Integration of metabolism Flashcards
What fuels the brain?
Continuous supply of glucose
Cannot use fatty acids
Can use ketone bodies as a partial substitute
What can hypo/hyperglycaemia do to the brain?
Hypo: faintness and coma
Hyper: irreversible damage
What fuels skeletal muscle at rest and during contraction?
Light contractions requirements met my OP
Vigorous contractions - O2 becomes a limiting factor : glycogen breakdown occurs in muscles and lactate formation occurs
What fuels the heart?
Designed for complete aerobic metabolism = rich in mitochondria
Uses TCA substrates: free fatty acids, ketone, lactate, glucose
What can happen if there is a loss of O2 supply to the heart?
Myocardiac infarction
What are the roles of the liver?
Highly metabolically active
Central role in maintaining blood glucose
Glucose storage organ
Lipoprotein metabolism
What can excess glucose 6 phosphate do?
Generate glycogen in the liver and muscle
What can excess Acetyl CoA be used for?
Generate fatty acids : stored as triglycerides in adipose
Why is lactate produced?
During extreme exercise the ATP demands of muscle outstrip the oxygen needed for aerobic respiration
= lactate made
What changes occur during fasting?
Instead of Acetyl CoA entering TCA, it is used to ketone body production
What is the pentose phosphate pathway?
Glucose 6 phosphate can be used as a source of nucleotides which also produced the bulk of NADPH needed
What does the body do, short term, to avoid hypoglycaemia?
breakdown liver glycogen = glucose
Release fatty acids from adipose
convert acetyl CoA = ketone bodies
- muscle can use the fatty acid and ketone bodies leaving more glucose for the brain
- once glycogen is depleted gluconeogenesis kicks in
What is gluconeogenesis?
Making glucose from pyruvate
Pyruvate --> Oxaloacetate --> Phosphoenol pyruvate --> G3P ( + DHAP ) --> Fructose 1,6 biphosphate --> Fructose 6 phosphate --> Glucose 6 phosphate --> Glucose
What is the cori cycle and how is it relevant to gluconeogenesis?
The Cori cycle:
generation of pyruvate from lactate in the liver and lactate dehydrogenase
Why is glycerol relevant to gluconeogenesis?
glycerol is used in generating dihydrocyyacetone phosphate ( DHAP ) which is in glycolysis and needed for gluconeogenesis
What are bypass reactions of gluconeogenesis?
Glycolysis has 3 irreversible reactions catalysed by the kinases. So these three reactions have to be bypassed on the way back to glucose
Where does the first bypass reaction take place?
Mitochondria ( the rest in cytosol )
pyruvate carboxylase to make oxaloacetate
What bypass enzyme is used for pyruvate kinase?
Phosphoenolpyruvate carboxykinase
What bypass enzyme is used against phosphofructokinase?
Fructose 1,6 biphosphate
What bypass enzyme is used against hexokinase?
Glucose 6 phosphatase
What is the difference in gluconeogenesis and glycolysis reversal?
Gluconeogenesis not a reversal at the reactions have to be bypassed with other enzymes. To make it energetically favourable.
G ( glycolysis reverse ) = +90
G ( gluconeogenesis ) = -38
What is the difference between glucogenic and ketogenic amino acids?
Glucogenic: amino acids whose skeletons can give rise to glucose via gluconeogenesis
Ketogenic: amino acids give rise to skeletons used for fatty acid and ketone body synthesis
What happens to the products of triglyceride breakdown?
Broken down into fatty acids and glycerol
Glycerol –> DHAP in gluconogenic pathway
Fatty acids –> converted to ketone bodies
What occurs during aerobic exercise?
- contractions increase ATP demands
- contractions increase glucose transport
- Muscle glycolysis increases ( adrenalin )
- gluconeogenesis increases ( adrenaline )
- fatty acids increase ( adrenaline )
As muscle contracts the demand for ATP increases, why?
Actomyosin ATPase requirements increase
What occurs during anaerobic exercise?
- ATP demand cannot be matched by O2 delivery
- transport cannot keep up with glucose demand
- muscle glycogen breakdown increases
- lactate increases
- liver uses lactate to form glucose ( recovery )
What are the differences in the hexokinase in the muscle and in the liver?
Contain isoforms of this enzyme
Maximally active at different concentrations of glucose.
Km in muscle = 0.1mM =active at low levels of glucose and inhibited by accumulating levels of glucose 6 phosphate
Km in liver = 4mM = less sensitive to blood glucose and the inhibitory effects of glucose 6 phosphate
What does glucose 6 phosphatase do?
Found in the liver not muscle
Catalyse reverse reaction to hexokinase, generating glucose from glucose 6 phosphate
What do glucocorticoids do for hormonal control of blood glucose levels?
steroid hormone which increase synthesis of metabolic enzymes concerned with glucose availability
What happens after a long fast?
- Glucagon/insulin ratio increases further
- Adipose tissue hydrolyses triglycerides to provide fatty acids for metabolism
- TCA cycle intermediates redules to provide substates for gluconeogenesis
- protein breakdown provides amino acid substrates for gluconeogenesis
- ketone bodies are produced from fatty acids and amino acids in liver to substitute partially the brain’s requirement for glucose
