Metabolic fate of lactate, acetate, citrate and gluconate



The conjugate base of acetic acid, acetate is mated to a sodium cation instead of hydrogen. If one were to speak like a real scientist one might say that sodium acetate is the sodium salt of acetic acid. Cheap junk food manufacturers occasionally use it in lieu of actual salt and vinegar.



The conjugate base of lactic acid, lactate is present in Hartmann’s as a sodium salt. It is found in all kinds of unlikely places.  It is a food additive and apparently when given intravenously it can be used to treat an overdose of Class 1 antiarrhytmics like procainamide and quinidine



Citric acid salts of sodium come in three flavours: monosodium, disodium and trisodium. As can be plainly seen, there are three positions for sodium to occupy on the citrate anion. The monosodium variety is used to chelate calcium in packed cells to prevent clotting. The disodium species is an acidity-regulating food additive. Trisodium citrate is the hideous-tasting antacid shot you give to pregnant women as a premedication for their elective caesarian.



The sodium salt of gluconic acid. It is contributed to solutions as a mean of equalizing the cation-anion balance; however as an anion it seems to be physiologically useless, and it has only a theoretical role to play as a "bicarbonate precursor". It is mentioned here because each litre bag of Plasma-Lyte 148 contains 23 mmol of this stuff.

The metabolic fate of bicarbonate precursors

metabolic fate of infused bicarbonate precursors

It is very hard to find any medical information about the gluconate anion, try as you might. I managed to get a hold of this document, which makes several assertions about gluconate (for instance, that it is a normal metabolic product of glucose metabolism, and that the average human produces 25-30 grams of it per day).

According to this industrial chemistry paper, gluconate is not metabolised particularly well, and about 85% of it is excreted unchanged in the urine.

Do physiologists agree?  Perhaps. Why is everything about this subject written in the 1950s? There was passion then; people used to really fall in love with physiology. Not like this cynical age we live in now. The only real study on gluconate metabolism I could find was a report by Marjorie and DeWitt Stetten, written in 1953. The Stettens administering their radiolabelled sodium gluconate to a number of anaesthetized rats. They also concluded that the majority of the gluconate (something like 57%) was renally excreted in an unchanged form. 14% of the administered C14-labelled gluconate was excreted rapidly as carbon dioxide,and great portion of the C14 isotope was also renally excreted – as glucose. The rat livers also were aglow with C14 radioactivity, presumably because they were bloated with radiolabelled glycogen. This supports the assertion that gluconate is converted to glucose, and incorporated into energy stores.

The same authors investigated this pathway, and concluded that the first carbon (C1) of gluconate ends up turning into CO2, whereas the rest end up being converted to glucose, god knows how. The enzyme which may be responsible is glucose 1-dehydrogenase. A Swede named Brink found it in his puree of beef liver, and speculated regarding its function (again, in 1953). However, nothing further came of this.

So, if you can shed some light on this process, please contact me and I will send you a token gift, likely a T-shirt emblazoned with the pathway you explained.

In the meantime, my confusion is demonstrated in my allusion to a supernatural power as a catalytic influence on the conversion of gluconate to glucose.

Anyway; the other steps are fairly straightforward.

All these bicarbonate precursors funnel into the Citric Acid Cycle, which consumes hydrogen ions. The consumption of hydrogen ions is equivalent to the generation of bicarbonate (given the equilibrium between the two).

This conversion is 1:1 (i.e. one molecule of lactate consumes one proton and is therefore equivalent to one molecule of bicarbonate). There is some evidence that this is true in vivo. Among the precursors, it looks like acetate is the better choice because it is metabolised in most tissues, whereas 70% of the lactate needs a working liver.  

References, as always;

The articles linked to above are probably available in full text from whichever institution you have access to. If not, here is the bibliography so you can find the paper copies.

STETTEN MR, STETTEN D Jr. The metabolism of gluconic acid. J Biol Chem. 1950 Nov;187(1):241-52.

STETTEN MR, TOPPER YJ. Pathways from gluconic acid to glucose in vivo. J Biol Chem. 1953 Aug;203(2):653-64.

Brink N. G. (1953) Beef liver glucose dehydrogenase I. Purification and properties. Acta Chem. Scand. 7, 1081-1089.

H. E. Eliahou, P. H. Feng, U. Weinberg, A. Iaina, and E. Reisin Acetate and Bicarbonate in the Correction of Uraemic Acidosis.Br Med J. 1970 November 14; 4(5732): 399–401.

Necmiye Hadimioglu, , Iman Saadawy, , Tayyup Saglam, , Zeki Ertug, and Ayhan Dinckan, The Effect of Different Crystalloid Solutions on Acid-Base Balance and Early Kidney Function After Kidney Transplantation A & A July 2008 vol. 107no. 1 264-269

Barrie Phypers, FRCA and JM Tom Pierce, MRCP FRCA Lactate physiology in health and disease Contin Educ Anaesth Crit Care Pain (2006) 6 (3): 128-132

Mycielska, Maria E., et al. "Citrate transport and metabolism in mammalian cells." Bioessays 31.1 (2009): 10-20.