SDSU Effect of Ketone Bodies on Renal Ammoniagenesis Lab Report

Below I have reproduced a paper published September, 1971 by Guy Lemieux, Patrick Vinay, Pierre Robitaille, Gérard E. Plante, Yolande Lussier and Pierre Martin of the Renal Laboratory, Hôtel-Dieu Hospital and the Department of Medicine, University of Montreal School of Medicine, Montreal, Quebec, Canada

I have numberedcomponent sentences of the paper 1-8 to facilitate your finding the sections on which I require you to answercertain questions below , as you pretendthat you had done these experiments yourself, and are bringing your vast knowledge of Biochemistry of ketone bodies and renal ammoniogenesisto bear on this problem.

## Infusion of ketone bodies to ammonium chloride-loaded acidotic dogs was found to induce significant reduction in urin#ary excretion of ammonia. This effect could not be attributed to urinary pH variations. (1) 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. (2) . 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. (3). Administration of equimolar quantities of sodium acetoacetate adjusted to pH 6.0 resulted in a 50% decrease in renal ammonia production. (4) 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. (5)

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. (6) 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. (7) 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. (8)

Questions

1.A List the ketone bodies.

1.B Explain why would ammonium chloride-loaded dogs be acidotic?

1.C Would this be a respiratory or metabolic acidosis? Why?

1.DWhy do you think that infusion of ketone bodies to these dogs induced significant reduction in urinary excretion of ammonia, not attributed to urinary pH variations.

2A β-hydroxybutyric acid is a ketone body. Explain with suitable equations, how it is formed in the body and under what conditions.

2.B Define ketonemia, and nameat least three conditions that you might expect to see it in humans.

2.C Why did ketonemia occur in the experiment in your opinion.

3. Why do you think that 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?

4.A What is acetoacetate? 4.B Why do you think that the adding of sodium acetoacetate resulted in a 50% decrease in renal ammonia production?

5 A Why do you think that infusion of ketone bodies adjusted is usually accompanied by a small increase in extracellular bicarbonate, but infusion of sodium lactate or sodium bicarbonate in amounts sufficient to induce a similar rise in plasma bicarbonate results in only a slight decrement in ammonia production (15%)?

5.B. What is mannitol? How is it used in medicine? Why do you think that continuous infusion of 5% mannitol alone failed to influence renal ammoniogenesis.

6. Why do you think that infusion of pure sodium-free β-hydroxybutyric acid prepared resulted in a 50% decrease in renal ammoniogenesis in spite of the fact that both urinary pH and plasma bicarbonate fell significantly.

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

7.B Why do you think that infusion ofβ-hydroxybutyrate into the left renal artery resulted in a rapid decrease in ammoniogenesis by the perfused kidney.

8. 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.