scholarly journals Gluconeogenesis in the kidney cortex. Flow of malate between compartments

1970 ◽  
Vol 116 (3) ◽  
pp. 493-502 ◽  
Author(s):  
R. Rognstad
Keyword(s):  
Dehydrogenase Activity ◽  
Malate Dehydrogenase ◽  
Paper Chromatography ◽  
Analytical Methods ◽  
Specific Radioactivity ◽  
Kidney Cortex ◽  
Cortex Slices ◽  
Glucose Formation ◽  
Kidney Cortex Slices

1. Kidney-cortex slices from starved rats were incubated with l-[U-14C]lactate or l-[U-14C]malate plus unlabelled acetate and the specific radioactivity of the glucose formed was determined. In parallel experiments the specific radioactivity of the glucose formed from [1-14C]acetate plus unlabelled l-lactate and l-malate was determined. 2. By analytical methods the major products formed from the substrates were measured. The glucose formed was purified by paper chromatography for determination of specific radioactivity. 3. The specific radioactivity of the glucose formed from l-[U-14C]lactate agrees with predictions of a model based on interaction of the gluconeogenic and the oxidative pathways. 4. The specific radioactivity of the glucose formed from l-[U-14C]malate agrees with the predicted value if rapid malate exchange between the cytosol and mitochondria is assumed. 5. The rate of malate exchange between compartments was estimated to be rapid and at least several times the rate of glucose formation. 6. The specific radioactivity of the glucose formed from [1-14C]acetate plus unlabelled l-lactate or l-malate agrees with the predictions from the model, again assuming rapid malate exchange between compartments. 7. Malate exchange between compartments together with reversible malate dehydrogenase activity in the mitochondria and cytosol also tends to equilibrate isotopically the NADH pool in these compartments. 3H from compounds such as l-[2-3H]lactate, which form NAD3H in the cytosol, appears in part in water; and 3H from dl-β-hydroxy[3-3H]butyrate, which forms NAD3H in the mitochondria, appears in part in glucose, largely on C-4.

The Effect of Nicotinic Acid, 5-Methylpyrazole-3-carboxylic Acid (U-19425), and Dibutyryl Cyclic AMP on Renal Gluconeogenesis

1971 ◽  
Vol 49 (2) ◽  
pp. 102-105
Author(s):  
Andrew Issekutz
Keyword(s):  
Carboxylic Acid ◽  
Cyclic Amp ◽  
Nicotinic Acid ◽  
Kidney Cortex ◽  
Dibutyryl Cyclic Amp ◽  
Renal Gluconeogenesis ◽  
Minimal Concentration ◽  
Cortex Slices ◽  
Glucose Formation ◽  
Kidney Cortex Slices

The effects of nicotinic acid, 5-methylpyrazole-3-carboxylic acid (U-19425), and dibutyryl (DB-) cyclic AMP on gluconeogenesis from lactate, oxalacetate, and glycerol were studied in kidney cortex slices. DB-cyclic AMP stimulated glucose formation from lactate (+67%), but not from oxalacetate or glycerol. Nicotinic acid and U-19425 inhibited gluconeogenesis from all three substrates by 30–63%. DB-cyclic AMP stimulated gluconeogenesis from lactate in the presence of either inhibitor. DB-cyclic AMP abolished the inhibition by either drug on glucose formation from oxalacetate or glycerol. It is concluded that nicotinic acid and U-19425 may inhibit gluconeogenesis by decreasing the cyclic AMP level within the cells, and that a minimal concentration of cyclic AMP may be functional above the triose phosphate level.

scholarly journals Gluconeogenesis in the kidney cortex. Effects of d-malate and amino-oxyacetate

1970 ◽  
Vol 116 (3) ◽  
pp. 483-491 ◽  
Author(s):  
R. Rognstad ◽  
J. Katz
Keyword(s):  
Malate Dehydrogenase ◽  
High Speed ◽  
Tricarboxylic Acid Cycle ◽  
Rat Kidney ◽  
Supernatant Fraction ◽  
Kidney Cortex ◽  
Rat Kidney Cortex ◽  
High Concentrations ◽  
Cortex Slices ◽  
Kidney Cortex Slices

