HDCN Article Review/Hyperlink

Halperin ML, Kamel KS

D-lactic acidosis: Turning sugar into acids in the gastrointestinal tract

Kidney Int (Jan) 49:1-8 1996

D-lactic acidosis is an uncommon but biochemically fascinating disease process. It is seen almost exclusively in patients following jejunoileal bypass or small bowel resections (and in ruminants), often following the use of antibiotics or a large meal of simple sugars. Halperin and Kamel's review focuses on the specific metabolic pathways and stoichiometry involved in the production and metabolism of various organic acids such as acetic, butyric, propionic and especially L- and D-lactic acids. As these organic acids are produced even in healthy individuals, the normal metabolism of these acids is reviewed. Focus is given to the normal production of butyrate by colonic bacteria and the utilization of this organic acid by the colonic mucosa as a required metabolite.

Normally only minute amounts of D-lactate are produced endogenously. The abnormal intestinal anatomy in these patients causes undigested sugars to be delivered distally and bacteria to migrate proximally, allowing prolonged contact between the two with consequent fermentation. When overproduction and absorption of D-lactate occurs, metabolic acidosis may be produced associated with an elevation in the anion gap, unless urinary excretion of the D-lactate anion occurs faster than the depleted bicarbonate can be regenerated. In the past it was thought that the limited ability of the enzyme D-2-hydroxyacid dehydrogenase to metabolize D-lactate was an important pathegenic factor in its accumulation. More recent data suggest that D-lactate is metabolized at a significant rate, though only about 1/5th as rapidly as L-lactate (the latter is metabolized by the stereospecific enzyme L-lactate dehydrogenase. Therefore, it is likely that in patients predisposed to developing D-lactic acidosis, it is the marked overproduction of D-lactate rather than limited metabolism which leads to the syndrome of dizziness, confusion and other typical neurological symptoms.

D-lactate is metabolized in humans to pyruvate which may be metabolized to acetate and then to ATP via oxidative phosphorylation. Free fatty acids exist in serum in inverse proportion to insulin, and compete with pyruvate as substrate for oxidative phosphorylation. Because of this, the authors speculate, though without substantiating evidence, that insulin administration to patients with D-lactate would decrease free fatty acid levels, promoting metabolism of D-lactate.

Comment: This excellent analysis of D-lactic acidosis emphasizes the biochemistry of intestinal production of organic acids by bacteria and the elimination of D-lactate by metabolism and urinary excretion. Other observers have noted that thiamine deficiency inhibits pyruvate metabolism and causes D-lactate accumulation. Alternative means of D-lactate production exist: D-lactate can be produced from ketones in cats (and presumably humans) with diabetes and during the metabolism of propylene glycol in patients with an overdose of this hydrocarbon. The clinical aspects of this disease received little attention, so we must still ponder whether the neurologic symptoms seen during exacerbations of D-lactic acidosis are due to the accumulation of D-lactate or perhaps to the coproduction of other noxious organic acids. (Greg Cowell, M.D, Chicago, IL)

This may be the only stereo-isomer related disease. It is of interest that Arthur C. Clarke wrote a short story/novelette some years ago that utilized a different stereo-isomer condition to track down a criminal. If anyone remembers the particulars of that story, I like to hear from them. As someone who did JI Bypasses from 1964 to about 1989, I can remember agonizing over the neurological symptoms reported intermittently by patients. I kept trying to relate these to some avitaminosis or similar deficiency, until the publication of the seminal paper by Dr. Oh and associates, in 1979.
Sidney F Kahn, MD (sidkahn@webtv.net)
La Mirada, Calif - Saturday, May 19, 2001 at 08:39:06 (PDT)