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Biomedical subjects

P D Gollnick

Publications and source records attributed to P D Gollnick.

At least 19 recordsLinked to original sources
PubMed2006

Aspartic acid 214 in Citrobacter freundii tyrosine phenol-lyase ensures sufficient C--H-acidity of the external aldimine intermediate and proper orientation of the cofactor at the active site.

In the X-ray structure of tyrosine phenol-lyase (TPL) Asp214 is located at H-bonding distance from the N1 atom of the cofactor. This residue has been replaced with Ala and Asn and the properties of the mutant enzymes have been studied. The substitutions result in a decrease in the cofactor affinity of about four orders of magnitude. D214A and D214N TPLs do not catalyze the decomposition of l-Tyr and 3-fluoro-l-Tyr. They decompose substrates, containing better leaving groups with rates reduced by one or two orders of magnitude. Lognormal resolution of the spectra of the mutant enzymes revealed that the N1 atom of the cofactor is deprotonated. Spectral characteristics of internal and external aldimines of the mutant TPLs and the data on their interaction with quasisubstrates demonstrate that replacements of Asp214 lead to alteration of active site conformations. The mutant enzymes do not form noticeable amounts of a quinonoid upon interaction with inhibitors, but catalyze isotope exchange of C-alpha-proton of a number of amino acids for deuterium in (2)H(2)O. The k(ex) values for the isotope exchange of l-phenylalanine and 3-fluoro-l-tyrosine are close to the k(cat) values for reacting substrates. Thus, for the mutant TPLs the stage of C-alpha-proton abstraction may be considered as a rate-limiting for the whole reaction.

Alanine↗
PubMed2003

Role of arginine 226 in the mechanism of tryptophan indole-lyase from Proteus vulgaris.

In the spatial structure of tryptophanase from Proteus vulgaris the guanidinium group of arginine 226 forms a salt bridge with the 3;-oxygen atom of the coenzyme. The replacement of arginine 226 with alanine using site-directed mutagenesis reduced the affinity of the coenzyme for the protein by one order of magnitude compared to the wild-type enzyme. The catalytic activity of the mutant enzyme in the reaction with L-tryptophan was reduced 10(5)-fold compared to the wild-type enzyme. The rates of the reactions with some other substrates decreased 10(3)-10(4)-fold. The mutant enzyme catalyzed exchange of the C-alpha-proton in complexes with some inhibitors with rates reduced 10(2)-fold compared to the wild-type enzyme. Absorption and circular dichroism spectra of the mutant enzyme and the enzyme-inhibitor complexes demonstrate that the replacement of arginine 226 with alanine does not significantly affect the tautomeric equilibrium of the internal aldimine, but it leads to an alteration of the optimal conformation of the coenzyme-substrate intermediates.

Amino Acid Sequence↗
PubMed2000

Light-associated and processing-dependent protein binding to 5' regions of rbcL mRNA in the chloroplasts of a C4 plant.

In amaranth, a C(4) dicotyledonous plant, the plastid rbcL gene (encoding the large subunit of ribulose-1,5-bisphosphate carboxylase) is regulated post-transcriptionally during many developmental processes, including light-mediated development. To identify post-transcriptional regulators of rbcL expression, three types of analyses (polysome heel printing, gel retardation, and UV cross-linking) were utilized. These approaches revealed that multiple proteins interact with 5' regions of rbcL mRNA in light-grown, but not etiolated, amaranth plants. Light-associated binding of a 47-kDa protein (p47), observed by UV cross-linking, was highly specific for the rbcL 5' RNA. Binding of p47 occurred only with RNAs corresponding to mature processed rbcL transcripts (5'-untranslated region (UTR) terminating at -66); transcripts with longer 5'-UTRs did not associate with p47 in vitro. Variations in the length of the rbcL 5'-UTR were found to occur in vivo, and these different 5' termini may prevent or enhance light-associated p47 binding, possibly affecting rbcL expression as well. p47 binding correlates with light-dependent rbcL polysome association of the fully processed transcripts in photosynthetic leaves and cotyledons but not with cell-specific rbcL mRNA accumulation in bundle sheath and mesophyll chloroplasts.

5' Untranslated Regions↗
PubMed2000

Citrobacter freundii tyrosine phenol-lyase: the role of asparagine 185 in modulating enzyme function through stabilization of a quinonoid intermediate.

