Session 5: Energy storage and lipid transport Flashcards
(22 cards)
Describe major energy stores in a 70kg man
15kg triacylglycerol, 6kg protein, 0.4kg glycogen
Describe the reactions involved in glycogen synthesis
Glycogenesis
1. Glucose+ ATP= Glucose 6 phosphate + ADP using HEXOKINASE
2. Glucose 6 phosphate gives glucose 1 phosphate using PHOSPHOGLUCOMUTASE
3. Glucose 1 phosphate + UTP + H20 = UDP-glucose + P using G1P URIDYLYLTRANSFERASE.
4. Glycogen(n) + UDP glucose = Glycogen(n+1) + UDP using GLYCOGEN SYNTHASE or BRANCHING ENZYME depending on where glucose is added to chain.
Note: sythesis of glucose requires energy.
Describe reactions involved in glycogen breakdown
Glycogenolysis
1. Glycogen(n) = glucose 1 phosphate + Glycogen(n-1) using GLYCOGEN PHOSPHORYLASE or DE BRANCHING enzyme depending where glucose unit was
2. Glucose 1 phosphate = glucose 6 phosphate using PHOSPHOGLUCOMUTASE. Glucose 6 phosphate can be used in the muscles for energy production through GLYCOLYSIS and glucose is released in the liver for use by other tissues
Compare the functions of liver and muscle glycogen
Liver: Glycogen is converted to glucose 1 phosphate, glucose 6 phosphate using glucose 6 phosphatase creates glucose. Liver glycogen is a buffer of blood glucose levels
Muscle: Glycogen is converted to glucose 1 phosphate, glucose 6 phosphate, undergoes glycolysis to produce CO2, ATP, and lactate. Muscle lacks glucose 6 phophatase enzyme. G6P enters glycolysis for energy production.
Explain the clinical consequences of glycogen storage diseases
Arise from deficiency or dysfunction of enzymes of glycogen metabolism.Excess glycogen storage can lead to tissue damage. Low glycogen storage leads to hypoglycaemia and poor exercise tolerance. Examples: von Gierke’s disease(glucose 6 phosphate deficiency) and McArdle disease muscle glycogen phosphorylase deficiency)
Explain why and how glucose is produced from non-carbohydrate sources. Name the 3 major precursors and enzymes
Beyond 8 hours of fasting, liver glycogen starts to deplete and an alternative source of glucose is needed: gluconeogenesis. Occurs in liver and kidney cortex.
3 major precursors:
1. Lactate: from anaerobic glycolysis in exercising muscle and red blood cells- Cori cycle
2. Glycerol: released from adipose tissue breakdown of triglycerides.
3. Amino acids: mainly alanine.
Note: Acetyl CoA cannot be converted to pyruvate as pyruvate dehydrogenase reaction is irreversible. So acetyl CoA cannot form glucose. This is why ethanol consumption may lead to hypoglycaemia- it induces insulin secretion.
Key enzymes:
1. PEPCK: production of GDP
2. Fructose 1,6 biphosphatase: production of fructose 6 phosphate
3. Glucose 6 phosphate: production of glucose
What is the cory cycle?
Glucose in liver moves to muscle, where it produces 2 lactate, and moves through the blood to the liver. Then this cycle continues and the 2 lactate in the liver produces 2 glucose.
Explain the regulation of gluconeogenesis using the enzymes involved
Hormone: Glucagon, cortisol. When PEPCK and fructose 1,6 biphosphatase enzymes have increased activity, gluconeogenesis is stimulated.
Hormone: Insulin
When PEPCK and fructose 1,6, biphosphatase enymes have decreased activity, gluconeogenesis is inhibited.
Explain why triacylglycerols can be used as efficient energy storage molecules in adipose tissue
Excess TAG is stored in adipose tissue in anhydrous form. It is a highly efficient energy store as energy content per gram is twice that of carbohydrates or proteins. Its storage and mobilisation is controlled by hormones. Note that fat cells can be created, not destroyed.
Describe how triacylglycerols are processed for storage
look at notes for pathway
Describe how fatty acid degradation differs from fatty acid synthesis
Degradation vs synthesis
Remove C2 vs add C2
Produces acetyl CoA vs consumes acetyl CoA
Occurs in mitochondria vs occurs in cytoplasm
Oxidative- produces NADH and FAD2H vs reductive-reuires NADPH
Requires small amount of ATP to activate fatty acid vs requires large amount of ATP to drive process
Glucagon and adrenaline stimulate vs inhibit
Insulin inhibits vs insulin stimulates
Describe how lipids are transported in the blood
Lipids are hydrophobic molecules insoluble in water, and are therefore transported in blood bound carriers called lipoprotein particles. Some are carried in albumin, which has limited capacity.
Explain how tissues obtain lipids they require from lipoproteins
look at pathway on notes
What is the typical plasma concentration range of total cholesterol?
Less than 5mmol/L
What is the function of apolipoprotein
They can be integral-passing through the phospholipid bilayer or peripheral- resting on top. They package water insoluble lipids and act as a co-factor for enzymes, and as ligands for cell surface receptors.
What are the 5 different classes of mature lipoproteins
Chylomicrons, Very low density lipoproteins(VLDL), Immediate density lipoproteins(IDL), low density lipoproteins(LDL), and high density lipoproteins(HDL).
What are the functions of the 5 classes of mature lipoproteins
Chylomicrons: transports dietary TAG from the intestine to tissues like adipose tissue.
VLDL: transport of TAG synthesized in liver to adipose tissue for storage
IDL: Short lived precursor of LDL. Transports cholestrol synthesized in liver to tissues
LDL: Transports cholestrol synthesized in liver to tissues
HDL: transports excess tissue cholesterol to liver for disposal as bile salts and to cells requiring more cholestrol
Why are LDL particles more suspectible to oxidative damage?
Half life of LDL in blood is much longer than VLDL or IDL making LDL more suspectible to oxidative damage. Oxidised LDL taken up by macrophages transform into foam cells and form atherosclerotic plaques.
How does LDL enter cells
Cells that need cholesterol express LDL receptors on plasma membrane. LDL complex taken into cell by endocytosis into endosomes. Fuse with lysosomes for digestion to release cholesterol and fatty acids.
Describe the synthesis and fate of HDL particles
Synthesis: New HDL is made by liver and intestine(low TAG levels). HDL particles can also bud off from chylomicrons and VLDL as they are digested by LDL. Free apoA-I(enzyme) can acquire cholesterol from other lipoproteins and cell memebranes to form new HDL
Fate: mature HDL taken up by liver via specific receptors. Cells requiring additional cholesterol ester for steroid hormone synthesis etc can use scavenger receptors to obtain cholestrol from HDL. HDL can also exchange cholesterol ester for TAG via cholesterol exchange transfer protein(CETP)
What is hypercholesterolaemia?
High level of cholesterol in body. Leads to yellow patches on eyelids, nodules on tendon,white/blueish circle around eye(common in older peopel, a sign of disease in younger people)
What is the treatment for hyperlipoproteinaemias
- Diet: reduce cholesterol and lipid intake. Increase fibre
- Lifestyle: increase exercise, stop smoking to reduce cardiovascular risk
- If no response, use statins. Reduce cholesterol synthesis by inhibiting HMG-CoA reductase enzyme. Eg. Atorvastatin. Therefore, production of cholestrol from acetyl CoA reduces.
- If not, bind bile salts in GI tract. Forces liver to produce more bile acids using more cholesterol. eg. Colestipol
