Sensitivity of ketogenesis and citric acid cycle to stevioside inhibition of palmitate transport across the cell membrane

The effect of stevioside, an inhibitor of long-chain fatty acid transport, on ketogenesis and on [14C]CO2 production from [1-14C] palmitate (100-300µM) was investigated in the isolated and hemoglobin-free perfused rat liver. Stevioside (2.5mM), a sweet glycoside found in Stevia rebaudiana leaves, inhibited both parameters, but had a lower effection on [14C]CO2 production. At 300µM palmitate and 150 µM albumin, for example, ketogenesis was inhibited by 66.3%, whereas no significant inhibition of [14C]CO2 was demonstrable. These results were interpreted to reflect 1) different degress of saturation of the citric acid cycle and the ketogenic patheay and 2) changes in the redox state of the mitochondrial NAD+-NADH couple which may also occur upon stevioside infusion

Saturated fatty acids with different chain length as ketogenic substrates in the rat liver

Production of ketone bodies, activation of oxygen uptake and production of [14C] carbon dioxide due to fatty acids of various chain lengths were measured in the isolated perfused rat liver. As ketogenic substrates, the fatty acids investigated can be ordered in the following sequence: strate < palmitate < laureate < decanoate < miristate < octanoate. For activation of oxygen consumptor, the same sequence is observed. A good linear correlation between the increase in oxygen uptake (deltaO2) and production of ketone bodies was found, with a mean deltaO2 of 0.66 mol per mol ketone bodies. This is a relatively low value when confronted with the known stoichiometry of ß-oxidation, and may be an indication of complexities in the metabolism of exogenously added fatty acids in the perfused liver

The influence of albumin on palmitate transport in the isolated perfused rat liver

Unidirectional fluxes (influx and efflux) and the net flux of palmitate across the hepatocyte membrane were measured in the intact rat liver employing the multiple indicator dilution technique. At albumin concentrations in the range between 0.1 and 0.5 mM the influx rate was 2.3 times greater than that of the net flux. The rate of efflux was somewhat higher than the net flux, indicating that palmitate undergoes an exchange process across the liver cell membranes with efflux to the extracellular albumin site being significant. At. lower albumin concentrations, hower, the influx/net flux approached unit, implying that transport becomes a rate-limiting factor for metabolism