Asn185 is an invariant residue in all known sequences of TPL and of closely related tryptophanase and it may be aligned with the Asn194 in aspartate aminotransferase. According to X-ray data, in the holoenzyme and in the Michaelis complex Asn185 does not interact with the cofactor pyridoxal 5'-phosphate, but in the external aldimine a conformational change occurs which is accompanied by formation of a hydrogen bond between Asn185 and the oxygen atom in position 3 of the cofactor. The substitution of Asn185 in TPL by alanine results in a mutant N185A TPL of moderate residual activity (2%) with respect to adequate substrates, L-tyrosine and 3-fluoro-L-tyrosine. The affinities of the mutant enzyme for various amino acid substrates and inhibitors, studied by both steady-state and rapid kinetic techniques, were lower than for the wild-type TPL. This effect mainly results from destabilization of the quinonoid intermediate, and it is therefore concluded that the hydrogen bond between Asn185 and the oxygen at the C-3 position of the cofactor is maintained in the quinonoid intermediate. The relative destabilization of the quinonoid intermediate and external aldimine leads to the formation of large amounts of gem-diamine in reactions of N185A TPL with 3-fluoro-L-tyrosine and L-phenylalanine. For the reaction with 3-fluoro-L-tyrosine it was first possible to determine kinetic parameters of gem-diamine formation by the stopped-flow method. For the reactions of N185A TPL with substrates bearing good leaving groups the observed values of k(cat) could be accounted for by taking into consideration two effects: the decrease in the quinonoid content under steady-state conditions and the increase in the quinonoid reactivity in a beta-elimination reaction. Both effects are due to destabilization of the quinonoid and they counterbalance each other. Multiple kinetic isotope effect studies on the reactions of N185A TPL with suitable substrates, L-tyrosine and 3-fluoro-L-tyrosine, show that the principal mechanism of catalysis, suggested previously for the wild-type enzyme, does not change. In the framework of this mechanism the observed considerable decrease in k(cat) values for reactions of N185A TPL with L-tyrosine and 3-fluoro-L-tyrosine may be ascribed to participation of Asn185 in additional stabilization of the keto quinonoid intermediate.

Alanine↗
PubMed1998

Effect of creatine phosphate on the contractile activity in acutely failing rat heart.

The hypothesis was tested that infusion of a solution containing creatine phosphate (CP) into rats with acutely failing hearts would enhance recovery of cardiac function. The acutely failing heart was produced by constricting the ascending aorta. This overload produced failure in approximately 25 min. At the point of failure the constriction was removed and solutions containing sterile physiological saline (PSS), PSS and CP, PSS and creatine, or PSS and creatine plus phosphate were infused. Cardiac function was assessed from systolic and diastolic blood pressure, +/- dp/dt, heart rate, and cardiac work. Ca2+ uptake by isolated sarcoplasmic reticulum and the concentrations of selected blood and tissue metabolites were measured. Normal cardiac function was restored in the PSS-CP infused rats whereas all other treatments did not restore cardiac function. Adenosine triphosphate and CP had declined in the myocardium of the failing hearts while lactate was elevated. The concentrations of these metabolites were normal in the PSS-CP infused animals. The glycogen concentration in the myocardium was reduced following the constriction. Ca2+ uptake by isolated sarcoplasmic reticulum was depressed in the failed hearts but normal in the hearts of CP-infused animals. These results demonstrate that the infusion of CP into animals with failing hearts can be effective in restoring cardiac function.

Animals↗
PubMed1995

Human fiber size and enzymatic properties after 5 and 11 days of spaceflight.

