Lecture 5 - Energy Storage & Lipid Transport Flashcards
(30 cards)
1
Q
Desc. the diff major energy stores
A
- Muscle glycogen: converted to glucose –> glycolysis
(no G-6-phosphatase) - Liver glycogen: glucose –> blood
(granules in cytoplasm)
2
Q
Desc. glycogen structure and its functions
A
- Has α-1,6 form branch points, α-1,4 join chains
- Has osmotic effect: draw in H2O
- Many branches: phosphorylated for energy
3
Q
Desc. glycogenesis
A
1. Glucose ---> G-6-P [Hexokinase, needs ATP] 2. G-6-P --> G-1-P [Phosphoglucomutase] *catalyse both ways 3. G-1-P + UTP + H20 --> UDP-glucose [G1P-uridyltransferase, needs ATP] 4. Glycogen + UDP-glucose --> Glycogen [Glycogen Synthase/Branching enzyme]
4
Q
Desc. glycogenolysis
A
- Glycogen –> G-1-P
[Glycogen Phosphorylase/De-branching enzyme] - G-1-P –> G-6-P
[Phosphoglucomutase]
5
Q
What occurs to G-6-P after formed in glycogenolysis in muscle & liver?
A
- To muscle: Glycolysis for energy
(lacks enzyme glucose-6-phosphatase) - To liver: G-6-P –> Glucose –> blood (buffer for plasma glucose)
[Glucose-6-phosphatase]
6
Q
What are some examples and causes of glycogen storage diseases? What happens when there is an excess/diminished glycogen storage?
A
- Arise from deficiency of enzymes of glycogen metabolism
- Excess: lead to tissue damage, Diminished: Hypoglycaemia & poor exercise tolerance
- Von Gierke’s disease: Glucose-6-phosphatase deficiency
- McArdle disease: muscle glycogen phosphorylase deficiency
7
Q
What are the 3 major precursors to gluconeogenesis?
A
- Lactate
- Glycerol: From lipolysis
- A.a (alanine)
8
Q
Desc. gluconeogenesis
A
- Glucogenic a.a & lactate –> pyruvate
- Pyruvate –> oxaloacetate
- Oxaloacetate –> phosphoenolpyruvate
[PEPCK] - Fructose -1,6-bisphosphate –> fructose-6-P
[fructose-1,6-bisphosphatase] [reverse is PFK, phosphofructokinase] - G-6-P –> Glucose
[G-6-Phosphatase] [Reverse is glucokinase]
9
Q
What regulates gluconeogenesis?
A
- Fructose-1,6-bisphosphatase, PEPCK (Phosphoenolpyruvate carboxykinase)
- Stimulate: glucagon, cortisol
- Inhibit: Insulin
10
Q
Why is TAGs efficient energy store?
A
- Energy content higher than carbohydrate
- Utilise in prolonged exercise, stress, starvation
11
Q
Desc. lipogenesis. (location, reaction, enzymes)
A
- Occurs mainly in liver, require ATP & NADPH
- Pyruvate enter mitochondria –> acetyl CoA & OAA –> citrate
- Citrate leaves and goes to cytoplasm –> acetyl CoA & OAA
- OAA recycled to form pyruvate again
- Acetyl CoA –> Malonyl CoA
[Acetyl-CoA carboxylase, require ATP] - Malonyl CoA –> F.A synthase complex (donate 2C) –> F.A
12
Q
What is the key regulatory enzyme of lipogenesis? What regulates it?
A
- Acetyl-CoA decarboxylase
- ⬆️insulin and citrate
- ⬇️glucagon/adrenaline & AMP
13
Q
What is the difference between fatty acid synthesis and β-oxidation?
A
Synthesis
- Add 2C (added as malonyl CoA)
- Occurs in cytoplasm
- Require NADPH and ATP (large)
- Regulated by acetyl CoA decarboxylase
- Glucagon, adrenaline inhibit & insulin stimulate
β-oxidation
- Remove 2c (removed as acetyl CoA)
- Occurs in mitochondria
- Produces NADH & FADH2
- Require ATP (small amount) to activate FA
- Regulated indirectly by amount of FA
- Insulin inhibits
14
Q
How lipids are transported in blood?
A
- 2% bound to albumin, limited capacity (~3mmol/L)
- 98% carried by:
i) Chylomicrons: Transport TAG from liver to adipose tissue
ii) VLDL: Transport TAG from liver to adipose tissue
iii) IDL: Transport cholesterol from liver to adipose tissue. Short half life, precursor for LDL
iv) LDL: Transport cholesterol from liver to tissue
v) HDL: Transport excess cholesterol from tissue to liver for disposal as bile salts/give cholesterol to cells requiring add.
15
Q
Where is cholesterol synthesised and what are its functions? What is it transported as in the blood?
