The Computational Acid–Base Chemistry of Hepatic Ketoacidosis

Opposing evidence exists for the source of hydrogen ions (H+) during ketoacidosis. Organic and computational chemistry using dissociation constants alpha equations all pertinent ionizable metabolites were used to (1) document atomic changes in chemical reactions ketogenesis ketolysis (2) identify sources quantify added fractional (~) H+ exchange (~H+e). All computations performed pH conditions spanning from 6.0 7.6. Summation ~H+e given substrates products each reaction resulted net pathway coefficients, where negative revealed ~H+ release positive uptake. Results that liver (pH = 7.0), ending acetoacetate (AcAc), β-hydroxybutyrate (β-HB), acetone −0.9990, 0.0026, 0.0000, respectively. During ketogenesis, was only evident HMG CoA production, which is caused by hydrolysis not dissociation. Nevertheless, there a though this diminishes with greater proportionality production. For muscle 7.1) brain 7.2), coefficients β-HB AcAc oxidation −0.9649 0.0363 (muscle), −0.9719 0.0291 (brain), The larger values result covalent oxidation–reduction. combined ketolysis, would be metabolic condition vivo, coefficient depends once again on final ketone body product. production liver, transference blood, ratio 0.6:0.2:0.2 β-HB:AcAc:acetone, blood transfer, total (ketosis) equate −0.1983, −0.0003, −0.2872, −0.4858, traditional theory bodies being acids causing systemic acidosis incorrect. yield differ depending though, general, small ketosis. Products formed (HMG-CoA, acetoacetate, β-hydroxybutyrate) are created as negatively charged bases, acids, body, acetone, does have pH-dependent groups. Proton or uptake predominantly modification, acid dissociation/association. Ketosis (ketogenesis ketolysis) results release. extent dependent between β-hydroxybutyrate, acetone.