Question

Please answer the following regarding this short read below:

1. Why do you think that the renal glutamine arteriovenous difference was abolished where ketones were infused?

2. Explain how ketone bodies depress renal ammoniogenesis by preventing the transformation of glutamine and glutamate into α-ketoglutarate in the mitochondria of the renal tubular cell.

Excerpt:

Infusion of ketone bodies to ammonium chloride-loaded acidotic dogs was found to induce significant reduction in urinary excretion of ammonia. This effect could not be attributed to urinary pH variations. Total ammonia production by the left kidney was measured in 25 animals infused during 90 min with the sodium salt of D,L-β-hydroxybutyric acid adjusted to pH 6.0 or 4.2. Ketonemia averaged 4.5 mM/liter. In all experiments the ammonia content of both urine and renal venous blood fell markedly so that ammoniogenesis was depressed by 60% or more within 60 min after the onset of infusion. Administration of equimolar quantities of sodium acetoacetate adjusted to pH 6.0 resulted in a 50% decrease in renal ammonia production. Infusion of ketone bodies adjusted to pH 6.0 is usually accompanied by a small increase in extracellular bicarbonate (3.7 mM/liter). However infusion of D,L-sodium lactate or sodium bicarbonate in amounts sufficient to induce a similar rise in plasma bicarbonate resulted in only a slight decrement in ammonia production (15%). The continuous infusion of 5% mannitol alone during 90-150 min failed to influence renal ammoniogenesis.

Infusion of pure sodium-free β-hydroxybutyric acid prepared by ion exchange (pH 2.2) resulted in a 50% decrease in renal ammoniogenesis in spite of the fact that both urinary pH and plasma bicarbonate fell significantly. During all experiments where ketones were infused, the renal extraction of glutamine became negligible as the renal glutamine arteriovenous difference was abolished. Renal hemodynamics did not vary significantly. Infusion of β-hydroxybutyrate into the left renal artery resulted in a rapid decrease in ammoniogenesis by the perfused kidney. The present study indicates that ketone bodies exert their inhibitory influence within the renal tubular cell. Since their effect is independent of urinary or systemic acid-base changes, it is suggested that they depress renal ammoniogenesis by preventing the transformation of glutamine and glutamate into α-ketoglutarate in the mitochondria of the renal tubular cell.

Answer 1

Ans1) The renal glutamine arteriovenous difference was abolished due to ketone infusion as it led to reduction in the ammonia excretion through urine. As the ketone was infused, it reduced the ammonia content of urine as well as the renal venous blood by 60% and this lead to abolishing of the renal glutamine arteriovenous. With the extraction of the glutamine becoming negligible and without the much variation of the renal hemodynamic and change in the pH, there was abolishing of renal glutamine arteriovenous difference.

Ans 2) The ketone bodies is responsible for depressing the renal ammoniogenesis and does so by preventing glutamate and glutamine transformation into α-ketogluturate. As the infusion of the ketone body increase, it reduces the renal ammoniogenesis where there is increase in the release and production of glutamate from glutamine, reduce uptake of glutamate and reduction in the process of gluconeogenesis. It is found that the suppression of the glutamate dehydrogenase that is an important metabolism for glutamine leads to depression of the renal ammoniogenesis. Also it is found that when there is increase in the infusion of the free beta hydroxybutyric acid, it reduces the process of renal ammoniogenesis by 50%. It is due to the ketone bodies that inhibit the action of the renal tubular cells and hence it all cumulatively leads to depressing the renal ammoniogenesis.