1. Rat kidney-cortex slices incubated with d-malate alone formed very little glucose. d-Malate, however, augmented gluconeogenesis from l-lactate and inhibited gluconeogenesis from pyruvate and l-malate. 2. d-Malate had little effect on the rate of the tricarboxylic acid cycle with or without other substrates added. 3. d-Malate inhibited the activity of the l-malate dehydrogenase in a high-speed-supernatant fraction from kidney cortex. 4. It was concluded that d-malate inhibited either the operation of the cytoplasmic l-malate dehydrogenase or malate outflow from the mitochondria in the intact kidney-cortex cell. This supports the hypothesis of Lardy, Paetkau & Walter (1965) and Krebs, Gascoyne & Notton (1967) on the role of malate as carrier for carbon and reducing equivalents in gluconeogenesis. 5. Gluconeogenesis from l-lactate in kidney-cortex slices was strongly inhibited by a low concentration (0.1mm) of amino-oxyacetate, whereas glucose formation from pyruvate, malate, aspartate and several other compounds was only slightly affected. 6. High concentrations of l-aspartate largely reversed the inhibition of gluconeogenesis from l-lactate caused by amino-oxyacetate. 7. Amino-oxyacetate inhibited strongly the glutamate–oxaloacetate transaminase in the 30000g supernatant fraction of a kidney-cortex homogenate. The presence of l-aspartate decreased the inhibition of the transaminase by amino-oxyacetate. 8. Detritiation of l-[2-3H]aspartate was inhibited by 90% during an incubation of kidney-cortex slices with l-lactate and amino-oxyacetate. 9. Low concentrations (10μm) of artificial electron acceptors such as Methylene Blue and phenazine methosulphate abolished most of the inhibition of gluconeogenesis from l-lactate by amino-oxyacetate. This is interpreted as an activation of net malate outflow from the mitochondria by-passing the inhibited transfer of oxaloacetate. 10. These findings support the concept that transamination to aspartate is involved in the transfer of oxaloacetate from mitochondria to cytosol required in gluconeogenesis from l-lactate.

scholarly journals The interrelationship of the concentration of hydrogen ions, bicarbonate ions, carbon dioxide and calcium ions in the regulation of renal gluconeogenesis in the rat

1973 ◽  
Vol 136 (3) ◽  
pp. 445-453 ◽  
Author(s):  
George A. O. Alleyne ◽  
Hernando Flores ◽  
Anne Roobol
Keyword(s):  
Phosphoenolpyruvate Carboxylase ◽  
Rat Kidney ◽  
Respiratory Acidosis ◽  
Kidney Cortex ◽  
Rat Kidney Cortex ◽  
Bicarbonate Ions ◽  
Cortex Slices ◽  
Glucose Formation ◽  
Kidney Cortex Slices

1. The interrelationship of acidosis and Ca2+on the stimulation of gluconeogenesis by rat kidney-cortex slices was studied. 2. Ca2+stimulated gluconeogenesis from glutamine, glutamate, 2-oxoglutarate, succinate, malate, pyruvate, lactate and fructose, but not from galactose. 3. The [Ca2+] needed for optimum gluconeogenesis was about 2mm, but at this concentration, acidosis, produced in vitro by a decrease of [HCO3−] in the medium at constant pCO2 or by an increase in pCO2 at constant [HCO3−], did not stimulate gluconeogenesis. 4. In the absence of Ca2+, acidosis (low [HCO3−]) stimulated gluconeogenesis from glutamine, glutamate, 2-oxoglutarate, succinate, malate, pyruvate and lactate but not from fructose or galactose. With succinate as substrate, the stimulatory effect of acidosis (low [HCO3−]) disappeared at Ca2+concentrations above 1.0mm. 5. The [HCO3−] was the most important determinant of the acidosis effect since a decrease of pH caused by an increase in pCO2 did not uniformly stimulate gluconeogenesis, whereas a decrease in [HCO3−] without a change in pH consistently stimulated glucose formation in a way similar to the stimulation produced by acidosis (low [HCO3−]) in the absence of Ca2+. 6. Acidosis in vitro inhibited the rate of decrease of activity of phosphoenolpyruvate carboxylase in slices, and Ca2+caused an increase in the activity of fructose 1-phosphate aldolase. 7. Respiratory acidosis in vitro caused an increase in the activity of phosphoenolpyruvate carboxylase in kidney cortex and an increase in gluconeogenesis from glutamine. 8. Possible points of interaction between Ca2+, H+and HCO3−with the gluconeogenic sequence are discussed.

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