Lecture 6: Lipids, Metabolism, Disorders and Analysis Flashcards

1
Q

What are lipid fractions?

A
  • Cholesterol
  • Fatty acids
  • Triglycerides
  • Phospholipids
  • Other lipid soluble substances (fat-soluble vitamins and steroid hormones, etc. (much smaller amount)
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2
Q

What is cholesterol?

A

A vital lipid in the body used for making cell membranes, tissues, steroid hormones, bile acid, vitamin D. Can be made exogenously or endogenously.

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3
Q

Where and how is cholesterol made?

A

Made in the liver from acetyl-CoA.
The reaction HMG-CoA synthase (3-hydroxy-3-methylglutaryl-CoA synthase) produces HMG-CoA from acetyl-CoA, before HMG-CoA is converted into mevalonic acid by HMG-CoA reductase, which goes on to become cholesterol.

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4
Q

How is cholesterol transported?

A

Transported as lipoproteins:
-LDL
-HDL
-IDL

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5
Q

What function does cholesterol play in membranes?

A

It is present in cell membranes to maintain the fluidity, compressibility, water penetration, and intrinsic curvature.

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6
Q

What are triglycerides?

A

Fats in the body that are stored forms of fatty acids, present in many cells in the body but especially in adipose. Held together by a glycerol molecule with 3 ester bonds holding 3 fatty acid chains.

Triglycerides that contain both saturated and unsaturated fatty acids are vital for cell membranes.

Triglycerides are transported as lipoproteins (VLDL and chylomicrons).

Free fatty acids are transported in plasma bound to albumin.

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7
Q

What are fatty acids?

A

Long carbohydrate chains with a carboxylic acid group on one end.
Can have C=C bonds in the chain (unsaturated), or only C-C bonds (saturated). Can be short, medium, or long chain.

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8
Q

Where are certain types of fatty acids obtained from in the diet?

A

Saturated - Animal sources
Unsaturated - Plant sources

An exception is omega-3 fatty acids from fish

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9
Q

What are phospholipids?

A

Similar to triglycerides, with a glycerol molecules bonded to 2 fatty acid chains with the final bond being to a phosphate group bonded to a choline molecule.

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10
Q

What are lipoproteins?

A

Lipids are not soluble, and therefore must be transported by something in plasma. Free fatty acids bind to albumin. And other lipids circulate as lipoproteins.

The structure consists of a single phospholipid layer (with some cholesterol) emulsifying a collection of triglycerides and cholesterol esters, Apolipoproteins are present in phospholipid layer. This creates a polar shell and non-polar core.

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11
Q

What types of lipoproteins are there?

A

Chylomicrons
VLDL -Very low density lipoprotein
IDL -Intermediate density lipoprotein
LDL -Low density lipoproteins
HDL -High density lipoproteins

From order of least dense to most.

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12
Q

What are chylomicrons?

A
  • The largest and most buoyant lipoprotein.
  • Formed in the intestine and are a transport vehicle for dietary fat.
  • Triglyceride rich
  • Exogenous pathway
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13
Q

What are VLDLs?

A
  • Second largest lipoprotein
  • Largest lipoprotein that contains endogenous lipid
  • Triglycerides are endogenous
  • Triglyceride rich
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14
Q

What are IDLs?

A
  • Intermediate composition of lipids
  • Carries endogenous lipids
  • Produced as an intermediate between VLDL and LDL
  • Core contains cholesterol ester and triglycerides.
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15
Q

What are LDLs?

A
  • The main cholesterol containing lipoprotein
  • End product of VLDL catabolism
  • Mostly cholesterol esters in core
  • Has apolipoprotein B100 embedded in phospholipid monolayer, as well as embedding itself in the core.
  • “bad cholesterol”
  • Endogenous pathway
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16
Q

What are HDLs?

A
  • Smallest and densest lipoprotein
  • Crucial component of endogenous and exogenous pathways
  • “good cholesterol”
  • Cholesterol rich
17
Q

What are apolipoproteins?

A

An important part of structure and metabolism of lipoproteins
- Four classes: A, B, C, and E (former D was placed in class A
- Serves as a ligand for receptors and an enzyme cofactor

18
Q

What apolipoproteins are present on which lipoproteins?

