4 Lipid Transport metabolism and energy storage Flashcards

1
Q

what is lipoprotein lipase ?

A

LPL is the enzyme for removing the core triacylglycerols from lipoprotein particles such as VLDLs & chylomicrons!

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2
Q

How are lipoproteinemia’s clinically diagnosed? (MGD LINK!)

A

by electrophoresis and PCR

due to diff in lipoprotein charge, weight, size and density

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3
Q

Treatment of hyperlipoproteinemia?

A

diet and lifestyle change - low fat saturated diet/ exercise

also statins - inhibit HMG CoA reductase
bile salts - lower plasma cholesterol

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4
Q

How can ROS cause damage?

A

modification of DNA bases - mispairing/mutations

heinz bodies

lipid peroxidation - hydrophobic environment disrupted

protein side chains - cause loss of function

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5
Q

mechanisms of cell defences

A

superoxide dismutase/catalase

glutathione peroxidase- scavenging enzymes, catalyse H2O2 to H2O + O2

antioxidants - Vit A/C/E

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6
Q

what is meant by respiratory burst?

A

immune system (neutrophils) rapidly release ROS/RNS, produced by NADPH oxidase; *myeloperoxidase

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7
Q

What are ROS/RNS?

A

Free radicals have unpaired electrons, will take from other molecules

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8
Q

what is the most reactive and damaging radical?

A

hydroxyl radical (OH●)

formed by electron transport chain - escaped e

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9
Q

LDL function

A

Transport of cholesterol synthesised in liver to body tissues

half life is longest in blood, more susceptible to oxidative damage

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10
Q

chylomicrons function

A

transport dietary triacylglycerols from intestine to adipose tissues

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11
Q

VLDL function

A

transport of triacylglycerols synthesised in liver to adipose tissues

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12
Q

HDL function

A

Transport excess tissue cholesterol to the liver for disposal as bile salts!

ABCA1 protein - transfers cholesterol to HDL

LCAT (lecithin cholesterol acetyltransferase) - converts cholesterol to esters

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13
Q

What are foam cells?

A

oxidised LDL taken up by macrophages transform to foam cells

causes atherosclerotic plaque build up

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14
Q

types of hyperlipoproteinemia?

A

Ia - chylomicrons effected in fasting, defect w/ LPL

IIa - raised LDL, defect in LDL receptor, can cause CAD

IIb - raised LDL&VLDL, unknown cause, can lead to CAD

III - raised LDL, defect w/ apoE,

IV - raised VLDL, unknown cause

V - raised chylomicrons&VLDL, unknown cause

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15
Q

what is glycogenesis?

A

forming glycogen in muscle or liver during fed/rest

bonds residues 1,4 bonds and 1,6 bonds

rate limiting factor - glycogen synthase

glucagon and adrenaline inhibit

insulin enhances

glucagon has no effect in muscle

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16
Q

what is glycogenolysis?

A

breaking down glycogen in muscle or liver during stress or exercise

breaks residue bonds

rate limiting factor - glycogen phosphorylase

glucagon and adrenaline enhance

AMP also enhances

insulin inhibits

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17
Q

glycogen storage disease - Von Grieke

A

excess glycogen storage

G6P deficiency

tissue damage (excess), fasting hypoglycaemia (low blood glucose)

large liver

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18
Q

glycogen storage disease - McArdles disease

A

insufficient glycogen degradation

glycogen phosphorylase deficiency

leads to poor exercise tolerance, muscle pain/cramps

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19
Q

what enzyme maintains the balance b/w glycogen synthesis and breakdown?

A

phosphoglucomutase

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20
Q

gluconeogenesis?

A

forming glucose de novo during fasting more than 8 hours

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21
Q

precursors for gluconeogenesis?

A

pyruvate
lactate
Amino Acids
glycerol
galactose
fructose

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22
Q

2 enzymes essential of gluconeogenesis?

A

PEPCK - step 10

fructose 1,6 bisphosphate - step 3

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23
Q

what is lipogenesis, where does it occur and what enzyme?

A

fatty acid synthesis

occurs in cytoplasm

fatty acid synthase sequential addition of 2 carbons

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24
Q

what does AMP-activate protein kinase (AMPK) do?

A

activated by AMP (low energy signal)

promotes cellular ATP production via activation of catabolic pathways and inhibition of anabolic pathways

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25
Q

Cholesterol is a precursor of which steroid hormones (4)

A

TACO
Testosterone
Aldosterone
Cortisol
Oestrogen

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26
Q

How are heinz bodies formed

A

precipitate haemoglobin

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27
Q

How are phospholipids classified

A

According to polar head group

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28
Q

How can a stroke or myocardial infarcation occur from an atherosclerotic plaque

A

Ruptures
Triggers thromobis and clotting cascade

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29
Q

How do statins work

A

reduce cholesterol synthesis
inhibit HMG-CoA reductase

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30
Q

How does glutathione work as a cellular defence

A

Act as reducing agent
Donates hydrogen to free radicals

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31
Q

How does HDL mature

A

progressively taking up cholesterol from peripheral tissues

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32
Q

How does HDL take up Cholesterol

A

ABCA1

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33
Q

How does LDL bind to cells

A

Express LDL receptor
apoB-100
Endocytosis

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34
Q

How does the electron transport chain act as a source of ROS

A

NADH and FADH2 provide electrons
Electrons pass through ETC and reduce oxygen
Electrons can escape and react with dissolved oxygen and form superoxide

