OXIDATION OF SHORT AND MEDIUM-CHAIN C-2-C-8 FATTY-ACIDS IN SPRAGUE-DAWLEY RAT COLONOCYTES

Background-The predominant colonic short chain fatty acids, acetate, p ropionate, and butyrate, are oxidised into CO2 in colonocytes from rat and humans in the preferred order of butyrate (C-4) > propionate (C-3 ) > acetate (C-2) - hence butyrate is considered to be the principal o xidative substrate for colonocytes. Aims-To compare colonocyte oxidati on of valerate (C-5), hexanoate (C-6), and octanoate (C-8) with that o f butyrate. Methods-Isolated rat colonocytes were incubated in the pre sence of a concentration range of 1-C-14 labelled C-2-C-8 fatty acids. Oxidation rates were obtained by quantifying the production of (CO2)- C-14, and V-max, (maximum velocity) and K-m (Michaelis-Menten constant ) were calculated by computer fitting of the data to a Michaelis-Mente n plot. Results-The K-m value of acetate (0 . 56 (SEM 0 . 02) mmol/l) was about fourfold higher than the K-m of butyrate (0 . 13 (0 . 01) mm ol/l), whereas the K-m values of valerate (0 . 19 (0 . 01) mmol/l), he xanoate (0 . 19 (0 . 01) mmol/l), and octanoate (0 . 16 (0 . 01) mmol/ l) were of the same order of magnitude as the K-m of butyrate. Acetate did not influence butyrate oxidation, whereas butyrate strongly inhib ited the oxidation of acetate. By contrast, valerate, hexanoate, and o ctanoate inhibited colonocyte oxidation of butyrate equally or more th an the reverse inhibitory effect of butyrate on valerate, hexanoate, a nd octanoate oxidation. The maximum rates of ATP production were in th e order of valerate > octanoate = hexanoate > butyrate > acetate (28 . 47 (0 . 70), 21 . 78 (0 . 75), 21 . 33 (0 . 78), 16 . 12 (0 . 49), 9 . 09 (0 . 34) (mu mol/min/g) respectively). Conclusions-Valerate, hexa noate, and octanoate seem to be excellent substrates for colonocyte ox idation, similar to butyrate. These results may influence the choice o f fatty acid composition in enemas used for treatment of patients in w hom deficient colonocyte oxidation is suspected - for example, patient s with ulcerative colitis and diversion colitis.