Energy storage and lipid transport Flashcards
Describe the major energy stores in a 70kg man
- triacylglycerols - 15kg
- glycogen - 0.4kg
- Muscle protein - 6kg
these levels are different in an obese man who has a lot more fat (triacylglycerols)
Compare the functions of liver and muscle glycogen
Glucose is stored as glycogen primarily in the liver and skeletal muscle with a small amount stored in the brain. Liver glycogen primarily maintains blood glucose levels, while skeletal muscle glycogen is utilized during high-intensity exertion, and brain glycogen is an emergency cerebral energy source. This is because muscle lacks the enzyme glucose 6 phosphatase. G6p enters glycolysis for energy production.
Explain the clinical consequences of glycogen storage diseases
A number of inherited disorders of glycogen metabolism have been identified. This all, results from an abnormality in one or other of the enzymes of glycogen metabolism. The clinical picture and severity of the problem depends on which enzyme or tissue is affected. The major features are:
* Increased or decreased amounts of glycogen which may cause
-tissue damage if excessive storage
-Fasting hypoglycaemia (low blood glucose)
-Poor exercise tolerance
* Glycogen structure may be abnormal
* Usually liver and/or muscle are affected.
Explain why and how glucose is produced from non-carbohydrate sources
One way glucose is produced is gluconeogenesis. This is when carbohydrates is absent from the diet and instead, glucose is made initially from liver glycogen. However, this source of glucose is only sufficient for 8-10 hours. After that period of time, the body has to produce glucose by gluconeogenesis. The major site is the liver although the kidney cortex can produce glucose during starvation.
There are other intermediates that can be used to synthesise glucose such as:
* pyruvate, lactate and glycerol
* Essential and non-essential amino acids
Explain why triacylglycerols can be used as efficient energy storage molecules in adipose tissue
Triacylglycerols are a very efficient method of storing energy, as they can be stored in bulk in an anhydrous form in adipose tissue. They are highly calorific and function largely as a store of fuel molecules (fatty acids and glycerol) which can be mobilised during prolonged aerobic exercise,
stress situations such as starvation and during pregnancy. Storage is under hormonal control being promoted by insulin and reduced by glucagon, adrenaline, cortisol, growth hormone and thyroxine.
Describe how dietary triacylglycerols are processed for storage
?
Describe how fatty acid degradation differs from fatty acid synthesis
Fatty acids are synthesised from acetyl CoA at the expense
of ATP and NADPH. The pathway occurs in the cytoplasm
and is presented as:
Fatty acid synthesis is not simply a reverse of fatty acid
degradation and it occurs via a totally different pathway.
Both processes consist of a cycle of reactions that either
increase or decrease the length of the fatty acid carbon
chain by c2 per turn of the cycle
Describe how lipids are transported in the blood
Lipids that have either come from the diet or have been synthesised in the body are being transported to tissues for storage or utilisation. Since lipids are insoluble, the must be carried in the plasma in association with protein. Most of the lipid is carried as highly specialised non-covalent assemblies known as lipoprotein particles, whilst some are carried bound non-covalently to albumin.
Explain how disturbances to the transport of lipids can leads to clinical problems
Cholesterol or lipids can remain in the blood plasma/tissues instead as the lipoproteins aren’t working efficiently. This can causes an increased risk of atherosclerosis’ as there’s sac increased risk of an ageing forming. This can lead to a myocarditis infarction or coronary heart diseases.
Explain how tissues obtain the lipids they require from lipoproteins
Chylomicrons - Transport dietary triacylglycerol fro, the intestine to tissues such as adipose tissue
VLDL - Transport of triacylglycerol synthesised in liver to adipose tissue for storage
IDL - Short-lived precursor for LDL. Transport of cholesterol synthesised in the liver to tissues
LDL - Transport of cholesterol synthesised in the liver to tissues
HDL - Transport of excess tissue cholesterol to liver for disposal as bile salts and to cells requiring additional cholesterol
Explain how hyperlipoproteinaemias may be treated
*Diet and lifestyle modification E.g. increased exercise which reduces the risk factors of atherosclerosis and coronary heart disease.
*Statins such as atorvastatin which reduces the synthesis of cholesterol in the liver by inhibiting the enzyme HMG-CoA reductase
A secondary effect of statins is the increase the expression of lipoprotein lipase which lowers plasma cholesterol by increasing its disposal in the body
Explain Chylomicron metabolism
Chylomicrons are loaded in the small intestine and apoB-48 is added before it enters the lymphatic system. It acquires two more apoproteins in the left subclavian vein. apoC binds to lipoprotein lipase on adipocytes and muscle. Released fatty acids enter cells depleting chylomicron of its fat content. When the triglyceride is reduced to around 20%, the chylomicron becomes a chylomicron remnant. This returns to the liver where LDL receptor on hepatocytes bind to apoE and the remnant is taken up by receptor mediated endocytosis
Explain VLDL, IDL, and LDL metabolism
VLDL binds to lipoprotein lipase (LPL), on endothelial cells, and starts to be depleted of triacylglycerol. As the triacylglycerol content drops some, the VLDL dissociates from the LPL enzyme and returns to the liver. If the VLDL content depletes to 30%, it will become a short lived IDL particle. IDL particles can then be taken up by the liver or rebind to LPL enzyme to further deplete in TAG content. When the depletion drops to around 10%, the IDL loses apoC and apoE and becomes an LDL particle
Explain how raised LDL concentrations are associated with atherosclerosis
Raised LDL concentrations, means that more cholesterol is transported from the liver to the tissues which increases blood cholesterol, which increases the risk of an atheroma forming, which also increases the risk of CHD
Describe in outline the reactions involving glycogen synthesis
Glycogen synthesis (Glycogenesis)
Step 1) Glucose + ATP - Glucose 6 P + ADP
Catalysed by hexokinase (glucokinase in liver)
Step 2) Glucose 6-P <-> Glucose 1-P
Catalysed by phosphoglucomutase
Step 3) Glucose 1-P + UTP + H2O -> UDP-glucose + 2pi
Step 4) Glycogen (in residues) + UDP-glucose -> glycogen (n+1 residues) + UDP
