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Chemical Pathology > Lipoproteins And Cholesterol Metabolism > Flashcards

Lipoproteins And Cholesterol Metabolism Flashcards

1
Q

List the three major plasma lipids

A

TGs
Cholesterol
Lipoproteins

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2
Q

What are the types of lipoproteins

A

Chylomicrons
HDL
LDL
IDL

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3
Q

What are the steps of cholesterol biosynthesis

A

Acetyl CoA + acetoacetyl CoA -> HMG-CoA -> mevalonate -> IPP -> GPP -> FPP -> Squalene -> Lanosterol -> Cholesterol -> bile salts (liver) or steroids (endocrine glands)

Enzymes
(2) HMG-CoA reductase

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4
Q

What are the steps in the biosynthesis of bile salts

A

Cholesterol -> 7-hydroxycholesterol -> cholyl CoA or chenodeoxycholyl CoA

Enzymes
(1) 7-hydroxylase

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5
Q

What are the clinical significance of bile acid synthesis

A

Their synthesis and subsequent excretion in the feces represent the only significant mechanism for the elimination of excess cholesterol
Bile acids and phospholipids solubilize cholesterol in the bile, thereby preventing the precipitation of cholesterol in the gall bladder
They facilitate the digestion of dietary triacylglycerols by acting as emulsifying agents that render fats accessible to pancreatic lipases
They facilitate the intestinal absorption of fat-soluble vitamins

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6
Q

What are free fatty acids bound to in the blood

A

Albumin
Others are transported in the blood as part of lipoproteins

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7
Q

Describe the structure of lipoproteins

A

A core consisting of a droplet of triacylglycerols and/or cholesteryl esters and
A surface monolayer of phospholipid, unesterified cholesterol and specific proteins (apolipoproteins, e.g., apoprotein B-100 in low density lipoprotein).

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8
Q

Lipoproteins are classified based on

A

Their density

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9
Q

Which lipoprotein is the largest, lowest in density due to high lipid/protein ratio and the highest in triacylglycerols as % of weight

A

Chylomicrons

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10
Q

Which lipoproteins is the highest in cholesteryl esters as % of weight

A

LDL

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11
Q

Which lipoprotein is the 2nd highest in triacylglycerols as % of weight

A

VLDL

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12
Q

What is lipoprotein (a)

A

Lipoprotein (a) [Lp(a)] (also known as apo(a), not to be confused with apoA), represents a class of lipoprotein particles defined by the presence of apolipoprotein(a), a unique glycoprotein linked by a disulfide bond to apolipoprotein B-100 to form a single macromolecule and has been associated with premature cardiovascular disease

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13
Q

How many different apoprotein types has VLDL

A

5 different apoprotein types

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14
Q

List the five apoprotein types of VLDL

A

B-100, C-I, C-II, C-III, & E

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15
Q

Which apoprotein is associated with the surface monolayer of LDL.

A

Apoprotein B-100

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16
Q

What is the known function for apo B

A

Secretions of chylomicrons

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17
Q

What is the known function of Apo E

A

Binding of IDL and remnants to particles to receptor

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18
Q

What is the known function for Apo C

A

Binding of LDL to receptor

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19
Q

What is the known function for Apo A

A

Cofactor for LCAT

20
Q

What are some functions of apoproteins

A
  1. Make lipoprotein soluble
  2. Serve as receptors for cell surface receptors recognition and binding.
  3. Activation of lipase enzymes
  4. Diagnosis of CVD and Alzheimer disease
21
Q

What is the clinical significance of plasma cholesterol concentration

A

Atherosclerosis

22
Q

What are some ways HDL decreases atherogenicity

A
  1. Removal of atherogenic plaques in blood vessels
  2. Decrease endothelia inflammation
  3. Decrease oxidative stress of endothelial cells
  4. Increase NO2 production in endothelial cells
23
Q

HDL decrease atherogenicity by a process called

A

Reverse cholesterol transport

Mature HDL can acquire additional cholesterol from cells via ABCG1, SR- B1 or passive diffusion. The HDL then transports the cholesterol to the liver directly by interacting with SR-B1 or indirectly by transferring the cholesterol to VLDL or LDL a process facilitated by CETP

24
Q

Mention some cholesterol disorders

A

Hypercholesterolemia
Nephrotic syndrome
Hypocholesterolemia
Lipidoses

25
Q

What drug is used to manage hypercholesterolemia and what is its MOA

A

Cholestyramine

Combines with bile acids and prevent reabsorption, therefore excrete cholesterol, sitosterol ppt int. chol and prevent absorption. Large doses of niacin

26
Q

Low LDL, results in retinitis, pigmentosa, CNS
What condition is this

A

Acanthocytosis

27
Q

Low HDL results in yellow gray tonsils
What condition is this

A

Tangier’s disease

28
Q

Mention some conditions which cause hypocholesterolemia

A

Hepatitis
Anaemia
Cachexia
Severe hyperthyroidism

29
Q

What are the classifications for hypercholesterolemia

A

Type I Hyperchylomicronaemia/ Hyperlipoproteinaemia
•Type II Hyper β-lipoproteinaemia (Sf 0-12)
•Type III increase in β-lipoproteinaemia (Sf 12-100) hypercholestrolaemia
•Type IV Hyper pre β-lipoproteinaemia
•TypeV Hyperpreβ-lipoproteinaemia and chylomicronaemia

