Integrated Metabolism Flashcards
Why do cell processes need to be controlled
Each cell has potential for carrying out many different chemical reactions/pathways
Many are conflicting in purpose
Co-ordinate metabolic activities within a cell
Cells do not work as individuals
Co-ordinate (integrate) metabolic activities of cells in different parts of the organism
Enable efficient utilisation of metabolites to meet current needs of the organism
What 4 ways are metabolic activities in cells controlled
Hormonal control
Substrate supply
Allosteric enzymes
Nervous control
What are the major carbohydrate metabolic processes in adipose tissue
Energy production (glycolysis, TCA)
NADPH production
Glycerol phosphate production
What are the major lipid metabolic processes in adipose tissue
Fatty acid synthesis (malonyl pathway)
Acylglycerol synthesis
Lipolysis
Energy production (b-oxidation, TCA)
What are the major carbohydrate metabolic processes in muscle tissue
Glycogen synthesis/degradation
Energy production (aerobically-glycolysis, TCA; anaerobically - glycolysis)
What are the major lipid metabolic processes in muscle tissue
Energy production (aerobically – b-oxidation, TCA)
What are the major protein metabolic processes in muscle tissue
Protein synthesis/degradation
Alanine (glutamine) production - transamination
What are the major carbohydrate metabolic processes in liver tissue
Interconversion of monosaccharides
Glycogen synthesis/degradation
Energy production (glycolysis, TCA)
Gluconeogenesis
Pentose metabolism
What are the major lipid metabolic processes in liver tissue
Fatty acid synthesis (malonyl pathway)
Acylglcerol and lipoprotein synthesis
Energy production (b-oxidation, TCA)
Ketone Body formation
What are the major protein metabolic processes in liver tissue
Transamination/deamination
Protein synthesis
Urea cycle
What happens overnight/ in the fasted post absorptive state in adipose
Pathways that prefer the breakdown/ lipolysis are more active (TAG breakdown under influence of glucagon to liberate FA to maintain energy status)
What happens in adipose tissue after a meal
Glucose is fed into adipose to supply acetyl CoA, new fatty acids are synthesised and stored as TAG, high concentration of insulins and breakdown and release of FA into the blood is suppressed
What happens in adipose under exercise conditions
FA are liberated from TAG to travel to other tissues e.g. muscle as a substrate for energy production
What happens overnight/ in the fasted post absorptive state in muscle
Energy demand of cell is stable, substrates provided from fats/lipids
Glucose is still used but predominantly lipids are used
Limited hormonal influence on energy metabolism as muscle does not have a receptor for glucagon and adrenaline is low
What happens in muscle tissue after a meal
Shift to preference for glucose as substrate, energy demand remains the same to fasted state
Not all glucose is stored as glycogen, some is oxidised immediately, some will be converted to lactate as some pyruvate is shunted away to lactate as there is an increased a,lung of pyruvate available (lactate travels to liver for gluconeogenesis)
What happens in muscle under exercise conditions
Increase in energy demand so both demand for lipid and glucose increase, lipids mainly received, from TAG breakdown in adipose, glucose influx is dicker from liver glycogen, or muscle breakdown, increased lactate production, adrenaline involvement
What happens overnight/ in the fasted post absorptive state in liver tissues
Glycogen is mainly broken down into glucose, gluconeogenesis is activated to maintain and supply glucose source, regulates blood glucose concentration, energy production main,y comes from Fa breakdown instead to maintain blood glucose concentration
What happens in liver tissue after a meal
Influx of amino acids, glucose and lipids which promote storage of glycogen, TAG (VLDL which are transported to other tissue), breakdown pathways are inhibited, increased urea production as not all amino acids necessarily used in protein synthesis
What happens in liver tissue under exercise conditions
During exercise there is an influx of lactate and glycerol into the liver which assist in regulating blood glucose concentration, majority of energy comes from utilising lipids, in duration exercise ketone bodies are produced, regulated by adrenaline and glucagon
What three major hormones are involved in energy metabolism in tissue
Insulin, glucagon and adrenaline
How do hormones control energy metabolism
act by changing activity of specific proteins via phosphorylation (kinase) and dephosphorylation (phosphorylase) (signalling cascades)
What is the role of insulin in energy metabolism
responsible for uptake and utilisation or storage of nutrients when concentrations in the blood rise. It reflects the fed state. Particularly involved in ensuring blood glucose concentrations are not too high
What is the role of glucagon in energy metabolism
responsible for raising blood glucose concentrations if they fall too low and protecting glucose by causing other nutrients (e.g. FA) to be used as a source of energy. Main target liver and adipose tissue (NOT muscle).
