The Liver and Gluconeogenesis Flashcards
Definition of glycolysis
Process of breaking down of glucose in the cytoplasm with or without oxygen
Definition of glycogenolysis
Breakdown of glycogen to glucose 1 phosphate by the sequential removal of glucose monomers via glycogen phosphorylase
Definition of gluconeogenesis
Metabolic process by which organisms produce sugars for catabolic reactions from non carbohydrate precursors
Describe the glucose requirements
Continuous
Glucose is the preferred fuel source for all tissues
Some tissues have a continuous glucose dependence
Average blood glucose conc and what happens if its too high or too low
Physiological circulating [glucose] = 3.9-6.2mM
Average fasting 4.4-5mM for most adults
2.5> = coma/death
If it rises for an extended time, dehydration, body tissue wasting and eventually death occurs
Roles of glucose
Energy source
Glucose => Pyruvate => 2ATP
Glucose => CO2 + H2O => 31 ATP
NADPH source
Needed for synthetic reactions and drug metabolism
Pentose sugar source (nucleotides, DNA)
Source of C for other sugars and glycoconjugates (mannose, galactose, glucuronic acid)
Advantages of glucose as a metabolic fuel
Water soluble, does not need a carrier in circulation
Can cross the blood brain barrier
Can be oxidized anaerobically
Disadvantages of glucose as a metabolic fuel
Relatively low yield of ATP/mole compared to FA
Osmotically active
High concentrations can directly damage cells/lead to accumulation of toxic byproducts (fructose, sorbitol)
Pathways involving glucose
Predominant pathways involving glucose are different in different tissues
All tissues use glucose
Only the liver can provide glucose for other tissues
Role of glucose in skeletal muscle
Main pathways
Function of each pathway
Glycolysis, anaerobic muscle contraction
Glycolysis/TCA, energy
Glycogen synthesis and degradation , energy store for muscle contraction
Role of glucose in heart/brain
Main pathways
Function of each pathway
Glycolysis/TCA, ENERGY
Role of glucose in adipose
Main pathways
Function of each pathway
Glycolysis
Production of glycerol phosphate for TAGS
Role of glucose in eRBC
Main pathways
Function of each pathway
Glycolysis, Energy
Pentose phosphate pathway, NADPH generation
Role of glucose in the liver
Main pathways
Function of each pathway
Glycolysis/TCA in fed state, acetyl CoA production =>FA synthesis
Pentose phosphate pathway, NADPH generation, pentoses
Glycogen synthesis/glycogenolysis, glucose glorage for other tissues
Gluconeogenesis, glucose for other tissues
Sources of blood glucose
Diet (does not last long) Liver glycogen (lasts a while) Liver gluconeogenesis (lasts the longest)
Gluconeogenesis
Occurs in carbohydrate deprivation Glucose synthesized from non carbohydrate sources in the liver Lactate Glycerol Other monosaccharides Glucogenic AA
Gluconeogenesis is not the reversal of glycolysis
Describe the pathway from pyruvate to glucose
3 irreversible reactions in glycolysis must be bypassed
- Pyruvate =(pyruvate carboxylase)=> oxaloacetate
- Oxaloacetate =(malate dehydrogenase)=> malate (as oxaloacetate cant pass through the mitochondrial membrane)
- Malate =(malate dehydrogenase)=> oxaloacetate
- Oxaloacetate =(phosphoenolpyruvate carboxykinase)=> phosphoenol pyruvate
- Fructose 1,6 biphosphate =(fructose 1,6 biphosphatase)=> fructose 6 phosphate
- Glucose 6 phosphate =(glucose 6 phosphatase)=> glucose!
2 mechanisms that are activated in gluconeogenesis
Metabolism of substrate
- glycerol from fat breakdown
- AA from muscle protein breakdown
Activation of enzymes
- Glucose 6 phosphatase
- fructose 1, 6 biphosphatase by citrate
- PEPCK
- pyruvate carboxylase by acetyl CoA
The Cori cycle (lactate) and glucose alanine cycle
What is the function of the Cori cycle?
What is the function of the glucose alanine cycle
Glucose from the liver is transported to the muscle
Glucose => G6P => Pyruvate => Acetyl CoA
Pyruvate => Alanine and lactate
Alanine and lactate => pyruvate in the liver, used in the TCA cycle
G6P can be reformed into glucose (gluconeogenesis)
Cori used to process lactate after exercise
Alanine formed from muscle degradation for energy needs
How is blood glucose maintained
Why does it need to be maintained
Insulin, glucagon, adrenaline, cortisol and glucose all signal and coordinate activity of
liver
adipose
muscle
Maintain physiological [blood glucose] needed to preserve brain function
Insulin vs glucagon
What is their function
Insulin, anabolic hormone, promotes synthesis and storage
Glucagon, catabolic hormone, promotes degradation of stored fuel
4 main metabolic effects of insulin on liver
Inhibition of gluconeogenesis
Activation of glycogen synthesis (active glycogen synthase)
Increase FA synthesis and lipid assembly
Increased AA uptake and protein synthesis
3 main metabolic effects of insulin on muscle
Increased glucose uptake by increased no of GLUT4
Increased AA and protein synthesis
Activation of glycogen synthesis (glycogen synthase active)
What are the 3 main effects of glucagon on the liver
Increased [blood glucose]
increased glycogenolysis and gluconeogenesis (in liver)
Increase in circulating fatty acids and ketone bodies
increase in adipose tissue lipolysis, increased FA oxidation in liver and ketone body formation
Decrease in plasma AA
increase in liver uptake for gluconeogenesis
Metabolic pathway of RBC and brain
RBC
-glycolysis => lactate
Brain
-glycolysis => TCA => OX PHOS all the time
WHERE DOES GLUCONEOGENESIS OCCUR
Only the liver
Why are fatty acids unable to be glucogenic?
Pyruvate => Acetyl CoA is an irreversible reaction
What is the main source of glucose in gluconeogenesis?
Lactate
