The missing hydrogen ion, part-1: Historical precedents vs. fundamental concepts

Area of Science:

• Biochemistry
• Organic Chemistry
• Cell Biology

Background:

• The scientific study of acids dates back to the 16th and 17th centuries.
• An acid is defined as a molecule releasing a hydrogen ion (H+) in aqueous solution.
• Key ionizable functional groups include carboxyl, phosphoryl, and amine groups.

Purpose of the Study:

• To provide a historical and evidence-based account of organic acids.
• To explain why cells do not produce metabolites that are acids using biochemical and organic chemistry evidence.

Main Methods:

• Review of historical definitions and scientific literature on acids.
• Analysis of biochemical and organic chemistry principles governing acid-base properties.
• Examination of dissociation constants (Kd) and pKd values to determine ionization states.

Main Results:

• Cells utilize biochemical pathways that favor the production of non-acidic or neutralized metabolites.
• The ionization state of acidic molecules is dependent on the solution's pH and the molecule's pKd.
• Lactic acid (HLa) has a pKd of 3.67, indicating significant ionization at physiological pH.

Conclusions:

• Cells maintain internal pH homeostasis by avoiding the production of acidic metabolites.
• Understanding acid-base chemistry is crucial for comprehending cellular metabolism and function.
• The principles of acid dissociation and pH determine the form (ionized or non-ionized) of molecules within a cell.