4 Lipid Transport metabolism and energy storage Flashcards
what is lipoprotein lipase ?
LPL is the enzyme for removing the core triacylglycerols from lipoprotein particles such as VLDLs & chylomicrons!
How are lipoproteinemia’s clinically diagnosed? (MGD LINK!)
by electrophoresis and PCR
due to diff in lipoprotein charge, weight, size and density
Treatment of hyperlipoproteinemia?
diet and lifestyle change - low fat saturated diet/ exercise
also statins - inhibit HMG CoA reductase
bile salts - lower plasma cholesterol
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
mechanisms of cell defences
superoxide dismutase/catalase
glutathione peroxidase- scavenging enzymes, catalyse H2O2 to H2O + O2
antioxidants - Vit A/C/E
what is meant by respiratory burst?
immune system (neutrophils) rapidly release ROS/RNS, produced by NADPH oxidase; *myeloperoxidase
What are ROS/RNS?
Free radicals have unpaired electrons, will take from other molecules
what is the most reactive and damaging radical?
hydroxyl radical (OH●)
formed by electron transport chain - escaped e
LDL function
Transport of cholesterol synthesised in liver to body tissues
half life is longest in blood, more susceptible to oxidative damage
chylomicrons function
transport dietary triacylglycerols from intestine to adipose tissues
VLDL function
transport of triacylglycerols synthesised in liver to adipose tissues
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
What are foam cells?
oxidised LDL taken up by macrophages transform to foam cells
causes atherosclerotic plaque build up
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
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
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
glycogen storage disease - Von Grieke
excess glycogen storage
G6P deficiency
tissue damage (excess), fasting hypoglycaemia (low blood glucose)
large liver
glycogen storage disease - McArdles disease
insufficient glycogen degradation
glycogen phosphorylase deficiency
leads to poor exercise tolerance, muscle pain/cramps
what enzyme maintains the balance b/w glycogen synthesis and breakdown?
phosphoglucomutase
gluconeogenesis?
forming glucose de novo during fasting more than 8 hours
precursors for gluconeogenesis?
pyruvate
lactate
Amino Acids
glycerol
galactose
fructose
2 enzymes essential of gluconeogenesis?
PEPCK - step 10
fructose 1,6 bisphosphate - step 3
what is lipogenesis, where does it occur and what enzyme?
fatty acid synthesis
occurs in cytoplasm
fatty acid synthase sequential addition of 2 carbons
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
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
