NP18 – Metabolic aspects of stress in protein and
energy metabolism
Metabolic aspects of stress
What is the nature of stress, what to do?
• Initially mostly unclear
• At first a non-specific stress-response: all options are kept open
• Later more directed to the stressor
Homeorhetic control of stress = coordinated changes in metabolism to support the same physiological state
in another way (more a dynamic approach: what does the body vs the metabolism want or nutritional
requirements)
Homeostatic control is more steady – stable way to come back to homeostasis
Neuronal action
Brain is largely involved in stress-response. Activation of HPA-axis (hypothalamus, pituitary, adrenal glands)
à glucocorticoid release à lipid breakdown increases and protein breakdown increases. More nutrients
available in system for when you need it. Fat and protein synthesis go down, glucose use goes down
= all working together to increase the availability of substrates/monomers
Mobilization of nutrients: reprioritisation - repartitioning
• Normally certain level of turnover of nutrients (glucose, fat, protein) - flux as buffer
• Stress induces unknown requirements (body doesn’t know how to tackle stress, but gets ready for it)
• Nutrients are mobilized but dangerous! E.g. increase in certain a.a. can give rise to certain effects
• Unclear whether needed
Glucose clearance test
- If you give glucose bolus à peak in glucose and lactate level constant
- If you give fructose bolus à glucose level constant and peak in lactate. At least 60% of fructose is
immediately oxidised. Not first converted to glucose (and glucose production is reduced to combine it)
- If you give sucrose (glucose + fructose) bolus à combined effect: first glucose and lactate peaks and
then back to normal
à Different cells are behaving differently upon stressors (fructose bolus)
Regulatory benefit of turnover as substrate cycle:
• Synthesis and degradation: complex processes simultaneously running
• Difficult to speed up on the short term, but we can fine tune it
, • Both can run at high rates in the substrate cycle (to have more heat produced), however without net
effect!
• Regulation by inhibition of the complementary process (the reverse process)
Protein turnover as substrate cycling
Steady state is in between catabolism and anabolism à
Stress is in catabolism (more nutrients available)
Reduction in protein synthesis à more protein breakdown
compared to protein synthesis (reduced muscle mass)
Energy expenditure upon stress:
Upon stress, metabolic rate is higher. Sometimes heat is
required (àMR up).
Flight Fight
Activity à we need energy to run away Weapons à we need proteins (e.g. antibody)
Clinical aspects
There is a poor adaptation of tissues to stress. N-balance < 0
N-excretion 150 mg N per kg per day = N/kg day (way higher excretion)
• Stress response of protein turnover
• The wound as organ
• Change in amino acid profiles depends on what’s happening: in hepatic failures Met and Phe are higher
Reprioritization of hepatic protein synthesis
• Decreases carrier proteins: Pre-albumin, albumin, transferrin
• Increase immune-active proteins à acute phase proteins (APP): C-reactive protein, α-macroglobulin
• Increase synthesis of Glutathione (scavenger of ROS), collagen
Acute phase proteins (APP)
• APP primarily synthesized by the liver
• Released into the circulation
• Various (partly unknown) functions
• Specific amino acid composition
• Up to 70 gram per day of APP produced (= 20% of daily capacity)
APP contain a lot more (2x) phenylalanine than muscle proteins. Therefore, a lot more tissue should be
degraded to support the synthesis of APP. Costs a lot of energy.
à complete shift in which a.a. are needed for APP synthesis (you breakdown muscles to have the a.a.)
Conditional essential amino acids – only in specific conditions
Demand may outstrip synthetic capacity under conditions of metabolic stress or trauma
• Glutamine: in surgical trauma and sepsis
• Arginine: at times of high protein intake + at times of high growth
• Glycine: with high intakes of some xenobiotics (excreted as glycine conjugates)
• Proline: in severe trauma (requirement for collagen synthesis, because 60% of it)
Why is there protein loss in response to trauma?
Process of body responding to a trauma leads to big losses and rapidly: the catabolic loss may be 6-7% of total
body protein over 10 days
- After a bone fractur à 900 g loss due to blood loss and catabolism (mainly)
- After a muscle wound, there is tissue loss, blood loss and catabolism à 1350 – 1900 g protein loss
energy metabolism
Metabolic aspects of stress
What is the nature of stress, what to do?
