scholarly journals The relationship between glutamate deamination and gluconeogenesis in kidney

1983 ◽  
Vol 210 (3) ◽  
pp. 695-698 ◽  
Author(s):  
R T Bogusky ◽  
L M Lowenstein ◽  
T T Aoki
Keyword(s):  
Glutamate Dehydrogenase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fold Increase ◽  
Purine Nucleotide ◽  
Single Intraperitoneal Injection ◽  
Purine Nucleotide Cycle ◽  
Kidney Perfusion ◽  
Nh3 Formation ◽  
The Relationship ◽  
Glucose Formation

The effect of 3-mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase [GTP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32], was tested on NH3 formation via the purine nucleotide cycle and glutamate dehydrogenase (EC 1.4.1.2). NH3 excretion in rats increased 70-fold after 48 h of NH4Cl feeding, from 12.2 +/- 4.5 to 862 +/- 190 mumol/mg of creatinine. At 4 h after a single intraperitoneal injection of 3-mercaptopicolinate into NH4Cl-fed rats, NH3 excretion was inhibited by 93%. Kidneys of NH4Cl-fed plus 3-mercaptopicolinate-treated rats, compared with those of NH4Cl-fed rats, showed a 3.5-fold increase in the content of IMP, 5-fold increase in adenylosuccinate, 4-fold increase in aspartate, and a 30% increase in AMP. 3-Mercaptopicolinate completely inhibited NH3 and glucose formation from glutamate in tubules from acidotic rats and NH3 formation from aspartate in kidney perfusion experiments. When transamination in tubules was prevented by 2-amino-4-methoxy-trans-but-3-enoic acid, formation of glucose, but not of NH3, from glutamate was inhibited. 3-Mercaptopicolinate completely inhibited NH3 formation from aspartate in the presence of the aminotransferase inhibitor in kidney tubules. The data show that NH3 can be formed via glutamate dehydrogenase and the purine nucleotide cycle at significant and approximately equal rates. 3-Mercaptopicolinate has no direct effect on NH3 formation via glutamate dehydrogenase, but inhibits that via the purine nucleotide cycle. We conclude that gluconeogenesis is not regulatory for NH3 formation in kidney.

scholarly journals Sources of ammonia for mammalian urea synthesis

1978 ◽  
Vol 176 (3) ◽  
pp. 733-737 ◽  
Author(s):  
H A Krebs ◽  
R Hems ◽  
P Lund ◽  
D Halliday ◽  
W W Read
Keyword(s):  
Glutamate Dehydrogenase ◽  
Initial Rate ◽  
Adenine Nucleotides ◽  
Rat Hepatocytes ◽  
The Other ◽  
Amino Group ◽  
Urea Synthesis ◽  
Purine Nucleotide ◽  
Carbamoyl Phosphate ◽  
Purine Nucleotide Cycle

The initial rate of incorporation of [15N]alanine into the 6-amino group of the adenine nucleotides in rat hepatocytes was about one-eighteenth of the rate of incorporation into urea. Thus the purine nucleotide cycle cannot provide most of the ammonia needed in urea synthesis for the carbamoyl phosphate synthase reaction (EC 2.7.2.5). On the other hand, contrary to the view expressed by McGivan & Chappell [(1975) FEBS Lett. 52, 1–7], the experiments support the view that hepatic glutamate dehydrogenase can supply the required ammonia.

scholarly journals Changes in the activity of rat muscle AMP deaminase in relation to the proportion of dietary protein

1974 ◽  
Vol 32 (3) ◽  
pp. 539-548 ◽  
Author(s):  
L. V. Turner ◽  
E. B. Fern
Keyword(s):  
Amino Acid ◽  
Glutamate Dehydrogenase ◽  
Dietary Protein ◽  
Metabolizable Energy ◽  
Amp Deaminase ◽  
Purine Nucleotide ◽  
Alternative Scheme ◽  
Protein Energy ◽  
Purine Nucleotide Cycle ◽  
Nutritional Studies

