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Lipid Metabolism Flashcards

1
Q

Cardiovascular Disease risk factors (5)

A

Obesity
Smoking
Type 2 diabetes
Genetic risk factors - family history of vascular disease
Hyperlipidaemias - in particular relating to cholesterol

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2
Q

Lipids and _____________ are central to energy metabolism and closely associated with coronary heart disease.

A

Lipoproteins

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3
Q

Chylomicrons

A

Transport triglycerides throughout the body. Large core with TG and Chol-Ester.

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4
Q

VLDL

A

Very low density lipoprotein. Carry TG from liver to periphery.

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5
Q

LDL

A

Low density lipoproteins. Carry cholesterol to periphery.

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6
Q

HDL

A

High density lipoproteins. Carry excess cholesterol from periphery to liver. Anti-atherogenic. “Good”

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7
Q

Apolipoproteins

A

located on the surface of lipoprotein particles. Provides structure and act as ligands for receptors - targeting.
Important for diagnostic tests.
Accurate measurement of lipid is important for diagnosis and treatment of patients.

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8
Q

ApoA1

A

Major protein in HDL
Used to measure the amount of anti-atherogenic HDL in plasma

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9
Q

ApoB

A

Major protein on LDL and VLDL, chylomicrons
Ligand for LDL receptor
High levels = heart disease
Better overall marker of risk than LDL alone and better risk marker of vascular disease
Used as a guide to the adequacy of statin treatment , better than any cholesterol index

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10
Q

ApoE

A

Majorprotein on LDL, VLDL, HDL
Ligand for LDL receptor

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11
Q

What are the three isoforms of ApoE?

A

Apo E2, E3, E4

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12
Q

Components of a lipoprotein

A

Triglyceride
Phospholipid
Cholesterol
Cholesterol ester
Apolipoprotein

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13
Q

Building block for triglycerides and phospholipids

A

Fatty acid

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14
Q

Triglyceride structure

A

3 fatty acids connected to a glycerol with ether bonds
Important for storage and transport of energy in the body
No charged groups => very hydrophobic
May contain both saturated and unsaturated fatty acid

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15
Q

Phospholipids

A

2 fatty acids, glycerol and a phosphogroup (neg)

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16
Q

Cholesterol

A

Unsaturated steroid alcohol
Can form an ester bond with a fatty acid generating a cholesterol ester
Essential part of cell membranes and for formation of hormones and bile salt

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17
Q

Functions of fatty acids

A

Building blocks of triglycerides and phospholipids
Source of metabolic energy

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18
Q

Function of triglycerides

A

Part of the cell membrane
Storage of energy (adipose tissue)

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19
Q

Where are triglycerides synthesised?

A

Liver

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20
Q

Where are triglycerides metabolised?

A

Intestine

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21
Q

How are dietary TGs transported?

A

In chylomicrons

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22
Q

High levels of ___________ are related to a higher risk of heart and blood vessel disease independent of high cholesterol.

A

TGs

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23
Q

What decreases levels of TGs? (3)

