[Babcock_Hall]

Diabetic ketoacidosis is seen in type I and occasionally type II diabetes, and it is a serious complication.  The slowing down of the Krebs' cycle causes the acetyl CoA produced in the β-oxidation of fatty acylthioesters to be shunted toward the production of ketone bodies, acetone, acetoacetate and hydroxybutyrate.  What I am trying to understand is the reason for the acidosis.  The biochemistry textbooks I have consulted so far mention that two of these compounds are acids (when written as neutral molecules).  However in the presentations of the pathways I have looked at, the reactions are not always correctly balanced, if I am not mistaken.  One possibility is that the production of ketone bodies is not the source of the acid, but rather it is the β-oxidation.  One equation I have seen indicates that for the 16-carbon saturated fatty acyl thioester palmitoyl CoA, there are 7 protons produced, along with 8 molecules of acetyl CoA.  I am attaching a pdf file of the pathway.  In this drawing I modified a textbook presentation to include protons at reactions 2 and 4. 

[Babcock_Hall]

“Anion gap = [Na+] – ([Cl-] + [HCO3-])

“The normal value is about 12 meq/liter (range 8 to 16).  The anion gap estimates the unmeasured anions in the plasma and is normally composed of polyanionic plasma proteins such as albumin (1 g/dL of serum protein possesses negative charge equivalent to 1.7 to 2.4 meq/liter), phosphate, sulfate, lactate, and other organic anions.

“The anion gap is particularly useful in evaluating metabolic acidosis.  Elevated values indicate that the acidosis is due to ingestion or generation of a fixed acid, stronger than H2CO3, at rates that exceed the rate at which the anion can be excreted from the body.  Examples are diabetic ketoacidosis, in which acetoacetic and -hydroxybutyric acids are generated; lactic acidosis; and renal failure, in which the rate of generation of strong acids is normal but the anions the acids, e.g., phosphate and sulfate, cannot be normally excreted.  Ingestion of methanol, which generates formic acid, ingestion of ethylene glycol, which yields oxalic acid, and salicylate intoxication all produce high anion gap acidosis.”

p. 188 in Principles of Biochemistry: Mammalian Biochemistry, 7th ed., Smith E, Hill, RL, Lehman IR, Lefkowitz, RJ, Handler P, White A, McGraw-Hill, 1983.