1. The purine nucleotide cycle has been proposed (Lowenstein, 1972) as an alternative scheme for amino acid deamination in tissues, such as skeletal muscle, having low concentrations of glutamate dehydrogenase (EC 1.4.1.2).2. Activities of AMP deaminase (EC 3.5.4.6), one of the enzymes of the cycle, have been measured in soleus, plantaris and extensor digitorum longus muscles of rats maintained for 18 d on diets providing 0, 0·035 or 0·10 net dietary protein energy (energy supplied by utilizable protein: total metabolizable energy, NDp:E), and in rats given the 0·10 NDp:E diet for 3 d after the 0 or 0·035 NDp:E regimens.3. Concentration of AMP deaminase in the different muscles from the control (0·10 NDp:E diet) rats appeared to bear an inverse relationship to the proportion of mitochondria-rich fibres (i.e. rich in glutamate dehydrogenase) in each muscle.4. Dietary protein deprivation (0 or 0·035 NDp:E) led to adaptive reductions in AMP-deaminase activity in the soleus and plantaris muscles, but in the extensor muscle the 0·035 NDp:E diet produced no change, while the 0 NDp:E diet caused an increase in activity.5. Refeeding the 0·10 NDp:E diet to the protein-deprived rats caused reductions of AMP-deaminase activity to lower levels in all three muscles, except in the instance of soleus in rats refed after the 0·035 NPp:E diet.6. In view of the different responses shown by the three muscles to the dietary treatments, the importance of specifying the particular muscles used in future nutritional studies is emphasized.7. The adaptive changes in AMP deaminase are discussed in terms of operation of the purine nucleotide cycle for amino acid deamination responding to the changes in amino acid catabolism known to be caused in muscle by these protein-deficient diets.

scholarly journals Importance of glutamate dehydrogenase stimulation for glucose and glutamine synthesis in rabbit renal tubules incubated with various amino acids.

1998 ◽  
Vol 45 (3) ◽  
pp. 825-831
Author(s):  
K Winiarska ◽  
P Bozko ◽  
T Lietz ◽  
J Bryła
Keyword(s):  
Glutamate Dehydrogenase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Lactate Production ◽  
Renal Tubules ◽  
Glycerol Utilization ◽  
Key Enzyme ◽  
Glutamine Synthesis ◽  
Glutamate Synthesis ◽  
Glucose Formation ◽  
Stimulation Of

The effect of 2-aminobicyclo[2.2.1]heptan-2-carboxylic acid (BCH), an L-leucine nonmetabolizable analogue and an allosteric activator of glutamate dehydrogenase, on glucose and glutamine synthesis was studied in rabbit renal tubules incubated with alanine, aspartate or proline in the presence of glycerol and octanoate, i.e. under conditions of efficient glucose formation. With alanine+glycerol+octanoate the addition of BCH resulted in a stimulation of alanine and glycerol consumption, accompanied by an increased glucose, lactate and glutamine synthesis. In contrast, when alanine was substituted by either aspartate or proline, BCH altered neither glucose formation nor glutamine and glutamate synthesis, while an accelerated glycerol utilization was accompanied by a small increase in lactate production. In view of the BCH-induced changes in intracellular metabolite levels the acceleration of gluconeogenesis by BCH in the presence of alanine+glycerol+octanoate is probably due to (i) increased uptake of alanine via alanine aminotransferase, (ii) stimulation of phosphoenolpyruvate carboxykinase, a key-enzyme of gluconeogenesis, (iii) rise of glucose-6-phosphatase activity, as well as (iv) activation of the malate-aspartate shuttle resulting in an augmented glycerol utilization for lactate and glucose synthesis.

scholarly journals The purine nucleotide cycle in the regulation of ammoniagenesis during induction and cessation of chronic acidosis in the rat kidney

1981 ◽  
Vol 196 (1) ◽  
pp. 323-326 ◽  
Author(s):  
R T Bogusky ◽  
K A Steele ◽  
L M Lowenstein
Keyword(s):  
Glutamate Dehydrogenase ◽  
Rat Kidney ◽  
Recovery Period ◽  
Purine Nucleotide ◽  
Sprague Dawley ◽  
Metabolic Intermediates ◽  
Control Value ◽  
Sprague Dawley Rats ◽  
Purine Nucleotide Cycle ◽  
Subsequent Withdrawal

The effect of chronic acid feeding and its subsequent withdrawal was determined on the amounts of the metabolic intermediates and enzymic activities of the purine nucleotide cycle. Sprague-Dawley rats were given 1.5% (w/v) NH4Cl in their drinking water for 5 days. The renal excretion of NH3 rose 70-fold and the rats developed acidosis. The amount of renal IMP rose from a control value of 4.5 +/- 2.2 to 20.4 +/- 3.7nmol/g of kidney after 48h of acid feeding (P less than 0.001) and fell to normal within 48h of the recovery. Adenylosuccinate concentrations fell from a control value of 4.5 +/- 0.9nmol/g of kidney to 1.2 +/- 0.3nmol/g (P less than 0.005) by day 5 of acidosis and continued to fall to undetectable values by 48h after recovery. The amount of AMP remained constant through the acid-feeding and the recovery periods. The activity of adenylosuccinate synthetase, the rate-limiting enzyme of the purine nucleotide cycle, paralleled the rise and fall in NH3 excretion. The activities of phosphate-dependent glutaminase and glutamate dehydrogenase were elevated during the acid-feeding and the recovery period. Thus changes in the purine nucleotide cycle correlate with changes in NH3 excretion to a more parallel degree than does the activity of glutaminase or glutamate dehydrogenase.