Biopsies from the vastus lateralis muscle were obtained from three astronauts before and after two 5-day flights and from five astronauts before and after one 11-day flight (space shuttle flights: STS-32, -33, and -34). Muscle fibers from two separate samples from each biopsy were classified as type I and II or as type I, IIA, and IIB by using qualitative myofibrillar adenosinetriphosphatase (ATPase) staining. Cross-sectional area (CSA), number of capillaries per fiber, and the activities of succinate dehydrogenase (SDH), alpha-glycerophosphate dehydrogenase (GPD), and myofibrillar ATPase were determined from one sample of fibers of each myofibrillar ATPase type. Postflight biopsies had 6-8% fewer type I fibers than preflight. Mean fiber CSAs were 16-36% smaller after the 11-day flight with the relative effect being type IIB > IIA > I. Mean fiber CSAs were 11 and 24% smaller in type I and II fibers after 5 days of flight. Myofibrillar ATPase activities increased in type II but not in type I fibers after flight, whereas SDH activity was unaffected in either fast or slow fibers. GPD activity in type I fibers was approximately 80% higher (P > 0.05) postflight compared with preflight. Myofibrillar ATPase/SDH ratios in type II fibers were higher after than before flight, suggesting that some fast fibers were more susceptible to fatigue after flight. The GPD/SDH ratios were elevated in some type I fibers after spaceflight. The number of capillaries per fiber was 24% lower after than before flight, whereas the number of capillaries per unit CSA of muscle tissue was unchanged. These data suggest that adaptations in the size, metabolic properties, and vascularity of muscle fibers can occur rapidly in the space environment. These adaptations were qualitatively similar to those observed in animals after actual or simulated spaceflight conditions for short periods.

Adenosine Triphosphatases↗
PubMed1995

Myosin heavy chain isoforms of human muscle after short-term spaceflight.

The influence of microgravity on the myosin phenotype of skeletal muscle fibers in the vastus lateralis of eight crew members was studied before and after 5-day (n = 3) and 11-day (n = 5) spaceflights (space shuttle flights: STS-32, -33 and -34). Single-fiber electrophoresis analyses showed that the proportion of fibers expressing only slow (type I) myosin heavy chain (MHC) in the vastus lateralis was significantly lower after than before 11 days of spaceflight. Although the family of type II MHC isoforms was elevated post- compared with preflight, the distribution among the isoforms of type II MHC was not statistically different. Based on monoclonal and polyclonal antibodies specific for three adult MHC isoforms and single-fiber electrophoresis, approximately 3% of the fibers analyzed coexpressed all three adult MHC isoforms. The results from immunohistochemical staining with two different sets of antibodies indicate a reduction in the percentage of fibers expressing type I MHC as a result of spaceflight. The mean difference, however, was significant only when the fibers were categorized simply as type I or II. These changes appeared to be highly individualized among the astronauts. These results suggest that a rapid change in MHC isoform expression can occur in some muscle fibers after a relatively brief exposure to spaceflight.

Adult↗
PubMed1994

Effect of exercise on hexokinase distribution and mitochondrial respiration in skeletal muscle.

Horses were subjected to treadmill running at 65% (submaximal) or 100% (maximal) VO2,max to examine the effects of exercise on subcellular distribution of hexokinase (HK) and on mitochondrial respiration. It is hypothesized that the fraction of HK bound to mitochondria will be reduced due to an elevation of glucose-6-phosphate (G-6-P) concentration in the exercising muscle and that such release of HK from mitochondria will depress oxidative phosphorylation. Changes in muscle G-6-P concentration, pH, subcellular HK distribution, mitochondrial respiration and other metabolites were determined in biopsy samples pre-exercise, immediately post-exercise and during the recovery phase. The fraction of HK associated with mitochondria decreased from 38% to 7% at the end of maximal exercise; exercise at VO2,max also reduced respiratory capacity of muscle homogenates by 20% and was associated with a fivefold increase in muscle [G-6-P], a potent agent known to dissociate HK from mitochondria. The HK distribution returned to normal within 60 min after exercise and the reassociation of the HK with mitochondria parallelled the removal of muscle G-6-P. No changes in muscle HK distribution and respiration were found following the submaximal exercise despite the fact that G-6-P was slightly elevated. Muscle concentrations of adenosine triphosphate, creatine phosphate and glycogen and pH dropped after exercise while lactate concentration increased. The amount of mitochondria-bound HK was also altered in vitro in a preparation of mitochondria isolated from rat skeletal muscle to examine the effect of the bound HK on mitochondrial respiration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

Dissipation of metabolic heat in the horse during exercise.

