Flashcards in Maintaining Blood Glucose Levels_Molecules Deck (89):
What conducts hormonal regulation in skeletal muscle?
What is catecholamines?
Adrenaline /Noradrenaline a.k.a epinephrine / norephinephrine
What does catecholamines do?
1) Act to stimulate phosphorylation of enzymes
2) Stimulate glycogen breakdown in liver and muscle, when fuels need to be mobilised for the energy needs of muscle (block synthesis)
3) Stimulate cAMP synthesis through beta-adrenergic receptors and raise the cytoplasmic calcium concentration through alpha1-adrenergic receptors
4) Act to increase levels of fructose 2,6-biphosphate -> stimulate glycolysis
Where are alpha1-adrenergic receptors found?
prevail in the liver
Where are beta-adrenergic receptors more important in?
What does the calcium released by the catecholamines do?
Stimulate phosphorylase kinase synergistically with cAMP
What does insulin do?
1) Stimulate glycogen synthesis in liver and skeletal muscle
2) Stimulates dephosphorylation
3) Ensures that excess carbohydrate is stored away as glycogen after a meal.
4) Through the protein kinase B cascade, it regulates glycogen metabolism
What is the reciprocal regulation that happens in the liver?
Phosphorylation and dephosphorylation of enzymes
What stimulates dephosphorylation?
What stimulates phosphorylation?
What is glycogen metabolism when there is high blood glucose?
Insulin activates glycogen synthesis and blocks glycogen breakdown
What is glycogen metabolism when there is low blood glucose?
Glucagon blocks glycogen synthesis and activates glycogen breakdown
What is ATP from glucose used for?
Major energy source for all cells
Aerobic breakdown of glucose yields how many ATP?
30 - 32 ATP
Anaerobic breakdown of glucose to lactate yields how many ATP?
What are the tissue requirements for glucose?
1) Cells without mitochondria
2) Cells of the nervous system - do have mitochondria
3) Require a continual supply of glucose from the bloodstream
What is the relationship of cells without mitochondria and glucose?
Absolute dependence on glucose for energy needs
Anaerobic glycolysis creates how many ATP?
Do cells of the nervous system have mitochondria?
What is the relationship of cells of the nervous system and glucose?
cells of the nervous system have high energy need: approx. 20% of the body's oxygen and 60% of body's glucose consumed by the brain
What is the relationship between glucose and the brain?
Glucose is sole energy source used by the brain in normal condition
What are examples of different tissue that require glucose?
1) Cardiac muscle
2) Adipose tissue
3) Skeletal muscle
What tissue can utilise glucose or fatty acid?
Muscle and adipose tissue
What is muscle and adipose tissue utilising glucose or fatty acid dependent on?
on the level of glucose in the bloodstream
What is the ideal level of glucose in the bloodstream?
Maintained between 4 - 10mM
What happens after a meal?
High blood glucose level
How does the body compensate for high blood glucose levels after a meal?
Insulin released from the pancreas
What is glucose uptake by tissue via?
Glucose transporters (GLUTs)
Where are the glucose transporters found?
on brain, RBC, liver, kidney, etc.
continually present at cell surface
Is there glucose transporters found on muscle and adipose tissue?
What is GLUT-4?
Insulin sensitive and is the glucose transporter found on the muscle and adipose tissue
What does GLUT-4 do?
Take up glucose when glucose levels in blood are high - reduce glucose levels
What is the "Fed" State?
period after the meal when there is high blood glucose level
What does insulin act to do in "fed" state
1) Stimulate glucose uptake by muscle and adipose tissue
2) Increase glycolysis
3) Increase glycogen synthesis (liver and skeletal muscle)
What happens in the liver during "fed" state?
Excess glucose used for
1) Glycogen synthesis
2) Synthesis of fatty acids - via glycolysis
What happens in the skeletal muscle in "fed" state?
Excess glucose used for glycogen synthesis
What happens in the cardiac muscle in "fed" state?
Increased glucose used to supply ATP for cell's own needs - switches from using fatty acids
What happens in adipose tissue in "fed" state?
Excess glucose used to syntheses triglycerides for storage via glycolysis
What increase in response to insulin?
Fructose-2,6-biphosphate levels increase
What happens when Phosphofructokinase-1 increase?
Overrides effects of ATP, citrate thus increasing glycolysis
What is acetyl CoA produced used to do?
Synthesise fats for storage
What are the three stage of glycogen synthesis?
What happens in the priming stage of glycogen synthesis?
What happens in the elongation stage of glycogen synthesis?
Addition of glucose to the non-reducing ends of alpha 1 - 4 chains
What happens in the branching stage of glycogen synthesis?
Formation of alpha 1 - 6 branch points
What happens in glycogen synthesis?
Enzymes embedded in the outer branches of the glycogen granule
What is UDP glucose?