Relationship among gluconeogenesis, QO2, and Na+ transport in the perfused rat kidney

1982 ◽  
Vol 242 (5) ◽  
pp. F508-F513
Author(s):  
P. Silva ◽  
R. Hallac ◽  
K. Spokes ◽  
F. H. Epstein
Keyword(s):  
Oxygen Consumption ◽  
Sodium Transport ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Perfusion Pressure ◽  
Rat Kidney ◽  
Albumin Concentration ◽  
Na Transport ◽  
Perfused Rat Kidney ◽  
The Relationship ◽  
Glucose Formation

The relationship among sodium transport (TNa), oxygen consumption (QO2), and gluconeogenesis was studied in isolated perfused rat kidneys in which glucose formation was enhanced by providing pyruvate as a substrate and by prior treatment with methylprednisolone. TNa was increased abruptly by increasing perfusion pressure as to increase GFR or by lowering the albumin concentration of a hyperoncotic perfusate as to allow glomerular filtration to occur. Increases in TNa of 40% were accompanied by little or no increase in QO2, whereas gluconeogenesis decreased 55-80%. Conversely, a decrease in perfusion pressure that lowered TNa produced an increase in glucose formation without a change in QO2. When gluconeogenesis was blocked with 0.15 mM 3-mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase, QO2 increased together with TNa as perfusion pressure was raised. The results suggest that the energy needed for ion transport by the kidney may under some circumstances be borrowed from nontransport functions and, therefore, that basal oxygen consumption may vary with the rate of reabsorptive transport.

Contribution of purine nucleotide cycle to intranephron ammoniagenesis in rats

1988 ◽  
Vol 255 (6) ◽  
pp. F1122-F1127
Author(s):  
K. Tamura ◽  
H. Endou
Keyword(s):  
Amino Acids ◽  
Metabolic Acidosis ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Specific Inhibitor ◽  
Ammonia Production ◽  
Purine Nucleotide ◽  
Nephron Segments ◽  
A Value ◽  
Purine Nucleotide Cycle ◽  
High Concentrations

To evaluate the contribution of the purine nucleotide cycle (PNC) in renal ammoniagenesis, ammonia production (AP) in cortical tubular suspensions and microdissected nephron segments of control and acidotic rats was determined using various amino acids, including glutamine (Gln) and aspartate (Asp). In the cortical tubular suspensions, the best substrate for ammoniagenesis was Gln (153.1 +/- 19.4 nmol.mg protein-1.15 min-1) followed by Asp (70.9 +/- 11.4). Metabolic acidosis resulted in a significant increase of AP only from Gln (316.5 +/- 36.1 nmol.mg protein-1.15 min-1, P less than 0.01 vs. control). Intranephron distribution of AP (pmol/mm or a glomerulus/15 min) from Gln showed that the first segment of the proximal tubule (S1) was highest in control (95.7 +/- 9.0), and its AP markedly increased in acidosis (221.6 +/- 8.3, P less than 0.001 vs. control). The most interesting and striking finding was that with Asp as a substrate, AP was maximal in S1 (165.0 +/- 32.8), with a value exceeding that from Gln. An adenylosuccinase inhibitor, 6-mercaptopurine (0.1 mM), significantly inhibited AP from Asp in S1 and S3, and from Gln in S1. On the contrary, a specific inhibitor of phosphoenolpyruvate carboxykinase, 3-mercaptopicolinate (0.1 mM), caused a significant decrease of AP from Gln, but not from Asp, in S1. From these results it could be concluded that AP via PNC can occur at high rates, especially in S1, only when Asp is present at high concentrations.

scholarly journals Retinoic acid-induced modulation of rat liver transglutaminase and total polyamines in vivo

1988 ◽  
Vol 253 (1) ◽  
pp. 33-38 ◽  
Author(s):  
M Piacentini ◽  
L Fesus ◽  
C Sartori ◽  
M P Ceru
Keyword(s):  
Retinoic Acid ◽  
Acid Treatment ◽  
Actinomycin D ◽  
Tissue Transglutaminase ◽  
Fold Increase ◽  
Retinoic Acid Treatment ◽  
Single Intraperitoneal Injection ◽  
The Relationship ◽  
Transglutaminase 3

