10 intergration of metabolic pathways Flashcards
Anabolism and catabolism
anabolism: create
catabolism: destroy
How do catabolism of proteins, fats and carbohydrates converge?
Oxidation of fatty acids, glucose, and some amino acids yield acetyl-CoA
FA -> β-oxidation
glucose -> pyruvate
amino acids -> ketogenic
Where do the acetyl-coA from fatty acids, glucose, and AA go?
Oxidation of acetyl groups in the TCA cycle
How can the TCA cycle lead to diverging anabolism?
intermediates of the TCA cycle can be removed out for biosyntehsis of carbohydrates, lipids, and amino acids
- Oxaloacetate -> carbohydrates (by -> phosphoenolpyruvate -> glucose)
- citrate removed for lipids
- oxaloacetate and α-ketoglutarate -> amino acids
What happens if TCA intermediates are syphoned out for biosynthesis?
there might not be enough intermediates to complete the TCA cycle
then there will not be enough oxaloacetate to react with acetyl-coA to form citrate = acetyl CoA metabolism will slow down and the rate of formation of ATP downstream will slow down
therefore, these intermediates must be replenished for the cycle and the central metabolic pathway to continue
How can intermediates of the TCA cycle be replenished?
By anaplerotic reactions (the red arrows)
What are the 4 major anaplerotic reactions that can happen?
- pyruvate -> oxaloacetate
- pyruvate -> malate
- phosphoenolypyruvate -> oxaloacetate (in human)
- phosphoenolypyruvate -> oxaloacetate (in plants, yeast, bacteria)
how are catabolism and anabolism regulated?
catabolic and anabolic pathways are reciprocally regulated
when one is active the other one is suppressed
Why do we want catabolic and anabolic pathways to be reciprocally regulated?
because the simultaneous degradation and synthesis of these biomolecules would be wasteful
what is different in catabolic and anabolic pathways that share the same 2 end points?
at least one of the steps use different enzymes
these enzymes will serve as the site of regulation
e.g. glycolysis vs gluconeogenesis
whats the reason for segregating paired catabolic and anabolic pathways into different cellular compartments?
conc of intermediates, enzymes and regulators can be maintained at different levels in these compartments
e.g. fatty acid catabolism occurs in mitochondria while fatty acid synthesis takes place in the cytosol
How can metabolic pathways be regulated at cellular levels?
- role and mechanism of specific enzyme
- flux of metabolites through pathways
- feedback regulation of metabolic pathways
- transport of metabolites across organelle membranes
How can metabolic pathways be regulated at whole organism level?
- metabolic activities of different tissues are regulated and integrated by growth factors or hormones acting from outside the cells
- flux of metabolites from organs to organs
What is the main fuel source of many tissues?
glucose, especially the brain
What is the process of carbohydrate metabolism in liver?
- glucose entering hepatocytes will be converted to G6P (phosphorylation)
- if G6P is not used immediately, it is dephosphorylated to release free glucose -> back into blood stream
- G6P not immediately needed is converted to liver glycogen
- Breakdown of G6P yields acetyl CoA to be oxidized for energy
- Acetyl CoA can serve as precursors of fatty acids and cholesterol
- G6P can enter the PPP giving both reducing power NADPH for biosynthesis and ribose 5 phosphate nucleotide biosynthesis
What is the process of AA metabolism in liver?
- AA are precursors for protein synthesis
- AA are passed in the blood to other organs to synthesise tissue proteins
- AA are precursors in the biosynthesis of nucleotide, hormones and other nitrogenous compounds
- AA not need are transaminated or deaminated, degraded to yield pyruvate and TCA cycle intermediates, the ammonia released is converted to urea
- Pyruvate can be converted to glucose and glycogen
- Pyruvate can be converted to acetyl-CoA
- Acetyl CoA can be oxidised via citric acid cycle
- acetyl CoA can undergo oxidative phosphorylation to get ATP
- Acetyl CoA can be converted to lipid for storage
- TCA cycle intermediates can be used for gluconeogenesis
What is the process of fatty acid metabolism in liver?
just read
What are 2 energy sources for muscle contraction?
- muscle glycogen - for heavy activity = produce lactate
- fatty acids, ketone bodies, blood glucose - for light activity or rest = produce CO2
oxygen circulation from our blood is not enough
What is O2 debt?
- after vigourous exercise, rapid breathing continues (to get over oxygen debt)
- used for oxidative phosphorylation to rebuild, proton gradient and replenish ATP inside body
- ATP, used for glucogenesis to use up lactate and restore muscle glycogen concentrations
what is Cori cycle?
the metabolic cooperation between skeletal muscle and liver
* muscles under strenuous exercise use glycogen as energy source, generating lactate via glycolysis
* during recovery, lactate is transported to liver and converted to glucose by gluconeogenesis
* the glucose is released into blood and returned to the mucles to replenish the glycogen stores
What is hormonal regulation of fuel metabolism?
concentration of blood glucose is hormonally regulated
high blood glucose triggers release of insulin
* speeds up the uptake of glucose by tissues
* favours the sotrage of fuels as glycogen and triglyceride
* inhibiting FA mobilisation in adipose tissue
low blood glucose triggers release of glucagon
* stimulates glucose release from liver glycogen
* shifts metabolism in liver and muscles to fatty acid oxidation to spare glucose for use by the brain
* in prolonged fasting, triglycerides become the principal fuel
What is the activity of the liver in the well-fed state?
- after meal, glucose, FA and AA enter the liver
- insulin is released in response to high blood glucose to stimulate glucose uptake
- excess glucose is oxidised to acetyl-coA and into FA to be exported as triglyceride to fat and muscles
- excess AA are converted to pyruvate and acetyl-coA and used for lipid synthesis
- dietary fats move form the intestine to muscle and fat via the lympathic system
what is the activity of liver in the fasting state?
- after some hours w/o a meal, the liver becomes the principle source of glucose for the brain
- liver glycogen is broken down to G1P
- G1P is converted to G6P then into free glucose which is released into the blood
- AA from degradation of proteins and glycerol from the breakdown of triglycerides are used for gluconeogenesis
- liver continues to use FA as principal fuel and excess acetyl coA is converted to ketone bodies to export to other tissues for fuel
What is metabolism during prolonged fasting or diabetes mellitus?
- protein degradation yields glucogenic AA
- Urea is exported to the kidney and excreted in urine
- TCA cycle intermediate oxaloacetate is diverted to gluconeogenesis
- glucose is experted via the blood stream to the brain
- FA (imported from adipose tissue) are oxidized as fuel, producing acetyl-CoA
- lack of oxaloacetate prevents acetyl coA entry into the TCA cycle; acetyl coA accumulates
- acetyl coA accumulation favors ketone body synthesis
- Ketone bodies are exported via the bloodstream to the brain, which uses them as fuel
- excess ketone bodies end up in urine
what is diabetes mellitus?
deficiency in the secretion or action of insulin
there are 2 major types
* type I, insulin-dependent
* type II, non-insulin dependent
- patients are unable to take glucose efficiently
- tissues then depend on FA for fuel and degrade cellular proteins to provide glucogenic AA to glucose synthesis
- uncontrolled diabetes is characterised by high levels of glucose in the blood and urine and production and excretion of ketone bodies
liver would think its starving = will turn on prolong fasting mode and start to burn protein as fuel = loose a lot of muscle mass over time