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35
Q

How is a IDL particle produced

A

VLDL content depletes to 30%

36
Q

How is a superoxide formed from oxygen

A

Adding electron to oxygen

37
Q

How is cholesterol transported around the body

A

Cholesterol ester

38
Q

What apolipoprotein can lead to familial dyslipidaemia

A

apoE mutation to apoE2

39
Q

What apolipoprotein mutation leads to increased risk of coronary disease

A

ApoA1

40
Q

What apolipoprotein on surface of VLDL

A

ApoB100
ApoCII+ApoE(Donated by HDL)

41
Q

What are some examples of endogenous biological oxidants

A

Electron transport chain
Nitric oxide synthases
NADPH oxidases

42
Q

What are some exogenous biological oxidants(3)

A

Radiation
drugs(paracetamol)
Toxins

43
Q

What are the 2 types of damage that can occur to DNA

A

Reactive oxygen species react with the base
Reactive oxygen species react with the sugar

44
Q

What are the 2 ways apolipoproteins can adhere to phospholipid

A

Integral
peripheral

45
Q

What are the 2 ways areas ROS causes damage to protein

A

Backbone
Side chain

46
Q

What are the 3 enzymes in galactose pathway

A

Galactokinase
UDP-Galactose epimerase
Uridyl transferase

47
Q

What are the 5 different lipoprotein particles

A

Chylomicrons
VLDL
IDL
LDL
HDL

48
Q

What are the clinical signs of hypercholesterolaemia

A

Xantheslasma
Tendon Xanthoma
Corneal arcus

49
Q

What are the consequences of atherosclerotic plaque

A

reduce size of lumen
Lead to angina
Stroke
Myocardial infarction

50
Q

What are the effects of heinz bodies

A

Alter membrane rigidity
increase mechanical stress
form blister cells

51
Q

What are the routes for IDL

A

Taken up by liver via apoE to be processed
Form LDL

52
Q

What are the routes for LDL

A

Degradation in liver
become oxidised

53
Q

What are the symptoms of galactosaemia

A

hepatomegaly
renal failure
seizure
cataracts

54
Q

What can occur when protein structure changes

A

Protein degradation
Loss of function
gain of function

55
Q

What causes HDL to be taken up in the liver

A

SR-B1

56
Q

What causes Type 1 hyperlipoproteinaemia

A

Defective Lipoprotein lipase

57
Q

What causes Type IIa hyperlipoproteinaemia

A

Defective LDL
LDL levels are high

58
Q

What cofactor is required by Lipoprotein lipase

A

ApoC

59
Q

What do chylomicrons carry

A

Triacylglycerols
fat soluble vitamins
cholesterol esters
cholesterol

60
Q

What do free radical scavengers do

A

Reduce free radical damage by donating hydrogen atoms to free radicals

61
Q

What does lipid peroxidation cause in G6PDH

A

Cell membrane damage
Mechanical stress

62
Q

What enzyme is used to convert superoxide radicals to hydrogen peroxide

A

superoxide dismutase SOD

63
Q

What enzyme processes IDL in liver

A

Hepatic triglyceride lipase(HTGL)

64
Q

What enzymes used in cholesterol esterification

A

Lecithin Cholesterol Acyltransferase (LCAT)
cholesterol acyltransferase

65
Q

What goes wrong in G6PDH deficiency

A

decreased G6PDH activity
Less NADPH
Less reduction of oxidised glutathione to reduce glutathione
Less GSH
Less protection against damage from oxdiative stress

66
Q

What is a apolipoprotein

A

Apoprotein associated with lipoprotein

67
Q

what is chronic granulomatous disease

A

Inherited primary immunodeficiency disease that increases body’s susceptibility to infections caused by bacteria and fungi. Due to NADPH oxidase complex defect.

68
Q

What is corneal arcus

A

White circle around eye
If present in young it could be a sign of hypercholesterolaemia

69
Q

What is HDL

A

High density lipoproteins

70
Q

What is hypercholesterolaemia

A

High level of cholesterol in blood

71
Q

What is LDL

A

low density lipoproteins

72
Q

What is the defect in Type III hyperlipoproteinaemia

A

Apoprotein(apoE)

73
Q

What is the first response in treatment of hyperlipoproteinaemia

A

reduce cholesterol from diet
increase fibre
increase exercise
stop smoking

74
Q

What is the functional role of apolipoproteins

A

Co-factor for enzymes and ligands for cell surface receptors

75
Q

What is the importance of vitamin C in celluar defences

A

Importance in regenerating reduced form of Vitamin E

76
Q

What is the importance of vitamin E in cellular defences

A

Protection against lipid peroxidation

77
Q

What is the order of diameter for lipoproteins

A

Biggest diameter
Chylomicron
VLDL
IDL
LDL
HDL
Smallest diameter

78
Q

What is the oxidised form of glutathione

A

Glutatione disulphide

79
Q

What is the process for VLDL Metabolism

A

VLDL bind LPL on muscle and adipose
Fatty acid and glycerol release
VLDL return apoCII to HDL

80
Q

what is the role of HDL

A

Transport excess cholesterol from peripheral tissues to the liver

81
Q

What is the role of LDL

A

Provide cholesterol from liver to peripheral tissue

82
Q

What is the role of lipoprotein lipase

A

Hydrolyse triacylglycerol in lipoproteins

83
Q

What is the role of VLDl

A

Transport Triglycerides to other tissues

84
Q

What is the structural role of apolipoproteins

A

Package water insoluble lipids into soluble form

85
Q

What is xanthelasma

A

yellow patches on eyelids