The effect of a single intraperitoneal injection of retinoic acid on liver transglutaminase (EC 2.3.2.13) activity and total putrescine, spermidine and spermine was studied. The results demonstrate that: (1) transglutaminase activity is increased over control values as early as 4-6 h after treatment, reaching a maximum (2-fold increase) at 12 h and returning to control values at 36 h; (2) the retinoic acid-induced form of enzyme is the soluble tissue transglutaminase; (3) actinomycin D treatment does not completely inhibit the early (6 h) increase of activity, while suppressing that at 12 h; (4) the immunoassay of the soluble transglutaminase shows that, 6 h after treatment, there is no increase in the protein, whereas at 12 and 24 h a significant increase is observed; (5) putrescine, but not spermidine and spermine, increases (5-7-fold) 6 and 18 h after the retinoic acid treatment. The possibility also that the expression of soluble transglutaminase is modulated in vivo by retinoic acid and the relationship to polyamine levels are discussed.

Monitoring Anticoagulant Therapy by Activated Partial Thromboplastin Time: Hirudin Assessment

1994 ◽  
Vol 72 (05) ◽  
pp. 685-692 ◽  
Author(s):  
Michael T Nurmohamed ◽  
René J Berckmans ◽  
Willy M Morriën-Salomons ◽  
Fenny Berends ◽  
Daan W Hommes ◽  
...  
Keyword(s):  
Whole Blood ◽  
Partial Thromboplastin Time ◽  
Ex Vivo ◽  
Fold Increase ◽  
Heparin Therapy ◽  
Activated Partial Thromboplastin Time ◽  
Recombinant Hirudin ◽  
Interindividual Differences ◽  
The Relationship

SummaryBackground. Recombinant hirudin (RH) is a new anticoagulant for prophylaxis and treatment of venous and arterial thrombosis. To which extent the activated partial thromboplastin time (APTT) is suitable for monitoring of RH has not been properly evaluated. Recently, a capillary whole blood device was developed for bed-side monitoring of the APTT and it was demonstrated that this device was suitable to monitor heparin therapy. However, monitoring of RH was not evaluated.Study Objectives. To evaluate in vitro and ex vivo the responsiveness and reproducibility for hirudin monitoring of the whole blood monitor and of plasma APTT assays, which were performed with several reagents and two conventional coagulometers.Results. Large interindividual differences in hirudin responsiveness were noted in both the in vitro and the ex vivo experiments. The relationship between the APTT, expressed as clotting time or ratio of initial and prolonged APTT, and the hirudin concentration was nonlinear. A 1.5-fold increase of the clotting times was obtained at 150-200 ng/ml plasma. However, only a 2-fold increase was obtained at hirudin levels varying from 300 ng to more than 750 ng RH/ml plasma regardless of the assays. The relationship linearized upon logarithmic conversion of the ratio and the hirudin concentration. Disregarding the interindividual differences, and presuming full linearity of the relationship, all combinations were equally responsive to hirudin.Conclusions. All assays were equally responsive to hirudin. Levels up to 300 ng/ml plasma can be reliably estimated with each assay. The manual device may be preferable in situations where rapid availability of test results is necessary.

scholarly journals The Relationship Between the Home Environment and Falls for Older Adults With Visual Impairments

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 770-770
Author(s):  
Bonnielin Swenor ◽  
Aleksandra Mihailovic ◽  
Pradeep Ramulu
Keyword(s):  
Older Adults ◽  
Home Environment ◽  
Visually Impaired ◽  
Visual Impairments ◽  
Fold Increase ◽  
Engineering Society ◽  
Environment Assessment ◽  
Risk Factors For Falls ◽  
The Relationship

Abstract The home environment and features of the home have been identified as important risk factors for falls, and may pose particular risk for older adults with visual impairments given difficulty with hazard perception. We used data from 245 participants in the Falls in Glaucoma Study [mean age: 71 years, mean follow-up: 31 months] with homes graded using our previously validated Home Environment Assessment for the Visually Impaired (HEAVI), which quantifies the number of in-home fall-related hazards and found that neither the number of hazards nor the percentage of hazardous items were associated falls/year. However, each 10-fold increase in lighting was associated with a 35% lower rate of falls/year (RR=0.65, 95%CI=0.46 to 0.92) and there was a 50% reduction in falls/year when lighting was at or above 30 footcandles (minimum lighting level recommended by the Engineering Society of North America) compared to lighting <30 footcandles (RR=0.50, 95%CI=0.26 to 0.96).

scholarly journals The Purine Nucleotide Cycle

1972 ◽  
Vol 247 (1) ◽  
pp. 162-169 ◽  
Author(s):  
Keith Tornheim ◽  
John M. Lowenstein
Keyword(s):  
Purine Nucleotide ◽  
Purine Nucleotide Cycle
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