[FMS] NAM - liver and gluconeogenesis Flashcards
What is the physiological circulating and average fasting glucose concentration?
- Physiological circulating glc concentration:
3.9-6.2 mM - Average fasting:
4.4-5 mM for most adults
If it drops to 2.5 or less coma and death can result
What are the 3 advantages of glucose as a metabolic fuel?
- Water soluble , so does NOT require a carrier in the circulation
- Can cross the blood-brain barrier
- Can be oxidised anaerobically
What are the disadvantages of glucose as a metabolic fuel?
- Relatively low yield of ATP/mole compared to fatty acids
- Osmotically active
- In high concentrations can directly damage cells or lead to accumulation of toxic by-products (fructose, sorbitol)
why is glucose an important metabolic fuel
source of NADP
source of pentose sugar
source of carbon
water soluble, crosses BBB, oxidised anaerobically
why does gluconeogenesis occur
in LOW carbohydrate conditions glucose is synthesised from non-carbohydrate sources such as:
Lactate
glycerol
other monosaccharides
glucogenic amino acids (all except leu, lys)
NOT FROM FATTY ACIDS
What is gluconeogenesis
reverse of glycolysis but includes 3 irreversible reactions in glycolysis that needs to be bypassed in order for gluconeogenesis to occur
outline the steps of glycolysis and gluconeogenesis including any enzymes involved
what are the 3 irreversible reactions in glycolysis that need to be bypassed in glyconeogenesis?
ie 1st, 3rd, last
What do the blood glucose, insulin and glucagon levels in a normal person over 24 hours of normal eating behaviour look like?
INSULIN + GLUCOSE INCREASE
GLUCAGON STAYS SAME!!
what are the 3 sources of blood glucose
- Diet
- Liver glycogen
- Liver gluconeogenesis
where does gluconeogenesis and glycolysis occur
in cytosol
outline the reaction between PEP and Pyruvate
in what 2 ways is gluconeogenesis regulated?
1) Mobilisation of substrate through:
- glycerol from fat breakdown
- amino acids from muscle protein breakdown
2) activation of enzymes, such as:
- glucose-6 phosphotase, fructo-1.6- bisphosphatase, pyruvate carvoxylase, and PEP carboxykinase (the enzymes needed in gluconeogenesis)
what 2 cells are the islets of langerhans in the pancreas made up of, and what do they secrete?
- Beta cells secrete insulin
- Alpha cells secrete glucagon
remember -glucagon’ has an A in it, so its alpha, insulin doesnt have an A so by default is Beta
what is the difference between insulin and glucagon
insulin is an anabolic hormone. It promotes synthesis and storage
glucagon is a catabolic hormone. It promotes degradation of stored fuel
how does insulin maintain blood glucose in the liver
Inhibition of gluconeogenesis
activation of glycogen synthesis (glycogen synthase activated)
Increased Fatty Acid synthesis and lipid assembly
Increased aa uptake and protein synthesis
how does insulin maintain blood glucose in the muscles
Increased glucose uptake by increasing glucose transporters (GLUT4)
Increased aa uptake and protein synthesis
activation of glycogen synthesis (glycogen synthase activated)
how does glucagon maintain blood glucose
increase in blood glucose
↑ glycogenolysis and gluconeogenesis (liver).
Increase in circulating fatty acids and ketone bodies
↑ adipose tissue lipolysis, ↑fatty acid oxidation in the liver and ketone body formation.
. Decrease in plasma amino acids
↑uptake by the liver for gluconeogenesis.
What is the role of glucose in skeletal muscle?
What is the role of glucose in the heart/liver?
Why does the adipose tissue need to do glycolysis?
- The adipose tissue needs to do glycolysis because when the fat gets transferred to the adipose tissue for storage, you can’t get triaglyceroles entering the membrane
- You have to hydrolyse them in the circulation and then the fatty acids get into the adipose cell.
- You make triacylglycerol by sticking them on glycerol phosphate.
- The liver have glycerol kinase but the adipose cell does not so the only way to resynthesise the triacylglycerol is to go halfway down glycolysis, make glyceraldehyde-3-phosphate, reduce this to glycerol phosphate and you can stick the fatty acids onto it and store it.
what do erythrocytes need to maintain integrity of the erythrocyte membrane
NADPH
what pathway provides NADPH for metabolising glucose.
pentose pathway shunt AKA hexose monophosphate shunt (they can be used interchangably)
what is the function of G6PDH
glucose-6-phosphate dehydrogenase (G6PDH).
removes hydrogen from glucose
what is the most commonest human enzyme deficiency
G6PD (Glucose-6-phosphate dehydrogenase) deficiency is the commonest human enzyme deficiency.
what kind of disorder is G6PD and what sex is affected
X-linked hereditary disorder
asymptomatic
patients are predominantly male.
What are the triggers for haemolytic anaemia in people with G6PD deficiency
favism
Favism results from the ingestion of fava beans.
describe what happens after ingesting 100g of glucose over a few hours, and a few days
after ingesting glucose, glycogen is high after a few HOURS
gluconeogenesis increases over a few DAYS
what is the difference between cori cycle and glucose-alanine cycle
while both cycles involve the transport of metabolites (lactate or alanine) from muscle cells to the liver for gluconeogenesis, the key distinction lies in the specific metabolite produced in muscle cells: lactate in the Cori cycle and alanine in the Glucose-Alanine cycle.
compare the liver in its fed and fasting state.
compare the muscle in its fed state and aerobic conditions.
compare the brains pathway in its fed and fasting state.
compare the erythrocytes pathway in its fed and fasting state.
Describe the glucose tolerance curves of normal and diabetic subjects (type 1 and 2)
type 1 goes above renal threshold, so you will see it in urine
normal and type 2 is below renal threshold so you will not see it in urine