A
- Synthesised in liver
- Component of membrane (modulate fluidity)
- Synthesise steroid hormones (cortisol, aldosterone, oestrogen)
- Transported as cholesterol ester
16
Q
Desc. the structure of lipoproteins
A
- Surface coat: phospholipid, cholesterol and apoproteins
- Hydrophobic core: TAG, cholesterol ester, ADEK
17
Q
Why does blood collected from a patient have a whitish-creamy appearance?
A
- Chylomicrons give creamy appearance.
- Present 4-6hr after meal
18
Q
What is the function of apolipoproteins?
A
- Co-factor for enzyme
- Ligands for cell-surface receptor
- Packaging water insol. lipid
19
Q
What is the function of lipoprotein lipase?
A
- Hydrolyse TAG in chylomicrons and VLDL to FA & glycerol
- ApoC-II cofactor
- Found on surface of endothelial cells
20
Q
Why is LDL considered ‘bad cholesterol’?
A
- Longer half life = more susceptible to oxidative damage
- Do not have apoC or E = X efficiently cleared by liver
- Macrophages engulf LDL –> foam cells accumulate in intima–> fatty streak –> atherosclerotic plaque –> invades lumen –> rupture –> thrombosis –> stroke/myocardial infarction
21
Q
How does LDL enter cell?
A
- Cell has LDL receptors –> apoB on LDL act as ligand to receptors –> endocytosis –> fuse w lysosomes –> cholesterol, FA release
22
Q
Desc. reverse cholesterol transport in HDL
A
- HDL remove cholesterol from cells –> liver
- Reduces likelihood of foam cells and atherosclerotic plaque
- ABCA1 protein facilitates transfer –> cholesterol converted to cholesterol ester by LCAT
23
Q
What happens to mature HDL?
A
- Taken up by liver
- Cells requiring additional cholesterol (steroid hormone synthesis) use scavenger receptor to obtain cholesterol from HDL
- Exchange cholesterol ester for TAG w VLDL via cholesterol exchange transfer protein (CETP)
24
Q
What is the function of Lecithin: Cholesterol Acyltransferase (LCAT)? Deficiency results in?
A
- Removal of core lipids from lipoprotein particles –> unstable due to ⬆️ratio of surface:core lipids
- LCAT converts cholesterol –> c.ester –> stable
- Deficiency: unstable lipoprotein –> failure lipid transport process
25
What are some underlying causes of hyperlipoproteinemia?
- Defective lipoprotein lipase (remove TAG from chylomicrons and VLDL)
- Defective LDL receptor
- Defective apoE --> raised IDL & chylomicron remnants
26
What are some clinical signs of hypercholesterolaemia? (⬆️cholesterol in blood)
- Xanthelasma: yellow patches on eyelids
- Tendon Xanthoma: nodules on tendons
- Corneal arcus: white circle around eye (common in old ppl, but if in young its hyper...)
27
Suggest treatment for hyperlipoproteinaemia
- 1st approach:
i) Diet = reduced cholesterol, saturated lipids & ⬆️fibre)
* fibre binds to bile salts --> excrete in faeces --> bile salts X recycled, more cholesterol removed
ii) Lifestyle = ⬆️exercise, X smoke reduce cardiovascular risk
- If X response, drugs:
i) Statin = reduce cholesterol by inhibiting enzyme HMG- CoA reductase, e.g Atorvastatin
ii) Bile salts sequestrants = bind bile salts in GI tract, more bile acid --> ⬆️cholesterol removed, e.g. Colestipol
28
What are the ranges for ideal cholesterol in body?
- Total cholesterol: HDL-C: if above 6 = high risk, the lower the better
- TAG: <2mmol in fasted sample
29
How do tissues obtain lipid needed?
- TAG = chylomicrons and VLDLs
lipoprotein lipase present on surface of cell--> hydrolyses TAG to FA & glycerol
- (in cell) FA --> TAG
[glycerol phosphate, from glucose metabolism]
- Cholesterol = LDLs (receptor mediated endocytosis)
- LDL particles bind to LDL receptors on the surface of target cells. Receptor & LDL ---> cell (endocytosis) --> fuse with lysosome --> lysosomal enzyme --> release cholesterol & receptor protein destroyed
- Cholesterol --> C. ester for storage
- When the cell has enough cholesterol = synthesis of new LDL receptors and the uptake of cholesterol is reduced
30
Desc. lipid metabolism
- Cytoplasm: fatty acid activation
FA --> FA acyl coA
(fatty acyl coa synthase)
- Enter via carnitine shuttle (controls rate of FA oxidation, inhibited by malonyl coA)
- β-oxidation: Remove 2C every time, NADH & FADH2 formed
- X ATP formed, needs O2