Horses were exercised at 40, 65, and 90% of their maximum O2 uptake (VO2max) until moderately fatigued (approximately 38, 15, and 9 min, respectively) to assess heat loss through different routes. Approximately 4,232, 3,195, and 2,333 kcal of heat were generated in response to exercise at these intensities. Of this, approximately 7, 16, and 20% remained as stored heat 30 min postexercise. Respiratory heat loss, estimated from the temperature difference between blood in the pulmonary and carotid arteries and the cardiac output, was estimated to be 30, 19, and 23% of the heat produced during exercise at the three intensities. The kinetics of the increases in muscle and blood temperature were similar, with the greatest change in temperature occurring in muscle (+3.8, 5.2, and 6.1 degrees C after exercise at 40, 65, and 90% of VO2max, respectively). The temperature of blood in the superficial thoracic vein was approximately 2 degrees C below that of arterial blood at rest. This difference had increased to approximately 3 degrees C during the last minute of exercise. The rate of sweating at sites on the back and neck increased with exercise intensity to a common peak of approximately 40 ml.m-2.min-1. If complete evaporation had occurred, water loss in response to exercise (estimated to be 12, 10, and 7.7 liters for the different intensities of exercise) greatly surpassed that required for dissipation of the metabolic heat load.

Animals↗
PubMed1993

Equine plasma and blood volumes decrease with dehydration but subsequently increase with exercise.

The effects of dehydration and 40 min of exercise at approximately 40% of maximal O2 consumption on plasma volume (PV) and blood volume (BV) were studied in six horses. Horses were exercised while euhydrated (C); 4 h after administration of furosemide (1.0 mg/kg i.v.; FDH), which induced isotonic dehydration; and after 30 h without water (DDH), which caused hypertonic dehydration. Dehydration resulted in decreases of 6.3 and 9.9% for PV and BV, respectively, with FDH and 10.7 and 8.5%, respectively, with DDH. During exercise in C, PV and BV increased by 12.7 and 20.0%, respectively; during exercise with FDH, they increased by 11.7 and 26.1%, respectively; and during exercise with DDH, PV decreased by 1.3% from predehydration values, while BV increased by 18.7%. Hematocrit and total plasma protein concentration rose to higher values throughout exercise in FDH and DDH than in C; plasma [Na+] was higher in DDH than in FDH and C, [Cl-] was higher in DDH and lower in FDH than in C, and [K+] was lower in FDH and DDH than in C through exercise and recovery. From these results, we conclude that increases in PV and BV are normal features of low-intensity exercise in the horse. The increases in BV not only augment O2 carriage but also help maintain circulating volume. These increases can be modified by preexercise dehydration, the nature of which affects the extent of modification.

Animals↗
PubMed1993

Effects of dehydration on thermoregulatory responses of horses during low-intensity exercise.

Effects of dehydration on thermoregulatory and metabolic responses were studied in six horses during 40 min of exercise eliciting approximately 40% of maximal O2 consumption and for 30 min after exercise. Horses were exercised while euhydrated (C), 4 h after administration of furosemide (FDH; 1.0 mg/kg i.v.) to induce isotonic dehydration, and after 30 h without water (DDH) to induce hypertonic dehydration. Cardiac output was significantly lower in FDH (144.1 +/- 8.0 l/min) and in DDH (156.6 +/- 6.9 l/min) than in C (173.1 +/- 6.2 l/min) after 30 min of exercise. When DDH, FDH, and C values were compared, dehydration resulted in higher temperatures in the middle gluteal muscle (41.9 +/- 0.3, 41.1 +/- 0.2, and 40.6 +/- 0.2 degrees C, respectively) and pulmonary artery (40.8 +/- 0.3, 40.1 +/- 0.2, and 39.7 +/- 0.2 degrees C, respectively). Temperatures in the superficial thoracic vein and subcutaneous sites on the neck and back and peak sweating rates on the neck and back were not significantly different in DDH and C. In view of higher core temperatures during exercise after dehydration and decrease in cardiac output without concomitant increases in peripheral temperatures or reduced sweating rates, we conclude that the impairment of thermoregulation was primarily due to decreased transfer of heat from core to periphery.

Animals↗
PubMed1991

Substrates for muscle glycogen synthesis in recovery from intense exercise in man.

