Met 9 Flashcards
what type of metabolism occurs in the brain
Glucose Dependent Metabolism
Requires continuous supply of GLUCOSE
CANNOT METABOLISE FATTY ACIDS
KETONE BODIES can partially substitute for glucose
IMPORTANT: THE BRAIN CAN ONLY METABOLISE GLUCOSE AND KETONE BODIES
What is Gluconeogenesis
Process of making GLUCOSE or GLYCOGEN from OXALOACETATE (from the TCA cycle)
Essentially only done in the Liver
Oxaloacetate to phosphoenolpyruvate then the reverse of glycolysis.
Uses 6 ATP
Describe protein metabolism
Protein is broken down into amino acids.
Amino acids can feed into the Glycolysis or the TCA cycle in the form of pyruvate, acetyl CoA and other substrates in the TCA cycle.
It is excreted as urea.
The acetyl CoA that is produced can be channelled to produce fatty acids and ketone bodies which can either be stored, used in the heart or the brain.
As it is able to generate pyruvate, the breakdown of protein can be used to START GLUCONEOGENESIS.
Fat metabolism
Triglycerides are broken down into fatty acids and glycerol which enter glycolysis and the TCA cycle in the form of ACETYL CoA.
So, pyruvate is not produced when fats are used in respiration.
As a by-product you also form ketone bodies which can be used by the heart and the brain.
Some of the substrates generated by the TCA cycle can be moved into pathways to generate amino acids.
As there is no generation of pyruvate and hence no conversion of pyruvate to oxaloacetate, the lack of accumulation of oxaloacetate means that you CANNOT GENERATE GLUCOSE VIA GLUCONEOGENESIS.
What does adrenalin do?
Adrenalin -
increases gluconeogenesis as the demand for ATP increases and needs are not met by glucose in the blood stream alone
increases the release of fatty acids - more fatty acids available for ATP generation
Describe what happens in anaerobic respiration
ATP demand cant be matched by o2 delivery
Transport can not keep up with the demand for glucose
Muscle glycogen breakdown increases
lactate increases
liver uses lactate to form glucose
what is hexokinase I
Convert glucose to G6P
Hk I in muscles has a high glucose affinity
Hk I activity rises rapidly in response to rising glucose concentration
Hk I reaches close to maximum activity at relatively low glucose concentrations
It is highly sensitive to G6P inhibition
If G6P accumulates (e.g. due to slowing down of TCA cycle in anaerobic conditions) Hk I will be inhibited.
What is hexokinase IV
Convert glucose to G6P
Hk IV has a low glucose affinity
Rate is 1/2 maximal at 4mM
This means muscle will preferably convert glucose to G6P where glucose is available. This reaction is much slower in the liver in comparison to the muscle at the same glucose concentrations.
Hk IV is less sensitive to G6P
So G6P can accumulate but Hk IV will continue to convert glucose to G6P.
4 hormones involved in metabolism control
Insulin - secreted when glucose levels rise - stimulates uptake and use of glucose and storage of glycogen and fat
Glucagon - secreted when glucose levels fall - stimulates gluconeogenesis and the breakdown of glycogen and fat
Adrenaline - strong and fast metabolic effects to mobilise glucose for ‘fight or flight’
Glucocorticoids - steroid hormones which increase synthesis of metabolic enzymes concerned with glucose availability.
Different types of diabetes
Type I - cannot make insulin
Type II - reduced responsiveness to insulin
Complications of diabetes
Hyperglycaemia - causing progressive tissue damage
Increase in plasma fatty acids and lipoproteins - possible cardiovascular complications
Increase in ketone bodies - possible acidosis
Hypoglycaemia - possible coma if insulin dosage is not correctly controlled
Regulation of hormone secretion in pancreatic b cells
Glucose transported into the beta cell and is metabolised to produce ATP.
ATP is also a signalling molecule within the cell.
ATP binds to the potassium ATP channel at the cell surface and regulates its function.
By closing the potassium ATP channels the cell becomes depolarised which causes the opening of Ca2+ ion channels.
This causes the entry of Ca2+ into the cell from the outside.
The increase in calcium ion concentration in the cell leads to the mobilisation of insulin from within the cell to the cell surface and release into the blood stream.
Cells also release Zinc as well as insulin.
GLP-1 (Glucagon Like Peptide 1) - drug that’s important in the treatment of type II diabetes - it works in conjunction with glucose - when you administer mimetics of GLP-1 they don’t do anything in terms of insulin release but if there is an increase in plasma glucose concentrations then GLP1 accentuates the glucose response and leads to more release of insulin.
With Type II diabetics - GLP1 can make their beta cells more active so they release more insulin into the blood stream.
What happens in your body straight after you have a meal
Islets of Langerhans - Increased secretion of insulin and reduced secretion of glucagon
Liver - Increased glucose uptake - used for glycogen synthesis and glycolysis
Muscle - Increased glucose uptake and glycogen synthesis
Adipose Tissue - Increased triglyceride synthesis
Insulin increases the activity of Hk IV and decreases the activity of Glucose-6-Phosphatase.
Overall increase in the storage activity (glycogen and fat synthesis).
What happens in your body a while after you have a meal
Islets of Langerhans - increased glucagon secretion + decreased insulin secretion
Liver - glucose production + glycogen breakdown + gluconeogenesis
Utilisation of fatty acid breakdown as alternative substrate for ATP production (important in preserving glucose for the brain)
Adrenaline - has similar effects on the liver + stimulates glycogen breakdown and glycolysis in skeletal muscle + fat lipolysis in adipose tissue
What happens After prolonged fasting
Glucagon/Insulin ratio increases further
Adipose Tissue - hydrolyses triglycerides to provide fatty acids for metabolism
TCA cycle intermediates are reduced in amount to provide substrates for gluconeogenesis.
Protein breakdown provides amino acid substrates for gluconeogenesis.
Liver - produces ketone bodies from fatty acids and amino acids to partially substitute the brains requirement for glucose.