• Initially mostly unclear
• At first a non-specific stress-response: all options are kept open
• Later more directed to the stressor
Homeorhetic control of stress = coordinated changes in metabolism to support the same physiological state
in another way (more a dynamic approach: what does the body vs the metabolism want or nutritional
requirements)
Homeostatic control is more steady – stable way to come back to homeostasis
Neuronal action
Brain is largely involved in stress-response. Activation of HPA-axis (hypothalamus, pituitary, adrenal glands)
à glucocorticoid release à lipid breakdown increases and protein breakdown increases. More nutrients
available in system for when you need it. Fat and protein synthesis go down, glucose use goes down
= all working together to increase the availability of substrates/monomers
Mobilization of nutrients: reprioritisation - repartitioning
• Normally certain level of turnover of nutrients (glucose, fat, protein) - flux as buffer
• Stress induces unknown requirements (body doesn’t know how to tackle stress, but gets ready for it)
• Nutrients are mobilized but dangerous! E.g. increase in certain a.a. can give rise to certain effects
• Unclear whether needed
Glucose clearance test
- If you give glucose bolus à peak in glucose and lactate level constant
- If you give fructose bolus à glucose level constant and peak in lactate. At least 60% of fructose is
immediately oxidised. Not first converted to glucose (and glucose production is reduced to combine it)
- If you give sucrose (glucose + fructose) bolus à combined effect: first glucose and lactate peaks and
then back to normal
à Different cells are behaving differently upon stressors (fructose bolus)
Regulatory benefit of turnover as substrate cycle:
• Synthesis and degradation: complex processes simultaneously running
• Difficult to speed up on the short term, but we can fine tune it
, • Both can run at high rates in the substrate cycle (to have more heat produced), however without net
effect!
• Regulation by inhibition of the complementary process (the reverse process)
Protein turnover as substrate cycling
Steady state is in between catabolism and anabolism à
Stress is in catabolism (more nutrients available)
Reduction in protein synthesis à more protein breakdown
compared to protein synthesis (reduced muscle mass)
Energy expenditure upon stress:
Upon stress, metabolic rate is higher. Sometimes heat is
required (àMR up).
Flight Fight
Activity à we need energy to run away Weapons à we need proteins (e.g. antibody)
Clinical aspects
There is a poor adaptation of tissues to stress. N-balance < 0
N-excretion 150 mg N per kg per day = N/kg day (way higher excretion)
• Stress response of protein turnover
• The wound as organ
• Change in amino acid profiles depends on what’s happening: in hepatic failures Met and Phe are higher
Reprioritization of hepatic protein synthesis
• Decreases carrier proteins: Pre-albumin, albumin, transferrin
• Increase immune-active proteins à acute phase proteins (APP): C-reactive protein, α-macroglobulin
• Increase synthesis of Glutathione (scavenger of ROS), collagen
Acute phase proteins (APP)
• APP primarily synthesized by the liver
• Released into the circulation
• Various (partly unknown) functions
• Specific amino acid composition
• Up to 70 gram per day of APP produced (= 20% of daily capacity)
APP contain a lot more (2x) phenylalanine than muscle proteins. Therefore, a lot more tissue should be
degraded to support the synthesis of APP. Costs a lot of energy.
à complete shift in which a.a. are needed for APP synthesis (you breakdown muscles to have the a.a.)
Conditional essential amino acids – only in specific conditions
Demand may outstrip synthetic capacity under conditions of metabolic stress or trauma
• Glutamine: in surgical trauma and sepsis
• Arginine: at times of high protein intake + at times of high growth
• Glycine: with high intakes of some xenobiotics (excreted as glycine conjugates)
• Proline: in severe trauma (requirement for collagen synthesis, because 60% of it)
Why is there protein loss in response to trauma?
Process of body responding to a trauma leads to big losses and rapidly: the catabolic loss may be 6-7% of total
body protein over 10 days
- After a bone fractur à 900 g loss due to blood loss and catabolism (mainly)
- After a muscle wound, there is tissue loss, blood loss and catabolism à 1350 – 1900 g protein loss
