Describe gluconeogenesis
Pyruvate to oxaloacetate (pyruvate carboxylase)
- Oxaloacetate to phosphoenolpyruvate (PEP carboxylase)
- To fructose 1,6 bisphosphate (lose 6 ATPs)
- To F6P (F16bP phosphotase)
- To G6P
- To glucose (G6 phosphotase)
overall glycolysis = +2ATP
overall gluconeogensis = - 6ATP
what are some general metabolic features of specialised tissues?
- muscle
- brain and nervous tissue
- adipose tissue
- heart
- liver
- muscle = periods of high ATP demand during vigorous contraction - relies on carbohydrates and fat oxidation
- brain and nervous tissue = constant high ATP requirement
- adipose tissue =
long term storage site for fats - heart = can oxidise fast and carbs
- liver = the bodys main store of carbohydrates and blood glucose
how does skeletal muscle receive energy during
light contractions :
vigorous contractions:
light - oxidative phosphorylation using oxygen and glucose
vigorous -
too much ATP is needed, so glycogen stores in the muscle is broken down and pyruvate is converted to lactate which travels to the liver
how does the brains metabolism work?
- requires a constant supply of glucose
- it cannot metabolise fatty acids
- ketone bodies can substitute for glucose
- the brain can only metabolise glucose and ketone bodies
how does the cardiac muscle respire?
- only aerobic respiration
- therefore lots of mitochondria
- can use TCA cycle substrates
like free fatty acids and ketone bodies
how does the liver respire?
- immediate recipients of nutrients are absorbed at the intestines
- Carries out many metabolic processes
- Has a role in maintaining blood glucose levels at 4.0-5.5mM
- there is a store of glycogen
what happens to excess glucose in glycolysis?
- ## G6P can be converted to glycogen which might be stores in the organ or it is transported to liver
what happens if the TCA cycle slows down because of anaerobic respiration?
- there is a build up of pyruvate
- pyruvate is then converted to lactate which can be used as an alternate fuel source
what happens to excess acetyl CoA ?
excess acetyl CoA can be converted to ketone bodies
- which might be used by the brain when there is no glucose
- or it might be converted to fatty acids and cholesterol which can then be stored
what is gluconeogenesis?
Process of making GLUCOSE or GLYCOGEN from OXALOACETATE
- this requires ATP hydrolysis
what happens in protein metabolism?
- protein is broken down into amino acids
- the amino acids can feed into the glycolysis or TCA cycle in the form of pyruvate or acetyl CoA
- The acetyl CoA that is produced can be channelled to produce fatty acids and ketone bodies
- as it is able to generate pyruvate the breakdown of protein can be used to start gluconeogenesis
what happens to the muscle cells when they have increased ATP demand?
- muscles contract more
- because contractions increase the demand for glucose and hence an increase in demand for glucose transport
- This is solved by an increase in the number of glucose transporters in the plasma membrane, transporting glucose into the muscle cell
what does adrenalin do?
- Causes an increase in muscle glycolysis - so more ATP can be produced
- increases gluconeogenesis as the demand for ATP increases more glucose is needed.
- increases the release of fatty acids so more ATP can be created
what happens in anaerobic respiration?
- TCA cycle slows and stops
- ATP demand cannot be matched by oxygen delivery • anaerobic respiration.
- muscles start breaking down their glycogen reserves
- so more glucose can enter the TCA cycle
- Because of the increased rate of glycolysis you get an accumulation of pyruvate and hence an increase in the conversion of pyruvate to lactate.
- lactate is moved to the liver to prevent the acidosis of the blood
Control of glucose metabolism in the muscle and the liver?
- this is carried out by
muscle = hexokinase 1
liver = hexokinase 4 - they both convert glucose to G6P but the difference is that they both have very different rates of reaction
describe hexokinase 1 :
muscle
- Hk I in muscles has a high glucose affinity
- Hk I activity rises rapidly in response to rising glucose concentration
- Hk I reaches max activity at quite low glucose concentrations
- highly sensitive to G6P inhibition and if G6P gets inhibited it will also get inhibited
describe hexokinase 4 (liver)
- has a low glucose affinity
- and converts glucose much slower than in the liver
- This means muscle will preferably convert glucose to G6P where glucose is available
- Hk IV is less sensitive to G6P
what does insulin do?
secreted when glucose levels rise - stimulates uptake and use of glucose and storage of glycogen and fat
what does glucagon do?
secreted when glucose levels fall - stimulates gluconeogenesis and the breakdown of glycogen and fat
what does adrenaline do?
strong and fast metabolic effects to mobilise glucose for ‘fight or flight’
what do glucocorticoids do?
steroid hormones that increase synthesis of metabolic enzymes concerned with glucose availability
what happens in T1 diabetes and T2 diabetes?
- Type I - cannot make insulin
* Type II - reduced responsiveness to insulin
what are 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
how does the body recognise glucose in the blood stream?
- the body does not recognise any glucose in the blood stream because the signalling pathway does not work
- So glucose is not taken up into the muscle or the liver.
- the body thinks it is starving
- glycogen –> glucose
- protein –> amino acids
