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Department of Physiology, State University of New York Health Science Center, Syracuse, New York 13210
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ABSTRACT |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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We examined a
possible mechanism to account for the maintenance of peak AMP
deamination rate in fast-twitch muscle of rats fed the creatine analog
-guanidinopropionic acid (-GPA), in spite of reduced abundance of
the enzyme AMP deaminase (AMPD). AMPD enzymatic capacity (determined at
saturating AMP concentration) and AMPD protein abundance (Western blot)
were coordinately reduced ~80% in fast-twitch white gastrocnemius
muscle by -GPA feeding over 7 wk. Kinetic analysis of AMPD in the
soluble cell fraction demonstrated a single Michaelis-Menten constant
(Km; ~1.5 mM) in control muscle extracts. An additional high-affinity
Km (~0.03 mM)
was revealed at low AMP concentrations in extracts of -GPA-treated muscle. The kinetic alteration in AMPD reflects increased molecular activity at low AMP concentrations; this could account for high rates
of deamination in -GPA-treated muscle in situ, despite the loss of
AMPD enzyme protein. The elimination of this kinetic effect by
treatment of -GPA-treated muscle extracts with acid phosphatase in
vitro suggests that phosphorylation is involved in the kinetic control
of skeletal muscle AMPD in vivo.
muscle energetics; inosine monophosphate; adenine nucleotides; creatine analog; enzyme kinetics
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INTRODUCTION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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THE DECREASE IN phosphocreatine (PCr) that occurs
during intense contractions of fast-twitch muscle impairs the
ATP-buffering role of creatine kinase [CK; PCr + MgADP + H+ 
MgATP + creatine
(Cr)]. When PCr concentration is low, the removal of
AMPf 1
by AMP deaminase (AMPD; AMP 
IMP + NH3) draws the near-equilibrium adenylate kinase reaction (2ADP ATP + AMP) in the ATP synthesis direction, which buffers decreases in the
ATP-to-ADPf ratio. Feeding the Cr
analog -guanidinopropionic acid (-GPA) to rats results in
depletion of muscle Cr and PCr, with replacement by -GPA and -GPA
phosphate (-GPAP) (6, 7, 19, 23). Because -GPAP is a much poorer
substrate in the CK reaction than is PCr [2-fold higher
Michaelis-Menten constant
(Km),
1,000-fold lower maximal velocity
(Vmax)
(4)], there is essentially no rapid high-energy phosphate
transfer between -GPAP and ATP during contractions (11, 20). The
ATP-buffering function of the CK reaction is thereby impaired, even
though -GPAP concentration remains high (11, 20, 23).
Interestingly, several weeks of -GPA feeding induced an ~80%
decrease in fast-twitch muscle extract AMPD activity and protein abundance (13, 23). In spite of the apparent reduced AMPD enzymatic
capacity, however, IMP accumulation occurred earlier, and at a similar
peak rate compared with normal fast-twitch muscle, under identical
conditions of hindlimb muscle stimulation (23). At least two
possibilities could compensate for the lower content of AMPD to account
for sustained normal high rates of AMP deamination in -GPA-treated
muscle during contractions: a substrate effect and/or altered
enzyme kinetic behavior. Elevated substrate (AMP) concentration could
increase the reaction velocity (V)
of a fixed number of enzyme molecules by increasing the concentration
of the enzyme-substrate complex. It is possible that larger excursions of ADPf and
AMPf occur during contractions in
-GPA-treated muscle compared with controls due to loss of the CK
buffer system. In addition, -GPA treatment could cause an alteration
of the AMPD molecule itself, producing a kinetic effect that increases
the sensitivity of the enzyme to AMP (e.g., by lowering the
Km). This mechanism could compensate for the decreased AMPD abundance by increasing the effective molecular activity of AMPD during
physiological contraction conditions. This possibility is supported by
a report suggesting that phosphorylation of purified AMPD can lower its Km (22), albeit
the effect is small.
To investigate the hypothesis that a kinetic alteration of AMPD may
contribute to the observed AMP deamination behavior in -GPA-treated
fast-twitch muscle, we evaluated the enzyme kinetics of AMP deamination
and followed the time course of changes in muscle AMPD capacity and
80-kDa AMPD protein abundance in fast-twitch muscle from rats fed
-GPA over 7 wk.
