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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?

- 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 :

- 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


what happens when the production of glucose is exacerbated?

- Gluconeogenesis leads to the production of glucose, which is not detected by the tissue, and hence it aggravates the hyperglycaemia.

- Triglycerides in adipose tissue are broken down releasing glycerol and free fatty acids

- these free fatty acids undego b oxidation and produce ketone bodies

- excessive production of ketone bodies leads to diabetic ketoacidosis


how do pancreatic b cells regulate hormone secretion?

- 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.

- closing the potassium ATP channels the cell becomes depolarised which causes the opening of Ca2+ ion channels so Ca2+ moves in

- this causes insulin and ZINC to be released to the blood stream



what is glucagon like peptide 1 ?

- drug that treats T2 diabetes
- but if there is an increase in plasma glucose concentrations then GLP1 accentuates the glucose response and leads to more release of insulin.


on having a meal what is the blood glucose controlled by?

- Islets of Langerhans Increased secretion of insulin and reduced secretion of glucagon

- liver
increased glucose intake

- muscle
increased glucose uptake and glycogen synthesis

- adipose tissue
increased triglyceride synthesis


what happens after a meal in terms of enzymes?

- Insulin increases the activity of Hk IV and decreases the activity of Glucose-6-Phosphatase.
Overall increase in the storage activity


what is glucagon's significance in type 2 diabetes?

- Important protection against hypoglycaemia.
- liver is the major site of action

- glucagon stimulates gluconeogenesis and glycogenolysis