Consequences of biotransformation of plant secondary metabolites on acid-base metabolism in mammals-A final common pathway?

Regulation of acid-base homeostasis is essential for mammals and birds. Biotransformation and metabolism of absorbed plant secondary metabolites (PSMs) results in the production of organic acids that threaten acid-base homeostasis. Consequently these acids must be buffered and excreted from the body. The production of an acid load from detoxified PSMs should occur in herbivorous mammals and birds and with most PSMs and so may provide a unifying theme to explain many effects of PSMs on animal metabolism. Since the organic acids will be largely ionized at physiological pH, disposal of the hydrogen ion and the organic anion may proceed independently. Most hydrogen ions (H⁺) from organic acids are eliminated by one or more of three ways: (1) when they react with bicarbonate in the extracellular fluid to form carbon dioxide and the carbon dioxide is exhaled, (2) when they bind to dibasic phosphate and are excreted by the kidney as monobasic phosphate, and (3) when they are buffered and retained in the skeletal system. The secretion of phosphate ions and ammonium excretion are two ways in which the kidney replaces bicarbonate ions that have been eliminated as carbon dioxide. Secretion in the kidney tubule is an important means of excreting excessive organic anions rapidly. This process is saturable and may be subject to competition from a variety of different metabolites. Lagomorphs have limited capacity to form new bicarbonate from ammonium excretion and may therefore be obliged to excrete other cations such as sodium to balance the excretion of organic anions from PSMs. Acidemia has wide-ranging impacts on animals but browsing mammals and birds may have to break down muscle tissues to provide for urinary ammonium in order to generate bicarbonate for buffering. Acidemia also can affect the extent of urea recycling. Animals consuming browse diets may have to regulate feeding so that the rate of formation of hydrogen ions does not exceed the rate of disposal. The mechanisms by which this could occur are unknown.