There are various ways a cell can control a metabolic pathway:
A committed step, typically the first step in a pathway, allows a decision as to whether a pathway should be activated. This is through the first step being high energy, making it irreversible. Once this part of the pathway has been overcome, the rest of the pathway is activated. This is found in the last step of the link reaction, releasing a CO2 during the synthesis of acetyl CoA.
Another method of metabolic pathway control is feedback inhibition. This is where the final product of a pathway acts as an allosteric modulator on the first enzyme in the process. This allows for a reduction in rate to be obtained when there is sufficient product available, shutting the pathway down. A common allosteric inhibitor is ADP, preventing a pathway from being used when there is insufficient energy available, as well as preserving the ATP that is available for more urgent synthesis. Controlling isozymes in this way allows for multiple pathways to be activated or inhibited with just one inhibitor - this is common in amino acid synthesis, where common starting materials are used.
Enzyme expression control, such as with the lac operon, allows the slower control of enzyme concentration. In the lac operon, the substrate, lactose, binds to the promoter, upregulating expression. This is beneficial in bacteria, as it allows the expression of these enzymes only when needed (where there is insufficient glucose present). By regulating transcription, it ensures that glucose is always the favoured sugar for metabolism.
Controlling the concentration of the substrate is another method of changing metabolic pathway activity. Michaelis-Mentin enzyme kinetics states that a lower concentration of substrate will result in reduced enzyme activity. This could be through control of a primary metabolic pathway (such as the Krebs / Citric Acid cycle) reducing the production of the substrate required. This doesn’t always work, however, as the limiting step in a pathway will likely be another enzyme and may not result in any change to the metabolic flux. A metabolic flux analysis could be conducted to determine the impact of substrate concentration through the pathway. This would allow the identification of the limiting step and the determination of the flux coefficient.
Methods of control:
- Committed steps (CO2 release)
- Feedback inhibition (allosteric inhibitor, enzyme multiplicity (isozymes))
- Enzyme expression control (lac operon, trp repressor)
- Changing substrate concentration