1. Intramuscular glyconeogenesis from lactate after intense exercise was examined by using the one-legged knee extension model which enables evaluation of metabolism in a well-defined muscle group. 2. In seven subjects measurements of leg blood flow and arterial-venous differences of various substrates were performed in individuals after intense, exhaustive knee extensor exercise lasting 3.0 min. Muscle glycogen and lactate concentrations were determined in the quadriceps muscle immediately after exercise and three times during 1 h of recovery. 3. Muscle glycogen increased from 93.7 +/- 6.7 (+/- S.E.M.) to 108.8 +/- 8.1 mmol (kg wet wt)-1 during the recovery period. Muscle lactate was 27.1 +/- 2.1 mmol (kg wet wt)-1 at the end of exercise and decreased to 14.5 +/- 2.1, 6.7 +/- 1.1, and 3.0 +/- 0.5 mmol (kg wet wt)-1 after 3, 10 and 60 min of recovery, respectively. 4. More than two-thirds of the lactate that accumulated in the muscle during the intense exercise was released into the blood. It was estimated that between 13 and 27% of the lactate could have been converted to glycogen. This corresponded to a glycogen resynthesis rate from lactate of 0.17-0.34 and 0.002 mmol glucosyl units min-1 (kg wet wt)-1 for the first 10 and last 50 min of recovery, respectively. 5. The O2 debt of the leg was 1.5 l of which the resynthesis of ATP, creatine phosphate (CP) and glycogen and reloading of haemoglobin (Hb) and myoglobin (Mb) only could account for one-third. It is proposed that the elevated oxygen uptake during recovery is linked to the metabolic use of intramuscular triacylglycerol.

Adult↗
PubMed1990

Respiratory and metabolic responses in the horse during moderate and heavy exercise.

Thoroughbred horses were exercised to fatigue on a treadmill at 62% and 100% of their VO2max. Hypoxemia occurred at the onset of exercise under both exercise conditions. This hypoxemia persisted to fatigue during the heavy exercise but progressively diminished as the exercise continued and had disappeared by the end of exercise at the lighter load. As a result of the hypoxemia the oxygen content of arterial blood during exercise at VO2max was 17% below its carrying capacity. However, under both experimental conditions the CaO2 still exceeded that of rest owing to an elevation in hemoglobin concentration. The temperature of blood at the point of fatigue was similar, 41.0 +/- 0.2 degrees C and 41.1 +/- 0.2 degrees C, for exercise at 62% and 100% VO2max, respectively. Muscle samples collected at rest and at the termination of exercise did not demonstrate major differences between the exercise conditions except for a higher [lactate] and lower pH following the heavy exercise. From these results it can be suggested that the combined effects of an elevated body temperature, changes in muscle pH, and oxygen delivery may all be factors contributing to limit exercise capacity in the horse.

Adenosine Triphosphate↗
PubMed1990

The effect of high-intensity exercise on the respiratory capacity of skeletal muscle.

The effect of high-intensity exercise on the respiratory capacity of skeletal muscle was studied in horses which ran five 600-m bouts on a track with 2 min of rest between exercise bouts, or once to fatigue on a treadmill at an intensity that elicited the maximal oxygen uptake. Venous blood and biopsy samples of the middle gluteal muscle were collected at rest, after each exercise bout, and 30 and 60 min post-exercise. Blood samples were analyzed for lactate concentration and pH and muscle samples for metabolites, pH, and respiratory capacity. Venous blood and muscle pH declined to 6.91 +/- 0.02 and 6.57 +/- 0.02, respectively, after the fifth track run and to 6.98 +/- 0.02 and 6.71 +/- 0.07, respectively, after treadmill running. Muscle metabolite changes were consistent with the metabolic response to high-intensity exercise. Muscle respiratory capacity declined greater than 20% (P less than 0.05) after a single exercise bout and was 45% of the control value after the fifth track run. Tissue respiration was depressed 60 min post-exercise but was normal 24 h later. These observations suggest that high-intensity exercise impairs the respiratory capacity of the working muscle. Although this occurred in parallel with reductions in pH, other factors could be responsible for this response.

Animals↗
PubMed1990

Kinetics of VO2 and VCO2 in the horse and comparison of five methods for determination of maximum oxygen uptake.

To determine whether maximum oxygen uptake (VO2max) in the horse in influenced by type of exercise test, five different protocols were evaluated in eight untrained Thoroughbreds exercised on a treadmill. With all protocols, horses were given a 5 min warm-up on a 10 per cent treadmill slope. Three protocols were at a 10 per cent slope and included: 1) increasing the running speed by 1 to 2 m/sec every 60 secs from 4 m/sec to a maximum of 12 m/sec; 2) running at 12 m/sec until fatigue; and 3) running for 3 to 4 mins at speeds ranging from 6 to 12 m/sec with rest pauses between exercise bouts. The fourth protocol employed a 24 per cent slope where animals exercised for 5 mins at 2 m/sec followed by 3 mins at 5 m/sec, and 2 mins at 6 m/sec. The fifth test involved running at 11 m/sec while the slope of the surface was increased every 2 mins until the horses could not maintain the pace. A plateau in VO2 occurred in all protocols except when exercise was performed on a 24 per cent slope. Slow speed exercise at a steep grade (24 per cent) produced the highest VO2 (P < 0.05) even though there was no plateau in the VO2. A steady state for VO2 and VCO2 existed 90 secs after the onset of exercise with all protocols which involved 2 mins or more at each speed. The VO2 and VCO2 values at all speeds of the rapid incremental exercise test were not different to those found at steady state in the third exercise protocol.