A

Beta-lipoproteinemia
Malnutrition
Drug use

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24
Q

Phospholipid structure

A

Glycerol backbone and 2 fatty acid chains
Amphipathic

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25
Function of phospholipid
Important component of the cell
26
Cholesterol function
Important structure to cell membranes Starting material for synthesis of steroid hormones (testosterone) and vitamin D Formation of bile salts in the liver -> excretion Plaque formation in blood vessels Cannot be catabolised in most cells Mainly synthesised in liver Excess cholesterol can lead to cardiovascular disease
27
What is the rate limiting step of cholesterol synthesis?
HMG CoA reductase
28
Explain the action of statins on cholesterol synthesis
Statins inhibit HMG Co reductase action -> lowering cholesterol levels
29
Why percentage of cholesterol is esterified?
75%
30
What catalyses cholesterol+fatty acid esterification?
Enzyme lecithin:cholesterol acyltransferase (LCAT)
31
What are the two most abundant cholesterol esters?
Cholesterol linoleate Cholesterol oleate
32
What are the four lipid metabolism pathways?
1️⃣ lipid absorption pathway 2️⃣ exogenous pathway 3️⃣ endogenous pathway 4️⃣ reverse cholesterol transport pathway
33
Functions for pathways 1️⃣-3️⃣ of lipid metabolism (3)
Transport lipid from liver (diet) to peripheral cells Energy metabolism TG->FA Forward transport of cholesterol
34
Features of lipid digestion
Small intestine Pancreatic fluid creates a basic pH Bile salts from gall bladder form water-soluable complexes Pancreatic enzymes hydrolyse lipids
35
Features of lipid absorption
Free fatty acids - absorbed across the intestinal epithelia Triglycerides - hydrolysed by lipase, which act on the ester bond Cholesterol - not metabolised in the intestine. Bile salts mediate transport across intestine wall. Liver.
36
Lipid absorption pathway
TG -> monoglycerides, diglycerides Cholesterolesters -> cholesterol Phospholipids-> lysopholipids Chylomicrons are formed from dietary fat
37
Exogenous pathway
Chylomicrons TG-> fatty acids glycerol LPL protein lipase
38
Mutations in LPL or ApoCII
Familial hyperchylomicronaemia
39
Chylomicron lipolysis
LPL enzyme attached to endothelium wall via glycosaminoglycans ApoC II will bind to LPL on the endothelial surface and activate it Active LPL hydrolyse TG to glycerol and fatty acids Chylomicron remnants cleared by liver Chylomicrons cannot be detected in a fasting plasma sample
40
Endogenous pathway
VLDL transports endogenous TG LPLacts on the VLDL to remove TG VLDL remnants releases cholesterol to HDL where it is esterified by cholesteryl ester transferase protein (CETP) This results in VLDL converting to the denser LDL (via IDL) LDL delivers cholesteryl esters to cells Endocytosis mediated by the LDL receptor
41
Receptor mediated internalisation and metabolism of LDL
Internalised LDL is degraded to amino acids and cholesterol which is released into the cytosol The free cholesterol activates 3 regulatory mechanisms
42
What are the three regulatory mechanisms of LDL metabolism?
⬇️ HMG CoA reductase ⬆️ ACAT ⬇️ LDL receptors
43
Deposition of cholesterol on the artery wall by ____,and attraction of macrophages contribute to plaque formation.
LDL
44
Modified LDL is recognised by ___________ receptors.
Scavenger
45
________________________ is downregulated due to high cholesterol concentration.
LDL receptor (LDLR)
46
__________________ is internalised into the cell by alternative receptors and thereby bypass the feedback mechanism.
Oxidised LDL
47
LDL oxidation
Balance between antioxidants and pro-oxidants in the cell and lipoprotein determine how much lipoprotein is. Oxidised and hence atherogenic potency.
48
Antioxidant
A molecule capable of delaying or inhibiting oxidation of a substrate. Vitamin C, E, ubiquinol Q10, flavonoids
49
Modified LDL
Pro-inflammatory => atherothrombotic disease
50
LCAT
Transfers an acyl group (FA residue) from lecithin to cholesterol to cholesterol ester. HDL
51
LPL
Digests TGs into glycerol +free FA Activated by ApoC-II (at TG-positive lipoproteins) in the capillary endothelium
52
Hepatic lipase
Similar function to LPL
53
Reverse cholesterol transport pathway - HDL
To balance the concentration of cholesterol in the periphery HDL removes excess cholesterol CETP increases the rate of transport LCAT catalyses cholesterol esterification -> HDL-mediated removal of excess cholesterol from macrophages in the arterial wall (activated by its cofactor ApoA1)
54
CETP
Reduces circulating cholesterol-HDL levels by transferring cholesterol-esters to LDL particles High CETP => atherosclerosis
55
________ is a risk factor for CVD
Cholesterol
56
Treatment to lower plasma LDL cholesterol
Diets and lifestyle changes HMG-CoA reductase inhibitors (statins) QRISK2 risk calculator
57
Hypercholesterolemia
The lipid abnormality most closely linked to heart disease. Increased LDL cholesterol.
58
Hypertriglyceremia
Caused by genetic abnormality or hormone imbalance. Insulin, glucagon, pituitary hormone, epinephrine.
59
Combined hyperlipoproteinemia
Elevated levels of both cholesterol and TG. Increased risk of heart disease.
60
Total cholesterol test
Directly linked to a risk of heart disease Decreased in cancer, malnutrition and hyperthyroidism Caveat - measures sum of lipoprotein-cholesterol
61
Total plasma cholesterol levels are affected by: (5)
Diet - polyunsaturated fats lower cholesterol Excercise - increases plasma HDL Age - increases with age Sex - lower in women Genetics/environment - north Europeans higher
62
Bad cholesterol
LDL New research shows IDL, VLDL and apolipoproteins as bad cholesterol also 2014
63
Good cholesterol
HDL Total cholesterol level
64
LDL (bad cholesterol) estimated from ______ concentration.
ApoB
65
Lipoprotein A
LP(a) is a LDL attached to a protein called apo(a) Not fully known what it does If high levels=> increased risk of heart attack and stroke Independent risk factor for cardiovascular disease Largely genetically determined Quantification by immunoassay
66
ApoC
Synthesised in the liver Mainly associated with HDL
67
ApoB48
Chylomicrons
68
ApoB100
Major component of LDL,VLDL, which will give a concentration os these two in serum Immunoassay May be a better indicator of atherogenic particles than LDL cholesterol
69
APO A1
Major protein of HDL Low levels => HDL deficiency and increased risk of early cardiovascular disease
70
LDL-associated PLA2 (PLAC)
Measures the level of lipoprotein associated-phospholipase A2, an enzyme associated with inflammation, stroke and heart attack risk. However levels may also be due to non-arterial causes.
71
C reactive protein and cardiovascular disease
Inflammation of the arteries is a risk factor for cardiovascular disease. CRP has been linked to an increased risk of heart disease, heart attack, sudden death, stroke, and peripheral arterial disease. High Sensitivity (also called Ultra-sensitive) C-reactive protein is known as HS-CRP, US-CRP or CRP for short is used for patients with a predisposition for CVD e.g. genetic. In studies involving large numbers of patients CRP seems to be at least as predictive of cardiac risk as cholesterol levels.
72
CRP
Acute phase protein produced by the liver Released after onset of injury or infection that is causing inflammation
73
Apolipoprotein immunoturbidity assay
Antiserum + antigen → antibody-antigen complex (creates turbidity) Samples read against a known standard on an automated autoanalyzer instrument, such as the ILab, CABAS FARA and Beckman Synchron

Biochemistry (19 decks)

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