Session 2 ILOs - Energy storage and lipid transport Flashcards
Describe the major energy stores in a 70kg man
Major energy stores:
Triacylglycerol
- Stored in adipose tissue, in anhydrous form
- Storage under hormonal control
Liver glycogen
- Storage of glucose in liver
- Release of glycogen can be used to raise plasma levels of glucose and used systemically
Muscle glycogen
- Storage of glucose in liver
- Release of glycogen can only be used for energy within the muscle
Muscle protein
- Protein stores in muscle tend only to be broken down as a last resort (amino acids released by proteolysis)
Describe, in outline, the reactions involved in glycogen synthesis and breakdown
Synthesis:
- Glucose is converted to G-6-P (by hexokinase - requires ATP)
- G-6-P is converted to G-1-P (by phosphoglucomutase)
- G-1-P is converted to UDP-glucose (by G-1-P uridyltransferase - requires UDP)
- Finally, UDP-glucose is added to the main glycogen structure by either alpha-1-4 or alpha-1-6 glycosidic bonds
Breakdown:
- Glycogen is converted to G-1-P (by de-branching enzyme)
- G-1-P is converted to G-6-P (by phosphoglucomutase)
- If in liver, glucose is released into the blood and for use in other tissues
- If in muscle, glucose is used for energy production IN the muscle
Compare the functions of liver and muscle glycogen
Liver glycogen:
- Storage of glucose in liver
- Glucose is released into the blood
- Release of glycogen can be used to raise plasma levels of glucose and used systemically in other tissues
Muscle glycogen:
- Storage of glucose in liver
- Release of glycogen can only be used for energy WITHIN the muscle
- Muscle lacks the enzyme glucose-6-phosphatase so G-6-P has to enter glycolysis as it can’t leave the cell
Explain the clinical consequences of glycogen storage diseases
Glycogen storage diseases = generally inherited
e. g. von Gierke’s disease = glucose-6-phosphatase enzyme deficiency
e. g. McArdle disease = muscle glycogen phosphorylase enzyme deficiency
Consequences:
- Liver or muscle can be affected
- Causes excess glycogen storage, can lead to tissue damage
- Diminished glycogen stores can lead to hypoglycaemia and poor exercise tolerance
Explain why and how glucose is produced from non-carbohydrate sources
Glucose is produced from non-carbohydrate sources by gluconeogenesis - when the glycogen stores have been used up (generally after 8 hours of fasting)
Gluconeogenesis is a way of making sure that there is a constant supply of glucose for cells e.g. RBC, neutrophils
Gluconeogenesis occurs in the liver - using either:
- Lactate, glycerol or amino acids (mainly alanine)
- PEPCK converts oxaloacetate to phosphoenolpyruvate
- Fructose-1,6-bisphosphate converts fructose-1,6-bisphosphate to fructose-6-P
- Glucose-6-phosphatase converts glucose-6-P to glucose
Explain why triacylglycerols can be used as efficient energy storage molecules in adipose tissue
Triacylglycerols can be stored in an anhydrous form in adipose tissue - TAG has twice the amount of energy content vs carbohydrates or proteins per gram
Describe how dietary triacylglycerols are processed for storage
- TAG is broken down in the small intestine by pancreatic lipases, to fatty acids and glycerol
- In the enterocytes of the intestine, fatty acids and glycerol are reabsorbed and recombined into TAG and are loaded on chylomicrons
- Chylomicrons are transported in the lymph where the lymph filters into the blood where it can be stored in adipose tissue
Describe how fatty acid degradation differs from fatty acid synthesis
Fatty acid degradation (4 key points):
- Occurs in mitochondria
- Produces acetyl-CoA
- Oxidative (produces NADH and FAD2H)
- Insulin inhibits
Fatty acid synthesis (4 key points):
- Occurs in cytoplasm
- Consumes acetyl-CoA
- Reductive (requires NADPH)
- Insulin stimulates
Describe how lipids are transported in the body
Hydrophilic lipids are transported in association with protein:
~98% as specialised lipoprotein particles - lipoprotein particles consist of non-covalent assemblies of triacylglycerols, phospholipids cholesterol, cholesterol esters and protein
~2% bound non-covalently to albumin (fatty acids)
- In the intestine, fatty acids and glycerol are reabsorbed and recombined into TAG and are loaded on chylomicrons
- Chylomicrons (carrying lipids) are transported in the lymph where the lymph filters into the blood
- Lipoprotein lipase on the capillary walls (of muscle and adipose) hydrolyses TAG into fatty acids and glycerol to be used in either the muscle for energy or stored in adipose tissue
Explain how tissues obtain the lipids they require from lipoproteins
- VLDL travels from the liver into the blood and depletes forming IDL
- IDL further depletes, forming LDL
- LDL enters the peripheral tissues by receptor mediates endocytosis
- Lysosomal degradation occurs and cholesterol, fatty acids and glycerol are released into the tissue
Explain how disturbances to the transport of lipids can lead to clinical problems (one clinical example)
Raised serum LDL = atherosclerosis
- LDL is more susceptible to oxidative damage as it’s more long lived
- Oxidised LDL is recognised and engulfed by macrophages
- If this continues, macrophages become lipid-saturated and turns into a foam cell and can accumulate in the blood vessel intima wall
- This evolves into an atherosclerotic plaque = can because angina or thrombus formation
Explain how hyperlipoproteinaemias may be treated
2 approaches:
- Initial approach
- Reduced dietary cholesterol
- Increased fibre diet
- Increase exercise
- Stop smoking to reduce CV risk - If initial approach doesn’t work!
- Give statins which reduce cholesterol synthesis
- Bile salt sequesterants, which bind bile salts which forces liver to use body cholesterol to make more bile salts
What is gluconeogenesis and why is it necessary?
Name the hormones that stimulate the process and those that inhibit it
Gluconeogenesis is the production of glucose from precursors such as lactate, pyruvate, glycerol and certain amino acids.
It is necessary to provide glucose for glucose-dependent tissues such as the CNS and red blood cells during starvation when the liver stores of glycogen have been exhausted.
Hormones:
Insulin inhibits gluconeogenesis
Cortisol and glucagon stimulate gluconeogenesis
Compare and contrast triacylglycerols and glycogen as energy storage materials in humans
Triacylglycerols and glycogen are both energy storage molecules
Triacylglycerols are the major energy storage molecules in the body (a 70kg man would normally store 10-15kg compared to 0.4 kg of glycogen)
Triacylglycerols are stored in a highly specialised tissue (adipose tissue) and glycogen is stored in tissues such as the liver and skeletal muscle which have other important functions
Triacylglycerols are a more efficient from of energy storage as they are hydrophobic and are stored in an anhydrous form while glycogen is polar and is stored with water
In addition, triacylglycerols are more reduced that glycogen and contain more stored energy per C-atom than glycogen