Animals↗
PubMed1990

Anaerobic energy production and O2 deficit-debt relationship during exhaustive exercise in humans.

1. Eight subjects performed one-legged, dynamic, knee-extensor exercise, first at 10 W followed by 10 min rest, then at an intense, exhaustive exercise load (65 W) lasting 3.2 min. After 60 min recovery, exercise was performed for 8-10 min each at 20, 30, 40 and 50 W. Measurements of pulmonary oxygen uptake, heart rate, blood pressure, leg blood flow, and femoral arterial-venous differences of oxygen content and lactate were performed as well as determination of ATP, creatine phosphate (CP) inosine monophosphate (IMP) and lactate concentrations on biopsy material from the quadriceps muscle before and immediately after the intense exercise, and at 3, 10 and 60 min into recovery. 2. Individual linear relations (r = 0.95-1.00) between the power outputs for submaximal exercise and oxygen uptakes (leg and pulmonary) were used to estimate the energy demand during intense exercise. Pulmonary and leg oxygen deficits determined as the difference between energy demand and oxygen uptake were 0.46 and 0.48 l (kg active muscle)-1, respectively. Limb and pulmonary oxygen debts (oxygen uptake during 60 min of recovery - pre-exercise oxygen uptake) were 0.55 and 1.65 l (kg active muscle)-1, respectively. 3. During the intense exercise, muscle [ATP] decreased by 30% and [CP] by 60% from resting concentrations of 6.2 and 22.4 mmol (kg wet wt)-1, respectively, and [IMP] increased to 1.1 mmol (kg wet wt)-1. Muscle [lactate] increased from 2 to 28.1 mmol (kg wet wt)-1, and the concomitant net lactate release was 14.8 mmol (kg wet wt)-1 or about 1/3 of the total net lactate production. During recovery 70% of the accumulated lactate was released to the blood, and the nucleotides and CP returned to about 40 and 85% of pre-exercise values at 3 and 10 min of recovery, respectively. 4. Total reduction in ATP and CP (and elevation of IMP) during the intense exercise amounted to 16.4 mmol ATP (kg wet wt)-1, which together with the lactate production accounted for 83.1 mmol ATP (kg wet wt)-1. In addition 6-8 mmol ATP (kg wet wt)-1 are made available related to accumulation of glycolytic intermediates including pyruvate (and alanine). Estimated leg oxygen deficit corresponded to an ATP production of 94.7 mmol ATP kg-1; this value included 3.1 mmol kg-1 related to unloading of HbO2 and MbO2.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Ammonia metabolism during intense dynamic exercise and recovery in humans.

This study examined the dynamics for ammonia (NH3) metabolism in human skeletal muscle during and after intense one-legged exercise. Subjects (n = 8) performed dynamic leg extensor exercise to exhaustion (3.2 min). Muscle NH3 release increased rapidly to a maximum of 314 +/- 42 mumol/min and declined immediately on cessation of exercise. Recovery was complete in approximately 20 min. Arterial [NH3] increased less rapidly and reached its maximum 2-3 min into recovery. These data demonstrate that NH3 clearance is more sensitive to the cessation of exercise than is NH3 release from skeletal muscle. Muscle [NH3] increased three to fourfold during exercise and represented 74 +/- 8% of the total net NH3 formation. Thus the change in muscle [NH3] alone underestimates the NH3 production. There was no evidence that the muscle-to-venous blood NH3 ratio shifts in accordance with the H+ data. Thus other factors must contribute to the NH3 release from active muscle. The total net NH3 formed corresponded with the intramuscular inosine 5'-monophosphate accumulation, suggesting that the NH3 was derived from AMP deamination. Changes in the known modulators of AMP deaminase (ATP, ADP, H+) were moderate, so the mechanisms initiating the deamination remain obscure.

Adenine Nucleotides↗