Oxidized low-density lipoprotein (ox-LDL) causes endothelial dysfunction in part by decreasing the availability of endothelial nitric oxide (NO)

30
Q

What are the various treatments for hypercholesterolemia

A
  1. HMG CoA reductase inhibitors simvastatin and lovastatin, inhibits the committed step in cholesterol biosynthesis and lowers plasma total cholesterol
  2. Proteins Convertase substilisin/kexin 9 (PCSK9), low PCSK9 activity recycle LDL-C receptors to the hepatocytes to clear up plasma LDL-C
  3. Upregulates eNOS expression
31
Q

What is lipidosis

A

Lipidoses are genetic diseases due to disease-specific defects in the enzymatic catabolism of lipids, with accumulation of the respective lipid substrate in the nervous system and/or peripheral tissues

32
Q

How is the chemical diagnosis of lipidoses accomplished

A

The clinical chemical diagnosis of lipidoses can be accomplished by demonstration of the enzyme defect and/or substrate accumulation in body fluids (urine, blood serum), leukocytes, cultured fibroblasts, amniotic fluid cells, or amniotic fluid, respectively

33
Q

What are the various kinds of lipidoses

A

GM1 gangliosides - B - galactosidase
GM2 Tay Sachs - Hexosamindase A
Sandhoff disease - Hexosamindase A+B
Gaucher’s disease - Acidic - B - Glucosidase
Metachromatic Leukodystrophy - Arylsulfatase A Neuronal
ceroid lipofuscinosis

34
Q

What is Refsum’s disease

A

Refsum disease is an autosomal recessive neurological disease that results in the over-accumulation of phytanic acid in cells and tissues

35
Q

What is the formula for calculating estimated body fat according to Lean et al., (1996)

A

Women (%body fat) = [(0.438 * WC in cm) + (0.221 * age in years)] – (9.4).

Men (%body fat) = [(0.567 * WC in cm) + (0.101 * age in years)] – (31.8)

36
Q

What is the formula for coronary risk

A

C.RISK = [T.CHOL] / [HDL]

37
Q

What is the formula for calculating Atherogenic index of the plasma (AIP).

A

AIP = Log [Triglyceride/ HDL]

38
Q

The GM1 gangliosidoses (monosialoteterahexosylganglioside) are caused by a deficiency of ………… (what enzyme), with resulting abnormal storage of acidic lipid materials in cells of the central and peripheral nervous systems, but particularly in the nerve cells

A

Beta-galactosidase

39
Q

The GM2 gangliosidoses are a group of three related genetic disorders that result from a deficiency of the enzyme ……….. (what enzyme). This enzyme catalyzes the biodegradation of fatty acid derivatives known as gangliosides.The diseases are better known by their individual names

A

Beta-hexosaminidase

40
Q

What are LSDs

A

Lysosomal storage diseases (LSDs) are a group of about 50 rare inherited metabolic disorders that result from defects in lysosomal function

41
Q

How do LSDs come about

A

Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other parts of the cell for recycling
This process requires several critical enzymes. If one of these enzymes is defective, because of a mutation, the large molecules accumulate within the cell, eventually killing it

42
Q

What are some symptoms of LSD

A

•Delay in intellectual and physical development
•Seizures
•Facial and other bone deformities.
•Joint stiffness and pain
•Difficulty breathing
•Problems with vision and hearing.
•Anemia, nosebleeds, and easy bleeding or bruising
•Swollen abdomen due to enlarged spleen or liver

43
Q

What is Tay-Sach disease

A

This disorder is categorized as a lysosomal storage disease. Lysosomes are the major digestive units in cells. Enzymes within lysosomes break down or “digest” nutrients, including certain complex carbohydrates and fats. Tay-Sachs disease is inherited as an autosomal recessive trait

44
Q

What is nephrotic syndrome

A

1.The mechanism by which this occurs is unclear, the main cause is probably due to increase in hepatic lipogenesis probably a response to hypoalbuminemia
2.but elevations in the plasma concentration of cholesteryl ester transfer protein in nephrotic patients may contribute by shuttling cholesteryl esters from HDL2 to very low-density lipoproteins (VLDL)
3.Hypercholesterolaemia may cause glomerosclerosis a complication of N.S
3. DM (Increased lipolysis)
4. Cholistasis

45
Q

How do hepatocytes synthesize VLDLs

A

Uses the availability of trig. Synthesizes in the ER lumen in response to FAA influx
•An increased delivery of FA increases secretion of VLDL-trig through apo B-100
•Small amounts are produced by the enterocytes in the fasting state

Chemical Pathology (16 decks)

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