Energy metabolism Flashcards
ATP-ADP cycle
ATP -> ADP + Pi , when energy is utilised in metabolic processes. Reverse reaction when energy is produced by metabolic processes (respiration)
ATP-ADP cycle products of the reaction
1) phosphate group donor and acceptor in other metabolic pathways
2) hydrogen ion donor in other metabolic pathways
3) energy for less energetically favourable processes and ‘work’
hydrogen ion donor
co-enzymes in many metabolic pathways transfer electrons in redox reactions e.g. NAD+ accepts electrons from hydrogen ion to form NADH
glucose to glucose-6-phosphate
1) phosphorylation of glucose by ATP
2) Hexokinase ( glucokinase in liver)
3) one-way process
4) commits glucose to metabolism
5) G-6-P is an intermediate in many pathways
Glucose-6-P to triose phosphates (rate limiting step)
1) isomerise G-6-P to fructose-6-P using Phosphoglucose isomerase
2) add phosphate from ATP
3) cleave into 2 phosphorylated 3-carbon compounds (triose phosphates)
4) fructose-6-phosphate to fructose-1,6-bisphosphate using enzyme phosphofructokinase-1
5) use Aldolase to convert fructose-1,6-bisphosphate to 2 molecules of glyceraldehyde-3-phosphate
G-3-P pyruvate
1) oxidation of G-3-P
2) 4 ADP phosphorylated to 4 ATP - electron transfer
3) enzymes: glyceraldehyde-3-phosphate dehydrogenase (convert 2 glyceraldehyde-3-phosphate to bisphosphoglycerate)
add phosphoglycerate kinase (convert bisphosphoglycerate to 2,3- phosphoglycerate)
4)2,3-phosphoglycerate to 2,2-phospho-glycerate using enzyme phosphoglyceromutase, then converted into 2 phospho-enolpyruvate using enolase then to 2 pyruvate using pyruvate kinase
fate of pyruvate
aerobic conditions - Krebs’ cycle
anaerobic conditions - lactate using lactate dehydrogenase
functions for glycolysis
provides ATP, generates precursors for biosynthesis, pyruvate transaminated to alanine, pyruvate substrate for fatty acid synthesis, glycerol-3-P is backbone for triglycerides
regulators of glycolysis
1) ATP & AMP - allosteric activators of PFK-1, binds to a non-catalytic site, conformational change, increases affinity for fructose-6-P
2) Citrate - allosteric inhibitor of PFK-1
3) Fructose-1,6-bisphosphate, AMP - regulates PFK-1 in liver/adipose tissue, mediates effect of insulin and glucagon, allosteric activators of PFK-1
Krebs’ cycle overview
also known as citric acid cycle and the TCA cycle
*pyruvate transported into mitochondria
* converted into acetyl co-enzyme A
*acetyl CoA condenses oxaloacetate with acetate
* oxaloacetate is regenerated
• Overall reaction:
• acetyl-CoA + 3 NAD+ + FAD + GDP + Pi + 2 H2O
• 2 CO2 + 3 NADH + FADH2 + GTP + 3 H+ + CoA
pyruvate to acetyl-CoA (krebs’ cycle)
irreversible reaction: pyruvate dehydrogenase
1) Pyruvate dehydrogenase multienzyme complex within mitochondrial matrix
2) inhibited by high concentrations acetyl-CoA and NADH
3) inactivated by phosphorylation
4) activated by phosphate removal
citrate synthase regulation (Krebs’ cycle)
1)ATP and NADH allosterically inhibit citrate synthase - both are products of Krebs’ cycle and reduce affinity of citrate synthase for its substrates, reduced rate of reaction
2) succinyl Co-A competitively inhibits citrate synthase - krebs’ cycle product, competes for binding to the active site of citrate synthase with its substrates, competitive feedback of krebs’ cycle
increased citrate inhibits citrate synthase, reduces speed of cycle
isocitrate DH regulation (krebs’ cycle)
- a key rate limiting enzyme of krebs’ cycle
- in states of increased oxidative phosphorylation demands, the rate of the krebs’ cycle reactions is increased
- however, limited by product inhibation of citrate synthase
- isocitrate dehydrogenase activation means lower citrate, citrate synthase reaction rate increased
alpha-ketoglutarate DH regulation
- another enzyme complex
- not regulated by phosphorylation/dephosphorylation
- inhibited by its products NADH and succinyl-CoA
- also inhibited by GTP, ATP, and reactive oxygen species (ROS)
- ROS are also produced by alpha-ketoglutarate DH
- activated by Ca2+ may be useful in generating ATP during intense muscle exercise
