S2: energy storage (glycogen + fat) & lipid transport

Question 1

Describe the major energy stores in a 70kg man

Answer 1

Triacylglycerol = 15kg (600,000kJ)
Liver glycogen = 0.1kg (1000kJ)
Muscle glycogen = 0.3kg (3000kJ)
Muscle protein = 6kg (100,000kJ)
In obese people, only triacylglycerol stores increase, everything else stays the same

Question 2

Describe the reaction involved in glycogen synthesis

Answer 2

Glycogenesis
Glucose + ATP -> Glucose 6 phosphate + ADP (hexokinase)
G6P Glucose 1-phosphate
G1P + UTP + H20 -> UDP-glucose + PPi (G1P uridylyltransferase)
Glycogen + UDP-glucose -> Glycogen + UDP (glycogen synthase/branching enzyme)

Question 3

Describe the reaction involved in glycogen breakdown

Answer 3

Glycogenolysis
Glycogen + Pi -> G1P + Glycogen (glycogen phosphorylase/de-branching enzyme)
G1P < — > G6P (phosphoglucomutase)
Muscle (lacks enzyme to convert G6P to glucose): glycolysis - energy production, liver: glucose - released for use by other tissues

Question 4

Compare the functions of liver and muscle glycogen

Answer 4

Liver: G6P converted to glucose and exported to blood
Liver glycogen is a BUFFER of BLOOD GLUCOSE levels
Muscle: lacks the enzyme G6 phosphatase, therefore enters glycolysis for energy production

Question 5

Explain the clinical consequences of glycogen storage diseases

Answer 5

Liver and/or muscle can be affected
Excess glycogen storage can lead to tissue damage
Diminished glycogen stores can lead to hypoglycaemia & poor exercise tolerance

Question 6

Explain why and how glucose is produced from non-carbohydrate sources

Answer 6

Gluconeogenesis = production of new glucose
Three main precursors: 1) lactate (anaerobic glycolysis), 2) glycerol (released for adipocytes breakdown of triglycerides) and 3) amino acids (mainly alanine)

Question 7

Explain why triacylglycerols can be used as efficient energy storage molecules in adipose tissue

Answer 7

Highly efficient energy store

Energy content per gram twice that of carbs or protein

Question 8

Describe how dietary triacylglycerols are processed for storage

Answer 8

Intake > requirements converted to TAG for storage
TAGs are hydrophobic and therefore stored in an anhydrous form - adipose tissue
Storage and mobilisation of TAGs is under hormonal control

Question 9

Describe how fatty acid degradation differs from fatty acid synthesis

Answer 9

Fatty acid oxidation = C2 atoms removed as acetyl CoA, occurs in mitochondria, oxidative = produces NADH and FAD2H, insulin inhibits
Fatty acid synthesis = C2 atoms added as malonyl CoA, occurs in cytoplasm, reductive = requires NADPH, insulin stimulates

Question 10

Describe how lipids are transported in the blood

Answer 10

Hydrophobic
Transported in blood bound to carriers
2% of lipids carried by albumin (limited capacity)
98% of lipids are carried as lipoprotein particles

Question 11

Describe chylomicron metabolism

Answer 11

Loaded in small intestine + apoB-48 added before entering lymphatics
Empties into left subclavian vein and acquires two new apoproteins (apoC and apoE)
apoC binds to lipoprotein lipase on adipocytes and muscle -> releases fatty acid contents
apoC dissociates and chylomicron becomes chylomicron remnant
Chylomicron remnants return to liver + taken up by receptor mediated endocytosis

Question 12

Describe hyperlipoproteinaemias

Answer 12

Raised plasma level of one or more lipoprotein classes (overproduction or under removal)
6 main classes - defects in enzymes, receptors, apoproteins

Question 13

Describe hypercholesterolaemia

Name the 3 main signs

Answer 13

High levels of cholesterol in blood
Xanthelasma = yellow patches on eyelids
Tendon xanthoma = nodules on tendon
Corneal arcus = obvious white circle around eye (in young)

Question 14

Describe IDL & LDL metabolism

Answer 14

VLDL -> IDL -> LDL
VLDL content depletes to 30%, particle becomes IDL
IDL can be taken up by liver or rebind to lipoprotein lipase to further deplete fat content
Depletes to 10% = IDL loses apoC and apoE and becomes LDL particle (high cholesterol)

Question 15

Describe HDL metabolism

Answer 15

Synthesised by liver and intestine (low TAG levels)
Have ability to remove cholesterol from cells and return it to the liver (important in blood vessels)
Mature HDL taken up by liver via specific receptors

Question 16

Functions and clinical relevance of LDLs

Answer 16

Function: take cholesterol from liver to tissues
Do not have apoC & apoE so are not efficiently cleared by liver
Clinical relevance: half-life is much longer (more susceptible to oxidative damage)
Macrophage -> foam cell -> atherosclerotic plaques

Question 17

Explain how hyperlipoproteinaemias may be treated

Answer 17

Diet = reduce cholesterol and saturated lipids in diet, increase fibre intake
Lifestyle = increase exercise, stop smoking to reduce CVS risk
If no response:
Statins = reduce cholesterol synthesis by inhibiting HMG-CoA reductase
Bile salt sequestrants = bind bile salts in GI tract, forces liver to produce more bile acids using more cholesterol

Question 18

Explain why raised serum LDL is associated with atherosclerosis

Answer 18

Oxidised LDL -> recognised by macrophages
Lipid laden macrophage = foam cell which accumulate in intima of blood vessel walls to form a fatty streak
Evolve into atherosclerotic plaque -> encroaches lumen of artery -> angina
Can cause artery to rupture -> acute thrombosis -> stroke/myocardial infarction

Question 19

Describe VLDL metabolism

Answer 19

Made in liver for purpose of transporting TAGs to other tissues
ApoB100 added during formation, apoC and apoE added from HDL particles in blood
VLDL binds to LPL on endothelial cells in muscle and adipose and starts to become depleted of triacylglycerol
Muscle = used for energy production
Adipose = fatty acids used for resynthesis of TAG + stored as fat