Liver: Glucose Homeostasis (gluconeogenesis) Flashcards
1) Why is glucose an important metabolic fuel?
- Continuous requirement for glucose - preferred fuel source for all tissues
- Some tissues have a continuous dependence - skeletal muscle and RBCs
- If conc drops too low (below 2.5mM), can cause coma and death
- If risen for an extended period of time (>10mM), leads to dehydration, wasting of body tissue and death
2) What are the roles of glucose?
- Source of energy for all tissues
- Source of NADP, needed for synthetic reactions (fatty acids, steroids) and drug metabolism
- Source of pentose sugars for synthetic reactions (nucleotides, DNA)
- Source of carbon for other sugars & glucoconjugates (galactose, mannose)
3) 3 advantages of glucose as a metabolic fuel
- water soluble - doesn’t require a carrier in circulation
- can cross blood-brain barrier (small enough)
- can be oxidised anaerobically (muscles, RBC)
4) 3 disadvantages of glucose as a metabolic fuel
- relatively low yield of ATP/mole compared to fatty acids
- osmotically active so needs to be stored as glycogen
- in high concentrations, can damage cells or lead to accumulation of toxic byproducts (e.g. sorbitol, fructose)
5) What are the 3 main sources of glucose to the body?
- Dietary glucose
- Recycling of glucose from other metabolites via liver gluconeogenesis
- Glucose produced from breakdown of liver glycogen
6) What are the main pathways the brain/heart, adipose tissue and erythrocytes use for energy?
- Brain/heart: glycolysis/TCA for energy
- Adipose tissue: glycolysis -> production of glycerol phosphate from TAGs (no glycerol kinase itself to make glycerol phosphate)
- Erythrocytes: glycolysis for energy and pentose phosphate pathway (shunt) for NADPH
[NADPH keeps RBC intact through oxidative stress]
7) Which non-carbohydrate sources can glucose be synthesised from, in the liver, in conditions of carbohydrate deprivation?
- Lactate
- Glycerol
- Other monosaccharides
- Glucogenic amino acids (all except leu and lys)
[NOT fatty acids]
8) Describe the stages of gluconeogenesis from pyruvate to phosphoenolpyruvate then F1,6BP
- Pyruvate –> oxaloacetate (pyruvate carboxylase)
- produces ADP + Pi
- Oxaloacetate -> phosphoenolpyruvate (PEP carboxykinase), produces CO2 and GDP
- all other reactions are directly reversible till F1,6BP
9) Describe the stages of gluconeogenesis from F1,6BP to glucose
- F1,6BP is hydrolysed to produce F6P, losing a Pi
[enzyme : fructose 1,6-bisphosphatase] - F6P -> G6P is directly reversible
- G6P is hydrolysed to produce glucose, losing a Pi
[enzyme : glucose 6-phosphatase]
10) Give the 2 main ways in which gluconeogenesis is regulated
- Mobilisation of substrate: glycerol from fat breakdown and amino acids from muscle protein breakdown
- Activation of enzymes: G6Pase, F1,6BP, PEPCK (insulin/glucagon is low), pyruvate carboxylase is activated by Acetyl CoA
11) State the 4 main compounds which control glucose maintenance
- Insulin
- Glucagon
- Glucose itself
- Adrenaline
[cortisol to a lesser extent]
12) State the purpose of these compounds and give 3 sites of action (where they signal and co-ordinate activity)
- Purpose: maintain physiological blood glucose concentrations needed to preserve brain function (and other glucose-dependant tissues)
- Sites of action are liver, adipose tissue and muscle tissue
13) Define the ‘Islets of Langerhans’ in the pancreas and which cells do they contain that are important for gluconeogenesis?
- Islets of Langerhans are a group of pancreatic cells that include alpha cells (secrete glucagon) and beta cells (secrete insulin)
- Alpha cells have receptors in the liver and adipose tissue (not muscle)
- Beta cells have receptors everywhere
[Adrenaline has receptors in the liver and muscle]
14) Which hormone inhibits gluconeogenesis and why?
Insulin as this stimulates glycogenesis, which is the formation of glycogen from glucose in order to lower blood glucose concentration. This is opposing gluconeogenesis which is therefore inhibited
15) Define the term ‘paracrine control’
- Fine-tuning of gluconeogenesis with insulin and glucagon
- Insulin is anabolic and promotes synthesis and storage
- Glucagon is catabolic and promotes degradation of stored fuel