"activated" glucose used in biosynthetic reactions
What is formed at the end of the priming stage of glycogen synthesis?
What is glycogen synthase?
Major regulatory enzyme in glycogen synthesis
What is glycogen synthase stimulated by?
By cellular levels of Glc-6-P
What stimulates a decrease in blood glucose?
Effects of insulin stimulate a decrease in blood glucose
What happens when insulin is released?
Blood glucose level drop
Glucagon released from pancreas
Go into fasting state
What is the fasting state?
Low blood glucose in the body
What happens when the body goes into fasting state?
Insulin levels drop
Glucagon acts on the liver
What happens when insulin levels drop?
1) Muscle and adipose tissue stop taking up glucose (GLUT-4 no longer expressed on cell surface)
2) "Spares" glucose for use of cells that requires it most
What happens when glucagon acts on the liver during fasting state?
Glucagon acts on the liver to:
1) Decrease glycolysis
2) Breakdown glycogen
3) Increase gluconeogenesis,
releasing glucose into the blood stream
What is glycogen phosphorylase?
Major regulatory enzyme in glycogen degradation
What happens during glycogen degradation?
Glc-1-P converted to Glc-6-P by phosphoglucomutase (PGM)
What does phosphoglucomutase do?
Catalyses the interconversion between Glc-1-P and Glc-6-P (both ways)
What is the allosteric control of glycogen degradation?
What happens in relationship to glycogen degradation in muscle tissue?
Inhibited by Glc-6-P and ATP; activated by AMP (glycogen in muscle used solely for muscle's own energy needs)
What does glycogen phosphorylase do in liver tissue?
Inhibited by glucose in liver tissue
What does liver do after a carbohydrate meal?
Synthesize glycogen and degrade it to free glucose during fasting
What happens in the liver during glycogen degradation?
G-6-P from glycogen breakdown is cleaved to free glucose by G-6-P, and the glucose is released into the blood for use by needy tissue including brain and blood cell
What does skeletal muscle do in regards to glycogen degradation?
Synthesise glycogen at rest and degrades it during exercise
Why can't muscle produce free glucose?
How does muscle metabolise glucose - 6 - phosphate?
By glycolysis forming lactate.
What does muscle glucose degradation form lactate?
Because glycogen degradation produces G-6-P without consuming ATP, anaerobic glycosides from glycogen produces three rather than two molecules of ATP for each glucose residue
What is the difference in liver and muscle glycolysis degradation?
- synthesised and degraded in response to feeding and fasting, therefore its level fluctuates widely in the course of a typical day
- fairly constant and becomes depleted only during vigorous and prolonged physical exercise.
What enzymes are used in glucagon in the liver?
Phosphorylase kinase phosphorylates both glycogen phosphorylase and glycogen synthase.
What happens to the liver glycogen stores in the fasting state?
Depleted after approximately 24 hour of fasting
What happens when the liver glycogen store is depleted after 24 hours of fasting?
Subsequently rely on gluconeogenesis to maintain blood glucose levels
What are the different genetic deficiencies in relation to glucose and glycogen?
1) Glycogen storage disease
2) Von Gierke disease
3) McArdle disease
What is the McArdle disease?
Deficiency of glycogen phosphorylase in muscle tissue
What is Von Gierke disease?
G-6-phosphatase deficiency - inability to convert Glc-6-P to glucose in liver
(Type 1 Glycogen storage disease)
What is glycogen storage diseases?
deficiencies in enzymes involved in glycogen degradation
What are the two forms of glycogen storage diseases?
1) Hepatic Forms
2) Myopathic forms
What happens in the hepatic form of glycogen storage disease?
What happens in the myopathic form of glycogen storage disease?
Muscle weakness and wasting
how many enzymes does gluconeogenesis use?
7 of the 10 enzymes - catalysed reactions of glycolysis
How does gluconeogenesis happen?
Specific 'by-pass' reactions at the 3 regulatory steps of glycolysis
How many ATP does gluconeogenesis consume?
Name the regulatory enzyme in gluconeogenesis
1) Pyruvate Carboxylase
2) Fructose 1,6 biphosphatase
3) Glucose - 6 - phosphatase
What happens in Von Gierke disease?
- Glc-6-P from glucose breakdown AND gluconeogenesis not converted to glucose
- no glucose released from liver to replenish blood glucose levels
- Profound fasting hypoglycaemia
How is the patient kept alive when they have Von Gierke Disease?
By regular carbohydrate feeding, day and night
Nocturnal gastric infusions of glucose or uncooked corn starch
What is the hormonal regulation in the liver during glycolysis and gluconeogenesis?
Fructose 2,6 biphosphate
What is fructose 2,6 diphosphate?
Molecule via which insulin and glucagon influence glycolysis and gluconeogenesis in the liver
What happens to glycolysis and gluconeogenesis when there is high cellular levels?