Lecture 7 Flashcards
(14 cards)
Energy charge
Large changes in ATP is not desirable. Aim is to keep ATP at 5mM. There are instant reserves of compounds able to do substrate level phosphorylation. But, only a few seconds supply.
Creatine Phosphate
Sprinting for 5 seconds (used for energy). Able to pass P -> ADP (substrate level)
1-3 bisphosphateglycerate
2nd half of glycolysis (3C sugar phosphate + phosphate)
Phosphoenolpyruvate
2nd half of glycolysis.
More instant ATP
Adenylate kinase can take 2 ADPs to make ATP and AMP. Increase AMP = decrease energy charge in cells.
Enzymatic control
Only one or two enzymes in a pathway regulate the flow. The slowest enzyme in the pathway determines overall speed. Rate limiting step.
Enzyme kinetics
At high [substrate], minor changes [substrate] will not affect the rate of reaction. Doubling or halving [substrate] isn’t even going to affect the rate. when [substrate] approaches Km, rate of reaction may increase or decrease.
Properties of rate limiting step
Irreversible. Committed step i.e cannot go back without other enzyme. Saturated with substrate. A low Km reflects high affinity for the substrate or, the substrate concentration is much higher than Km, so the enzyme works near Vmax.
Changing the flux
- making the limiting enzyme faster or slower
- Turn the rate limiting enzyme on/off or make it work the other way
- Increase rate of transcription/translation of the RLS or change rate of degradation.
RLFs in catabolism
The rate limiting step is going to change under different circumstances e.g fed, fast, exercising, nutrients consumed and hormone control. Overriding =cofactor availability and [AMP] which is determined by ATP demand.
Phosphofructokinase
key regulatory enzyme in glycolysis. It is allosterically inhibited by high concentrations of its substrate, ATP, indicating that the cell has sufficient energy. PFK also has allosteric binding sites for AMP, which acts as an activator. When AMP binds, it signals that the cell needs more energy and promoting glycolysis. Additionally, high concentrations of citrate also inhibit PFK. Buildup of acetyl-CoA and other Krebs cycle intermediates, suggesting that energy production is already high. Citrate can diffuse into the cytoplasm and signal PFK to slow down glycolysis, preventing excess glucose breakdown.
Hexokinase: Feedback inhibition
Initial glucose trapping reaction. Inhibition by the product, G6P prevents excessive trapping and ATP wastage allowing the glucose to exit the cell. So if G6P us not being used, glucose is not trapped.
PDH-covalent modification
Inactivated by phosphorylation. Covalent attachment of phosphate which is catalysed by PDH kinase. Total amount of enzyme doesn’t change, just the ratio of phosphorylated to dephosphorylated. Reactivation by phosphatase causes phosphate release. PDH activity a valance between kinase and phosphatase.
futile cycle
When anabolic and catabolic reaction occurs at the same time e.g FA synthesis and
B O2.