Saturday, July 16, 2011

Regulation of metabolism

Our body has a remarkable metabolic flexibility! Consider, for example, that we can adapt to situations as opposed as being 8-9 hours without eating (when you sleep, for example), or eat a very caloric meal.

Or else do a very intense workout in a short space of time, or a more moderate and longer, or simply stay at home. This ability to properly handle these opposites is a consequence of a strict regulation of our metabolic pathways.

The regulation of metabolic processes is, in my opinion the main point for a correct understanding of metabolism.

Before I start talking about specific regulation of each pathway, it is important to address some more general concepts ...
First, what is the regulation of metabolic pathways? It is the process by which the overall speed of each process is changed. Please note that when it comes to regulation, it does not mean necessarily inhibition, because the metabolic pathways can be activated or inhibited.
All pathways have at least one specific reaction of this process, which is irreversible. This ensures the cell two important ways:
1. Causes metabolic pathways do not occur in both directions, as a consequence only of the mass flow. That is, if a pathway produces the molecule X and the cell needs to produce more X, it is not because there is already this molecule within the cell that the same will be degraded.
2. They are used to regulate a specific metabolic pathway without affecting other processes, namely, the opposite process. To understand this we can think of two opposing processes, glycolysis (breakdown of glucose) and gluconeogenesis (glucose synthesis), for example. In cells the two processes do not occur simultaneously because there was no point being to degrade and synthesize glucose at the same time. Therefore, when one is active, the other must be inhibited. If both were catalyzed by the same enzymes, it was impossible to activate a process and inhibit another. Or both were activated or inhibited... How do we get around this problem? Using at least one enzyme specific for each process! So if I have a specific enzyme in glycolysis (there are 3 in fact ...) that does not act in gluconeogenesis, I can activate or inhibit this process without affecting the opposite.
It is these very specific and irreversible reactions that are catalyzed by enzymes called regulatory. The regulatory enzymes are enzymes that act as a kind of metabolic pathways valves, allowing "flow" more intermediaries, if you lack more product, or accumulate these intermediates, if there is enough product. The reactions catalyzed by these enzymes are often referred to as points of regulation, considering that they are the limiting steps (slower) of the process to which they belong. So if their speed is increased, the overall speed of the pathway where they are located increases, and if its speed is decreased, the overall speed of the process decreases.
There are four types of regulation of metabolic pathways:
1. Substrate availability - is the fastest method of regulation and affects all the enzymes in each pathway. Basically, if there is few substrate, the enzymes will not be able to act at its maximum speed, and if there is no substrate, the enzymes stop.
2. Allosteric regulation - is the fastest way to regulate only certain specific enzymes, called regulatory enzymes. This form of regulation requires the presence of molecules (allosteric modulators) that will interact with the enzymes, leading to structural changes that can make the enzyme faster or slower (positive and negative modulators, respectively).
3. Hormonal regulation - is a slower process than the allosteric regulation, and involves the production of hormones in response to a stimulus. Hormones are released into the bloodstream and will act on target cells. Usually its action culminates in the phosphorylation or dephosphorylation of regulatory enzymes, altering their catalytic efficiency (activated or inhibited, depending on the enzyme in question). This effect is called reversible covalent modification.
4. Changes in the concentration of enzymes - This is the slowest way of regulation and include changes in rates of synthesis and degradation of enzymes, altering their concentration. For example, if a cell wants to activate a metabolic pathway, it can do so by increasing the amount of the enzymes of this pathway. Since the substrate is not limiting, the overall rate of conversion of substrate to product will increase. The opposite effect is observed by the opposite reasoning.

Main bibliographic sources:
- Quintas A, Freire AP, Halpern MJ, Bioquímica - Organização Molecular da Vida, Lidel
- Nelson DL, Cox MM, Lehninger - Principles of Biochemistry, WH Freeman Publishers

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