Protons play a vital role in governing the structure of macromolecules, including through the charge of protein side chains, and in transportation, through hydrogen ion gradients. Intracellular mechanisms with the ability to transport, remove, or supply protons are essential in the homeostatic control of pH levels through response to deviations of hydrogen ion concentration in the surrounding environment.

pH is a logarithmic, quantitative scale, ranging from 0-14, that represents the acidity or basicity of a solution. The acidity of a solution is determined by the acid’s concentration and it’s intrinsic ability to dissociate. Therefore, we can measure the solutions acidity through the concentration of positive hydrogen ions released from the acid. One of the main constituents of a cell is the cytosol, meaning that the pH of a solution inside a cell can be measured through the concentration of hydronium ions (H3O+) when aqueous. This is because water is amphoteric, acting as both an acid and base, forming OH- and H3O+ (respectively) Due to the nature of the hydrogen ion’s abundance, we take minus the log of their concentration, to give a more manageable value. (It is also important that pH is a unit-less quantity, so you divide this value by a concentration of 1M). This value is known as pH, where a high pH indicates a basic solution, a low pH a more acidic solution and a pH of 7 a neutral solution. As you increase the pH by one unit, the concentration of hydrogen ions increases by x10 the original amount.

The pH of a solution plays an important role in the function of the cell and it’s organelles, and is therefore governed by the cell’s physiological conditions and which part of the cell we are considering. Altering the acidity of a solution can affect the chemical reactivity of molecules in cells, as many chemical reactions are driven by the interchange of hydrogen cations. It is important to maintain a constant pH, in order for chemical reactions to take place efficiently in cells. This can be regulated through different passive and active mechanisms.

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Active mechanisms include the pumping of hydrogen ions against their concentration gradient in and out of the cell to regulate the intracellular pH. This energy is obtained through the hydrolysis of ATP by the enzyme ATPase.

Passive mechanisms rely on the amount of a strong acid needed to decrease the pH by one unit, in which a strong acid can fully ionise in solution, and release one or more hydrogen cations for each original molecule of the acid. This is known as the buffering capacity, which depends on the strength of the acids found the cells metabolite pool. Buffers are molecules that can resist change to pH by controlling the amount of free floating hydrogen ions in solution. This is due to their ability to accept and donate protons in response to chemical changes in the surrounding environment. Buffers usually comprise of a weak acid and its conjugate base. . Therefore, if we add a strong acid to a solution containing a buffer, the protons released from the strong acid will be accepted by the conjugate base. If a strong base is added to the solution, the excess hydrogen ions will be associated with the conjugate base. As a weak acid can only partially dissociate to release protons, the reaction is reversible. The weak acid will therefore continually dissociate until the original equilibrium is reach and the correct pH balance is restored.

Changing the pH of the surrounding environment can also have an effect on the charge of amino acid side chains, causing a conformational change in the localization and folding of the protein, thus changing it’s overall tertiary structure, and it’s ability to function properly. 

There are four types of intermolecular forces that govern the folding of the protein, in which two can be altered through changes in the surrounding pH; Salt bridges and hydrogen bonding. Salt bridges are the result of ionic bonding between the side chains of amino acids with opposing charges. If a strong acid is added to the solution, the negatively charged side chains can act as bases by accepting the released protons and become neutralized. Contrary, if a strong base is added to the solution, the hydrogen atoms can dissociate from the positively charged side chains and be accepted by the base. This leads to a loss in the electrostatic attraction between the neutralised side chains, leading to the protein unfolding and losing it’s tertiary structure. Changing the pH can also lead to a disruption in the hydrogen bonding between side chains.

A change in the tertiary structure of the protein can affect the functioning and recognition of molecules such as enzymes, leading to them becoming inactive and denature. When considering the induced fit hypothesis, ability for the substrate to undergo catalysis is determined by the charge of the active site’s R- group. Therefore, increasing the pH results in the hydrogen ions being attracted to the negatively charged R-groups and clustering around them, reducing the ability for the substrate to bind to the active site. This can have a detrimental impact on metabolic reactions in cells.

pH levels can also govern the production of ATP. As electrons move through the  electron transport chain of the inner mitochondrial membrane, the exergonic energy released is used to actively pump hydrogen ions from the matrix to the inter membrane space. These then flow back down there concentration gradient, in which the exergonic energy is utilized again through the oxidative phosphorylation of ADP to ATP. Changes in the hydrogen ion concentration through the addition of an acid or base can effect the the equilibrium and rate of ATP production. The amount of ATP produced through ATP synthase increases after an acid is added to the solution, as more hydrogen ions are released into the intermembrane space.

It is also possible to revert mature adult cells with specialised functions to stems cells with the ability to differentiate into any cell, by adding a skin or brain cell to an acidic solution. This emphasises the importance of buffers in keeping adult cells mature and specilised


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