W5 Energy I Flashcards
Catabolism
Breakdown of complex molecules to release energy or carry out mechanical work
Anabolism
Synthesis of new molecules from less complex components
How much ATP do we need?
Total ATP in body = 100g
Total amount of energy available from the hydrolysis of ATP is 65kj/mole
Usage at rest = 40Kg/24hour
Usage during exercise = 0.5Kg/minute
Glycolysis
Glucose to G6P (ATP used) (Hexokinase)
G6P to F6P
F6P into fructose 1,6 bisphosphate (ATP used) (Phosphofructokinase)
Fructose 1,6 bisphosphate into dihydroxyacetone phosphate + glyceraldehyde 3 phosphate (these 2 are intermediates in equilibrium w/each other)
3 carbon intermediate into phosphoenol pyruvate (2 * ATP + NADH made)
Phosphoenol into pyruvate (2 * ATP made) (Pyruvate kinase)
2 pyruvate made
2 ATP
2 NADH
Regulation of trancription
Enzymes catalysing irreversible reactions = potential sites
for regulation
Activity of such enzymes can be regulated by:
Reversible binding of allosteric effectors
Covalent modification
Transcription
Phosphorylation
Can have +/- effect
G6P inhibits G to G6P
ATP, citrate and H+ inhibit F6P to fructose 1,6 bisphosphate (AMP stimulates)
ATP inhibits phosphoenol pyruvate into pyruvate
Regulation of muscle glycolysis to meet need for ATP
ADP + ADP → ATP + AMP (adenylate kinase)
AMP signal for low energy state
PFK is the most important control point
High concentrations of ATP inhibit PFK
by lowering the affinity for fructose 6 phosphate
Also inhibited by low pH
Inhibition of PFK leads to inhibition of hexokinase
Why AMP not ATP
AMP much better signal of activity than ATP itself because ADP will be present anyway for resynthesis of ATP
Why AMP and not ADP
ATP can be made from ADP by adenylate kinase 2ADP gives ATP + AMP therefore AMP is a better indicator of energy state
Regulation of glycolysis in the liver
High concentrations of ATP inhibit PFK
PFK is inhibited by citrate
PFK is stimulated indirectly by a build up of F6P
Hexokinase is inhibited by G6P
But the liver also has glucokinase which is not inhibited by G6P
Low pH is not a problem as the liver does not normally produce lactate
Example of feed forward regulation in liver
Indirect activation by F6P which is converted to F26bisP when blood glucose is high
Tumours and exercising muscles have what in common
Anaerobiccally respire
Growth of tumour outweighs/outstetches the availibility of oxygen delivered by blood supply
Lactate
Toxic as acidic
H+ inhibit
So lactate exported into blood + taken up by liver
Why do tumours use glycolysis
When tumours outgrow their blood supply oxygen delivery is reduced, tumour cell metabolism reverts to glycolysis
Reduction in O2 leads the
activation of the transcription
Factor HIF-1α (hypoxia-inducible factor)
HIF-1α regulates the expression
of a number enzymes in the
glycolytic pathway + blood vessel growth
Functions of glycolysis
Degrades glucose to generate ATP and provides building blocks for the synthesis of cellular components
Three non-reversible steps phosphofructokinase is inhibited by ATP and citrate and activated by AMP and fructose 2-6 bisphosphate
Hexokinase inhibited by G6P. ATP and alanine inhibits PK.
PK activity max when energy charge is low and glycolytic intermediates accumulate