around 7.4. (It may be somewhat lower within cells, down to about 6.8.) This corresponds to a hydrogen ion concentration of 3.98 × 10−8 mol l−1 (since – log10 of 3.98 × 10−8 is 7.4).
The equation for ionisation of an acid HA is:
this equilibrium is described by the equation:
where Ki is the dissociation or ionisation constant and is a measure of the strength of the acid: the higher the value of Ki the stronger (i.e. the more dissociated) the acid.
Ki in the equation above relates the concentrations expressed in molar terms (e.g. mol/l). (Strictly, it is not the concentrations but the ‘effective ion concentrations’ or ion activities which are related; these are not quite the same as concentrations because of inter-ion attractions. In most biological systems, however, in which the concentrations are relatively low, it is a close approximation to use concentrations. If activities are used, then the symbol Ka is used for the dissociation constant of an acid.)
Some biological acids and their Ka values are listed in Table 1.1.1, together with a calculation of the proportion ionised at typical pH (7.4).
The calculation is done as follows (using acetic acid as an example):
(where HAc represents undissociated acetic acid, Ac− represents the acetate ion). At pH 7.4, [H+] = 3.98 × 10−8 mol l−1. Therefore,
(i.e. the ratio of ionised to undissociated acid is 440:1; it is almost entirely ionised).
The percentage in the ionised form =
| Acid | Ka | % ionised at pH 7.4 |
| Acetic, CH3COOH | 1.75 × 10−5 | 99.8 |
| Lactic, CH3CHOHCOOH | 0.38 × 10−4 | 99.9 |
| Palmitic acid, CH3(CH2)14COOH | 1.58 × 10−5 | 99.8 |
| Glycine, CH2NH2COOH (carboxyl group) | 3.98 × 10−3 | 100 |
As stated earlier, polarity is not difficult to predict in organic molecules. It relies upon the fact that certain atoms always have electronegative (electron withdrawing) properties in comparison with hydrogen. The most important of these atoms biochemically are those of oxygen, phosphorus, and nitrogen. Therefore, certain functional groups based around these atoms have polar properties. These include the hydroxyl group (–OH), the amino group (–NH2), and the orthophosphate group (–OPO32−). Compounds containing these groups will have polar properties, whereas those containing just carbon and hydrogen will have much less polarity. The presence of an electronegative atom does not always give polarity to a molecule – if it is part of a chain and balanced by a similar atom this property may be lost. For instance, the ester link in a triacylglycerol molecule (discussed below) contains two oxygen atoms but has no polar properties.
Examples of relatively polar (and thus water- soluble) compounds, which will be frequent in this book, are sugars (with many –OH groups), organic acids such as lactic acid (with a COO− group), and most other small metabolites. Most amino acids also fall into this category (with their amino and carboxyl groups), although some fall into the amphipathic (‘mixed’) category discussed below.
Another important point about polarity in organic molecules is that within one molecule there may be both polar and non-polar regions. They are called amphipathic compounds. This category includes phospholipids and long-chain fatty acids (Figure 1.4). Cell membranes are made up of a double layer of phospholipids, interspersed with specific proteins such as transporter molecules, ion channels and hormone receptors, and molecules of the sterol, cholesterol (Figure 1.5). The phospholipid bilayer presents its polar faces – the polar ‘heads’ of the phospholipid molecules – to the aqueous external environment and to the aqueous internal environment; within the thickness of the membrane is a non-polar, hydrophobic region. The physicochemical nature of such a membrane means that, in general, molecules cannot diffuse freely across it: non-polar molecules would not cross the outer, polar face and polar molecules would not cross the inner, hydrophobic region. Means by which molecules move through membranes are discussed in Chapter 2 (Box 2.1).
Figure 1.4 Chemical structures of some lipids. A typical saturated fatty acid (palmitic acid) is shown with its polar carboxylic group and non-polar hydrocarbon tail. Glycerol is a hydrophilic alcohol. However, it is a component of many lipids as its hydroxyl groups may form ester links with up to three fatty acids, as shown. The resultant triacylglycerol has almost no polar qualities. The phospholipids are derived from phosphatidic acid (diacylglycerol phosphate) with an additional polar group, usually a nitrogen-containing base such as choline (as shown) or a polyalcohol derivative such as phosphoinositol. Phospholipids commonly have long-chain unsaturated fatty acids on the 2-position; oleic acid (18:1 n-9) is shown.