A

A1 and A2 - Chylomicrons, HDL

B48 - Chylomicrons. VLDL

B100 - IDL, VLDL, LDL

C2 - Chylomicrons, HDL, VLDL, IDL

C3 - Chylomicrons, HDL, VLDL, IDL

E - C3 - Chylomicrons, HDL, VLDL, IDL

19
Q

What does each apolipoprotein do?

A

A1 and A2 - LCAT activator

B48 - Secretion of chylomicrons/VLDL

B100 - LDL receptor binding

C2 - Lipoprotein lipase activator

C3 - Lipoprotein lipase inhibitor

E - IDL and remnant particle receptor binding

20
Q

What is lipoprotein (a)?

A
  • Strong risk factor for CVD
  • Pro-inflammatory, pro-atherotic, pro-thrombotic
  • LDL-like particle containing apoB bound to apo(a)
  • Not lowered by statins / ezetimibe / fibrates
  • Plasma conc. is genetically determined, and short apo(a) means high conc. in blood
  • Some new drugs can target it
21
Q

What is lipoprotein X?

A

Found only in plasma of subject in cholestasis or have familial LCAT deficiency (cholesterol esterification enzyme).

Major protein is albumin, with Apo C and D also.

Contains no ApoB, not recognised by LDL-Receptor

Can slow down the process of atherosclerosis by inhibition of LDL oxidation.

22
Q

What is lipoprotein lipase?

A

Attached to luminal surface of endothelial capillaries.
Predominant on adipose and muscle cells.
Catalyses triglycerides into constituents

23
Q

What is LCAT?

A

Enzyme for cholesterol -> cholesterol ester

24
Q

What is CEPT?

A

Protein that transfers cholesterol esters from HDL to VLDL

25
Q

What is ACB1?

A

Adenosine triphosphate-binding cassette protein, controls the efflux of free cholesterol from cells.

26
Q

How do chylomicrons enter bloodstream?

A

From intestines to lymphatic ducts and then on to bloodstream through thoracic lymph duct.

27
Q

Why do chylomicrons have ApoCII?

A

Because apoCII is an activator or lipoprotein lipase, allowing cells to use contents.

28
Q

What happens as chylomicrons circulate?

A

Triglycerides are used up and cholesterol ester is uptaken

29
Q

Where is VLDL formed?

A

Hepatocytes

30
Q

How does VLDL become IDL?

A

Triglycerides are removed from VLDL by IDL.

31
Q

How does IDL become LDL?

A

IDL goes to the liver and triglycerides are broken down by hepatic lipase to make it more dense.

32
Q

What can happen to LDLs after they have been produced?

A

Can circulate to peripheral tissues where they are uptaken by LDL-R and can be broken down in lysosomes to unesterified cholesterol and amino acids.

33
Q

What is reverse cholesterol transport?

A

The function HDLs play in which they distribute apolipoproteins to VLDLs and CMs in exchange for triglycerides. And the collection of free cholesterol from peripheral cell membranes, where it is converted to cholesterol esters. Receives cholesterol from cells via ACB1

34
Q

What 3 forms of HDL are there?

A

Nascent - very low cholesterol content, just phospholipids and apolipoproteins.

HDL3 - More cholesterol collected, gets more full

HDL2 - Lots of cholesterol, full

35
Q

What are oxidised LDLs?
How do they contribute to atherosclerosis?

A

Oxidised forms of LDLs that are produced when LDLs infiltrate endothelium, phagocytosed by monocyte derived macrophages to produced foam cells, this spurs the infiltration and proliferation of smooth muscle cells inside the intima between endothelium and smooth muscle tissue through basement membrane. This combination of smooth muscle cells and foam cells produces plaque that build up and results in atherosclerosis.

36
Q

Describe the contents of the plaque in atherosclerosis.

A
  • Foam cells
  • Dead foam cells
  • Collagen
  • Lipids
  • Pro-inflammatory cytokines
  • DNA
37
Q

How can atherosclerosis cause death?

A

When plaque build-up ruptures, it causes a reaction. Due to clotting factors and platelets flocking to the site of rupture, clots can forms and impede blood flow, resulting in acute myocardial infarction, or an embolism can move to the lung (pulmonary embolism), or brain (stroke).