What is the overall effect of insulin
Glycogen synthesis is turned on because:
Glycogen synthase (GS) activated by dephosphorylation by phosphoprotein phosphatase-1 (PP1)
Glycogen degradation turned off because:
Glycogen phosphorylase (GP) is inactivated by dephosphorylation by PP1
Fatty acid synthesis is turned on because:
Acetyl-CoA carboxylase (ACC) activated by dephosphorylation by PP1
Lipolysis (breakdown of TAG) turned off because:
Hormone-sensitive lipase (HSL) activity reduced by (a) dephosphorylation by PP1 and (b) action of PDE
What is the effect of insulin on muscle
Stimulates glucose uptake, stimulates glycogenesis, inhibits glycogenolysis
What is the effect of insulin of the liver
Stimulates glycogenesis, inhibits glycogenolysis
What is the effect of insulin on fatty acid synthesis in adipose
Stimulates glucose uptake, stimulates lipogenesis, inhibits lipolysis
Describe the signalling cascade activated by glucagon
Glucagon activates
Protein Kinase A (PKA) cascade resulting in phosphorylation of:
Phosphorylase kinase which phosphorylates glycogen phosphorylase (GP, activating).
Inhibitory protein of phosphoprotein phosphatase (PP1-I or IP, activating). This results in the inhibition of phosphoprotein phosphatase- 1 activity (PP1, inhibiting.)
Pyruvate kinase (inactivating) and HSL (activating).
It also inactivates PFK2 (via PP1-I), and activates FBP2ase
What is the effect of glucagon on glycolysis and gluconeogenesis
Glucagon stimulates PKA when blood glucose is low, FBPase 2 is activated, glycolysis is inhibited and gluconeogenesis is stimulated
Describe the signalling cascade activated by adrenaline/epinephrine
Protein Kinase A (PKA) cascade resulting in phosphorylation of:
Phosphorylase kinase which phosphorylates glycogen phosphorylase (GP, activating).
Inhibitory protein of phosphoprotein phosphatase (PP1-I or IP, activating). This results in the inhibition of phosphoprotein phosphatase- 1 activity (PP1, inhibiting.)
Glycogen synthase (GS, inactivating) in muscle
Hormone-sensitive lipase (HSL, activating).
What is the effect of glucagon and adrenaline on the liver
Stimulate glycogen degradation, inhibit glycogen synthesis, increase blood glucose
What is the effect of adrenaline on muscle
No glucagon receptor.
Stimulate glycogen degradation, inhibit glycogen synthesis, increase energy from glucose.
What is the effect of insulin, glucagon and adrenalin on lipolysis in adipose tissue
Degradation of TAG is in three stages each of which releases a free fatty acid (FA)
TAG ->DAG ->MAG ->Glycerol
The enzymes responsible for the three steps are adipose triglyceride lipase (ATGL), hormone sensitive lipase (HSL) and monoglyceride lipase (MGL) respectively
Overall rate of lipolysis controlled by ATGL and HSL
Both ATGL and HSL activated by adrenalin and glucagon in adipose tissue
Both ATGL and HSL inhibited by insulin action in adipose tissue
ATGL is active when bound to ABHD5
ABHD5 normally bound to a protein perilipin
PKA, activated by adrenalin or glucagon, phosphorylates perilipin resulting in release of ABHD5 which then binds to ATGL activating it.
PKA also phosphorylates HSL activating it
Insulin activates PKB/Akt which phosphorylates and activates phosphodiesterase (PDE)
PDE degrades cAMP (2nd messenger for adrenalin and glucagon) so prevents phosphorylation of perilipin and HSL
PP1 can dephosphorylate HSL and perilipin
What is the overall effect of glucagon
Glycogen (liver) degradation is turned on because:
GP activated (a) by phosphorylation via PKA and (b) prevention of dephosphorylation by activation of PP1 inhibitor
Glycogen (liver) synthesis turned off because:
dephosphorylation of GS by PP1 inhibited
Gluconeogenesis turned on and glycolysis turned off via inactivation of PFK2 and activation of F26bPase
Glucose released from liver into blood
Lipolysis (breakdown of TAG) turned on because:
HSL activity increased by phosphorylation by PKA
What is the overall effect of adrenaline
Glycogen (liver and muscle) degradation is turned on because:
GP activated (a) by phosphorylation via PKA and (b) prevention of dephosphorylation by activation of PP1 inhibitor
Glycogen synthesis turned off because:
GS (muscle) inactivated by phosphorylation by PKA
dephosphorylation of GS by PP1 inhibited (liver, muscle)
Glucose released from liver into blood but in muscle used for glycolysis, not released into blood
Lipolysis (breakdown of TAG) turned on because:
HSL activity increased by phosphorylation by PKA
Which enzymes are active when not phosphorylated
Glycogen synthase, acetyl CoA carboxylase, phsophofructokinase 2, pyruvate kinase
Which enzymes are active in the phosphorylated form
Glycogen phosphorylase, hormone sensitive lipase, phosphoprotein phosphotase, PP1 inhibitor, Fructose-2,6-bis-phosphatse
Which enzyme can be both active and inactive in the phosphorylated form
Hormone sensitive lipase
