Thursday, November 30, 2006

Disease and pH

What is your pH?

"Whereas the median pH value in normal tissues is 7.5, in many tumor tissues the extracellular pH is more acidic, and may be as low as 5.8 (Tannock and Rotin, 1989).

"This is a consequence of a high rate of lactic acid production in tumors even under aerobic conditions (Tannock and Rotin, 1989; Boyer and Tannock, 1992; Gatenby and Gillies, 2004).
The intracellular pH of mammalian cells is normally maintained within a narrow range, i.e. from 7.1 to 7.3, and is tightly regulated by specific ion exchangers and this also holds for tumor cells (Moolenaar et al., 1984; Boyer and Tannock, 1992). As a consequence, tumor cells are exposed to a pH gradient, which can enhance the toxicity of certain weak acid drugs and impair the uptake of weak bases (Tannock and Rotin, 1989; Boyer and Tannock, 1992;
Kozin et al., 2001; Mahoney et al., 2003; Greijer et al., 2005). The idea that cancer is a disease of pH and anaerobic conditions was first proposed by Nobel laureate Otto Warburg, more than 50 years ago.

Different proteins have isoelectric points (are most stable) at different pHs. The near-neutral pI region has presumably been depleted by selective pressure -- cytoplasmic proteins are least soluble at their isoelectric point. Proteins may be evolutionarily trapped on one side of the valley or the other.

For example, human pepsin A has a pI of 3.4, consistent with its expression in the highly acidic stomach; human cytochrome c has a pI of 9.6 appropriate to binding negatively-charged membrane phospholipid.

A theory of diet related to the effects of foods on body pH:
In addition to testing bodily fluid pH, the doctor recommends: respiratory rate and breath holding ability as key indicators of the pH of body fluids. This has to with the role of CO2 in the acidification of blood. "A person with an acid imbalance will generally have a resting respiratory rate of 19 or more and if they take a deep breath will only be able to hold it for 40 seconds or less. Why? Because carbon dioxide is used by the
body to regulate pH."

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