SYNTHESIS OF CHOLESTEROL

A

Cholesterol is synthesized by virtually all tissues, but is largely contributed by the liver, intestine, adrenal cortex, and reproductive tissues

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11
Q

8 Steps of Cholesterol Synthesis

A
  1. Mevalonate/Mevalonic Acid (6C) is converted to Mevalonate 5 phosphate in 2 steps requiring ATP
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12
Q

SYNTHESIS OF 3-HYDROXY-3- METHYGLUTARYL CoA (HMG CoA)

A

Similar to the pathway that produces ketone bodies

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13
Q

Rate-limiting step in cholesterol synthesis

A

HMG-CoA&raquo_space; (HMG-CoA Reductase)&raquo_space; Mevalonate

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14
Q

An intrinsic membrane protein of the ER with the catalytic domain projecting into the cytosol

A

HMG CoA reductase

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15
Q

What inhibits in the rate-limiting step of Cholesterol Synthesis

A

This step is inhibited by statins (Simvastatin, Atorvasatin, etc.)

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16
Q

What catalyzes many of the reactions involved in converting lanosterol to cholesterol and other steroids

A

cytochrome P450 enzyme superfamily

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17
Q

An intermediate on the pathway for cholesterol synthesis,

A

Farnesyl pyrophosphate

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18
Q

FARNESYL PYROPHOSPHATE/DIPHOSPHATE GIVES RISE TO:

A

DOLICHOL for the synthesis of N-glycosides

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19
Q

What is the major control point in the REGULATION OF CHOLESTEROL SYNTHESIS

A

The reaction catalyzed by HMG CoA reductase, which is inhibited by mevalonate, cholesterol, and statin drugs

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20
Q

What is only inhibited by dietary cholesterol

A

Hepatic synthesis

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21
Q

What increases HMG CoA reductase activity?

A

Insulin or thyroid hormone

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22
Q

What decreases HMG CoA reductase activity?

A

Glucagon or Glucocorticoids

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23
Q

CELL CHOLESTEROL INCREASE IS DUE TO:

A

Uptake of cholesterol-containing lipoproteins by receptors

24
Q

CELL CHOLESTEROL DECREASE IS DUE TO:

A

Efflux of cholesterol from the cell membrane to HDL promoted by LCAT (lecithin:cholesterol acyltransferase). LCAT is also known as PCAT

25
Q

WHAT IS THE ROLE OF CHOLESTERYL ESTER TRANSFER PROTEIN (CETP) IN PLASMA LIPID TRANSPORT

A

CETP facilitates the transfer of CE from HDL to VLDL, IDL, and LDL in exchange for TAG.

26
Q

What is VLDL and function of VLDL

A

VLDL is produced from the liver and is composed mostly of TAG

27
Q

What is LDL and function of LDL

A

LDL contains less TAG than VLDL

28
Q

The ring structure of cholesterol cannot be metabolized to carbon dioxide and water in humans. True or False?

29
Q

How is the intact sterol nucleus eliminated?

A

The intact sterol nucleus is eliminated by conversion to bile acids and bile salts

30
Q

Predominant mechanisms for the excretion of excess cholesterol

A

Synthesis of bile acids

31
Q

The excretion of cholesterol in the form of bile acids is insufficient to compensate for an excess dietary intake of cholesterol. True or False?

32
Q

Some of the cholesterol in the intestine is modified by bacteria before excretion. What do you call the primary compound made ?

A

Coprostanol

33
Q

Consists of a watery mixture of organic and inorganic compounds

34
Q

Quantitatively the most important organic components of bile

A

Lecithin and bile salts (conjugated bile acids)

35
Q

Fate of Bile

A

Can pass directly from the liver where it is synthesized to the duodenum through the common bile duct, or be stored in the gallbladder

36
Q

STRUCTURE OF BILE ACIDS

A

Contains 24 carbons with 2 or 3 hydroxyl groups and a side chain that terminates in a carboxyl group

37
Q

The rate limiting step in bile acid synthesis

A

The reaction catalyzed by the 7_-hydroxylase

38
Q

What is responsible for the down-regulation and up regulation of the limiting step?

A

Down-regulated by cholic acid

39
Q

SYNTHESIS OF BILE SALTS

A

Before the bile acids leave the liver, they are conjugated to a molecule of either glycine or taurine by an amide bond between the carboxyl group of the bile acid and the amino group of the added compound

40
Q

Where does Conjugation of bile salts takes place

A

Peroxisomes

41
Q

The ratio of glycine to taurine forms in the bile

42
Q

The salt forms of bile salts are fully ionized (negatively charged) at physiologic pH. True or False?

43
Q

Rationale behind why bile salts are more effective solubilizers

A

Because of their enhanced amphipathic nature

44
Q

What is the ACTION OF INTESTINAL FLORA ON BILE SALTS

A

Bacteria in the intestine can remove glycine and taurine and regenerate bile acids

45
Q

What are the precursor or Deoxycholic Acid and Lithocholic Acid

A

DEOXYCHOLIC ACID FROM GLYCOCHOLIC ACID

46
Q

Fate of Bile Salts

A

Of the 15 to 30 grams of bile salts secreted from the liver, more than 95% are reabsorbed through the ileum, pass through the portal vein, and are reused

47
Q

What are Bile acid sequestrants and their function

A

Bile acid sequestrants like cholestyramine bind bile acids in the gut and prevent their reabsorption, promoting cholesterol excretion

48
Q

Due to the deposition of cholesterol and cholesteryl ester from the plasma lipoproteins to the artery walls

A

Atherosclerosis

49
Q

What protects a person from Atherosclerosis?

A

A high HDL and low LDL protects a person from this complication. This is one of the benefits provided by exercise

50
Q

What are the events leading to Atherosclerosis?

A

Endothelial Dysfunction&raquo_space; Inflammation&raquo_space; Oxidation&raquo_space; Plaque instability and thrombus

51
Q

Event when an embolus blocks the coronary arteries

A

Myocardial Infarction

52
Q

Due to various defects in lipoprotein formation, transport, or destruction

A

DYSLIPOPROTEINEMIAS

53
Q

What are some of the diseases that exhibit abnormal lipoprotein patterns that resemble dyslipoproteinemias

A

Diabetes Mellitus, Hypothyroidism, Kidney disease, and atherosclerosis

54
Q

Occurs when more cholesterol enters the bile than can be solubilized by the bile salts and lecithin present

A

CHOLELITHIASIS (GALLSTONES)

55
Q

What is the treatment of choice for Cholelithiasis?

A

Surgery is the treatment of choice, but administration of chenodeoxycholic acid may help to supplement the bodys supply of bile acids

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