The unique role of the kidney in gluconeogenesis in the chicken. The significance of a cytosolic form of phosphoenolpyruvate carboxykinase.

The role of mitochondrial phosphoenolpyruvate carboxykinase in both hepatic and renal gluconeogenesis was studied in the chicken since this species reportedly lacks the cytosolic enzyme. Lactate is the major substrate used for glucose synthesis in isolated chicken hepatocytes but pyruvate, glycerol, and some amino acids, as well as lactate, are converted to glucose in isolated chicken kidney tubules. Renal gluconeogenesis and lactate production from pyruvate can be stimulated by ethanol. Amino acids also support a net production of ammonia by kidney tubules. Gluconeogenesis from all substrates and lactate production from pyruvate were stimulated by starvation (48 h), while ammoniagenesis was increased only from alanine. Ammonium chloride acidosis (7 days) had no effect on lactate or pyruvate metabolism but did increase the production of both glucose and ammonia from amino acids. These results are explained, in part, by differences in the intracellular distribution of phosphoenolpyruvate carboxykinase in the liver and kidney of the chicken. The predominantly mitochondrial (>99%) location of the liver enzyme results in an inability to provide cytosolic reducing equivalents required for gluconeogenesis. However, a significant portion of the renal enzyme is found in the cytosol (21% in fed birds; 40-50% in starved or acidotic birds). The presence of a distinct cytosolic enzyme in kidney but not liver has been confirmed immunochemically. It is proposed that, in the chicken, the liver (mitochondrial phosphoenolpyruvate carboxykinase) fuactions in gluconeogenesis to recycle lactate carbon (Cori cycle), while the kidney (cytosolic phosphoenolpyruvate carboxykinase) is the major organ for net gluconeogenesis from substrates such as amino acids.