4 Lipid Transport metabolism and energy storage Flashcards by Cordelia Kuti

what is lipoprotein lipase ?

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

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

by electrophoresis and PCR

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

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Treatment of hyperlipoproteinemia?

diet and lifestyle change - low fat saturated diet/ exercise

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

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How can ROS cause damage?

modification of DNA bases - mispairing/mutations

heinz bodies

lipid peroxidation - hydrophobic environment disrupted

protein side chains - cause loss of function

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mechanisms of cell defences

superoxide dismutase/catalase

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

antioxidants - Vit A/C/E

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what is meant by respiratory burst?

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

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What are ROS/RNS?

Free radicals have unpaired electrons, will take from other molecules

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what is the most reactive and damaging radical?

hydroxyl radical (OH●)

formed by electron transport chain - escaped e

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LDL function

Transport of cholesterol synthesised in liver to body tissues

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

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chylomicrons function

transport dietary triacylglycerols from intestine to adipose tissues

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VLDL function

transport of triacylglycerols synthesised in liver to adipose tissues

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HDL function

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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What are foam cells?

oxidised LDL taken up by macrophages transform to foam cells

causes atherosclerotic plaque build up

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types of hyperlipoproteinemia?

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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what is glycogenesis?

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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what is glycogenolysis?

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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glycogen storage disease - Von Grieke

excess glycogen storage

G6P deficiency

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

large liver

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glycogen storage disease - McArdles disease

insufficient glycogen degradation

glycogen phosphorylase deficiency

leads to poor exercise tolerance, muscle pain/cramps

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

phosphoglucomutase

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gluconeogenesis?

forming glucose de novo during fasting more than 8 hours

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precursors for gluconeogenesis?

pyruvate
lactate
Amino Acids
glycerol
galactose
fructose

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2 enzymes essential of gluconeogenesis?

PEPCK - step 10

fructose 1,6 bisphosphate - step 3

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

fatty acid synthesis

occurs in cytoplasm

fatty acid synthase sequential addition of 2 carbons

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

activated by AMP (low energy signal)

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

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Cholesterol is a precursor of which steroid hormones (4)

TACO Testosterone Aldosterone Cortisol Oestrogen

How are heinz bodies formed

precipitate haemoglobin

How are phospholipids classified

According to polar head group

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

Ruptures Triggers thromobis and clotting cascade

How do statins work

reduce cholesterol synthesis inhibit HMG-CoA reductase

How does glutathione work as a cellular defence

Act as reducing agent Donates hydrogen to free radicals

How does HDL mature

progressively taking up cholesterol from peripheral tissues

How does HDL take up Cholesterol

ABCA1

How does LDL bind to cells

Express LDL receptor apoB-100 Endocytosis

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

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

How is a IDL particle produced

VLDL content depletes to 30%

How is a superoxide formed from oxygen

Adding electron to oxygen

How is cholesterol transported around the body

Cholesterol ester

What apolipoprotein can lead to familial dyslipidaemia

apoE mutation to apoE2

What apolipoprotein mutation leads to increased risk of coronary disease

ApoA1

What apolipoprotein on surface of VLDL

ApoB100 ApoCII+ApoE(Donated by HDL)

What are some examples of endogenous biological oxidants

Electron transport chain Nitric oxide synthases NADPH oxidases

What are some exogenous biological oxidants(3)

Radiation drugs(paracetamol) Toxins

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

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

What are the 2 ways apolipoproteins can adhere to phospholipid

Integral peripheral

What are the 2 ways areas ROS causes damage to protein

Backbone Side chain

What are the 3 enzymes in galactose pathway

Galactokinase UDP-Galactose epimerase Uridyl transferase

What are the 5 different lipoprotein particles

Chylomicrons VLDL IDL LDL HDL

What are the clinical signs of hypercholesterolaemia

Xantheslasma Tendon Xanthoma Corneal arcus

What are the consequences of atherosclerotic plaque

reduce size of lumen Lead to angina Stroke Myocardial infarction

What are the effects of heinz bodies

Alter membrane rigidity increase mechanical stress form blister cells

What are the routes for IDL

Taken up by liver via apoE to be processed Form LDL

What are the routes for LDL

Degradation in liver become oxidised

What are the symptoms of galactosaemia

hepatomegaly renal failure seizure cataracts

What can occur when protein structure changes

Protein degradation Loss of function gain of function

What causes HDL to be taken up in the liver

SR-B1

What causes Type 1 hyperlipoproteinaemia

Defective Lipoprotein lipase

What causes Type IIa hyperlipoproteinaemia

Defective LDL LDL levels are high

What cofactor is required by Lipoprotein lipase

ApoC

What do chylomicrons carry

Triacylglycerols fat soluble vitamins cholesterol esters cholesterol

What do free radical scavengers do

Reduce free radical damage by donating hydrogen atoms to free radicals

What does lipid peroxidation cause in G6PDH

Cell membrane damage Mechanical stress

What enzyme is used to convert superoxide radicals to hydrogen peroxide

superoxide dismutase SOD

What enzyme processes IDL in liver

Hepatic triglyceride lipase(HTGL)

What enzymes used in cholesterol esterification

Lecithin Cholesterol Acyltransferase (LCAT) cholesterol acyltransferase

What goes wrong in G6PDH deficiency

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

What is a apolipoprotein

Apoprotein associated with lipoprotein

what is chronic granulomatous disease

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

What is corneal arcus

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

What is HDL

High density lipoproteins

What is hypercholesterolaemia

High level of cholesterol in blood

What is LDL

low density lipoproteins

What is the defect in Type III hyperlipoproteinaemia

Apoprotein(apoE)

What is the first response in treatment of hyperlipoproteinaemia

reduce cholesterol from diet increase fibre increase exercise stop smoking

What is the functional role of apolipoproteins

Co-factor for enzymes and ligands for cell surface receptors

What is the importance of vitamin C in celluar defences

Importance in regenerating reduced form of Vitamin E

What is the importance of vitamin E in cellular defences

Protection against lipid peroxidation

What is the order of diameter for lipoproteins

Biggest diameter Chylomicron VLDL IDL LDL HDL Smallest diameter

What is the oxidised form of glutathione

Glutatione disulphide

What is the process for VLDL Metabolism

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

what is the role of HDL

Transport excess cholesterol from peripheral tissues to the liver

What is the role of LDL

Provide cholesterol from liver to peripheral tissue

What is the role of lipoprotein lipase

Hydrolyse triacylglycerol in lipoproteins

What is the role of VLDl

Transport Triglycerides to other tissues

What is the structural role of apolipoproteins

Package water insoluble lipids into soluble form

What is xanthelasma

yellow patches on eyelids