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METHODS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Animal care.
Male Sprague-Dawley rats (Taconic Farms, Germantown, NY) weighing
250-300 g were housed three per cage in a temperature-controlled room (20-21°C) with a 12:12-h light-dark cycle. Control
animals were fed Purina lab chow, and experimental animals were fed the same diet containing 1% -GPA (wt/wt), which was synthesized as previously described (15). Both groups were provided with food and
water ad libitum. All procedures involving the use of animals were
approved by the State University of New York Health Science Center
Committee for the Humane Use of Animals and were in accordance with the
guidelines for the care and use of animals of the American Physiological Society.
Tissue sampling.
Muscle tissues were obtained from control rats and from rats fed
-GPA for 1, 2, 3, 5, and 7 wk, under pentobarbital sodium anesthesia
(5 mg/100 g body wt, ip). Muscles taken included the superficial
portion of the medial gastrocnemius (the white gastrocnemius; WG),
which is composed predominantly of fast-twitch white fibers (3). Muscle
sections were clamp-frozen in aluminum tongs that had been cooled in
liquid nitrogen and were stored at 
80°C until analysis.
Portions of the mixed gastrocnemius muscles from each animal were
weighed wet and dried at 85°C to a constant dry weight to determine
muscle water content.
AMPD capacity and kinetics. Portions of muscle sections were homogenized (1:9 or 1:19, wt/vol) in 100 mM KCl, 50 mM imidazole-HCl, and 10 mM reduced glutathione, pH 7.0, and the homogenates were centrifuged for 1 min at 13,000 g to separate soluble and particulate cell material. The supernatant (soluble cell fraction) was removed, spun again, and retained; there was no visible pellet from the second spin. The pellet of the initial spin (particulate cell fraction) was washed and resuspended in homogenization buffer.
A near-Vmax response was elicited for AMPD in both cell fractions using 15 mM AMP (pH 7.0 and 30°C); this is taken as the enzymatic capacity of AMPD (Table 1). Total muscle AMPD capacity was determined either by direct assay of the initial muscle homogenate or by the sum of the soluble and particulate AMPD capacities, determined separately. The two methods for obtaining total muscle AMPD capacity yielded results that were not systematically or significantly different (n = 20, P > 0.05).
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-GPA-treated WG (7-wk
animals) at a dose of 10 U/ml. These mixtures were incubated at room
temperature for 30 min, after which they were used for kinetic analysis
of AMPD as described above. Preliminary experiments demonstrated that
these conditions of dose and time were sufficient to elicit the maximal
acid phosphatase-induced response in AMPD kinetics.
AMPD Western blots.
Pieces (5-10 mg) of frozen WG muscles were pulverized under liquid
nitrogen and homogenized by hand in 19 volumes of extraction buffer
containing 10 mM
NaH2PO4,
1% sodium dodecyl sulfate (SDS), and 6 M urea, pH 7.4. This extract
was incubated for 3 h at 37°C, and an aliquot was used to determine
the protein content (bicinchoninic acid protein assay kit; Pierce).
-Mercaptoethanol was added to the remaining extract to a final
concentration of 1%. SDS-polyacrylamide gel electrophoresis (PAGE) was
performed using 10% polyacrylamide gels. A total of 6 µg total
muscle protein was loaded per sample lane. Prestained molecular mass
standards (low range, Bio-Rad) were included in each gel to determine
the apparent molecular masses of AMPD species. Proteins were
transferred to nitrocellulose membranes, and Western blot procedures
and densitometric analyses were performed as previously described (23).
The primary antibody was a previously characterized (10) polyclonal
antiserum raised in rabbit against purified rat skeletal muscle AMPD.
Aliquots of two particular muscle samples were included in each of the gels, to serve as internal standards for comparison of the stain density measurements across gels.
AMPD immunoprecipitations. Homogenates were prepared as described for AMPD enzyme assays. Twenty microliters of the soluble cell fraction were added to 5 µl of antibody solution [1 part of undiluted antiserum to 1 part of tris(hydroxymethyl)aminomethane (Tris)-buffered saline (TBS; 50 mM Tris, 27 mM NaCl, and 0.1% bovine serum albumin, pH 7.0)], and the mixture was incubated at room temperature for 1 h. Twenty-five microliters of Staphylococcus aureus PANSORBIN cells (Calbiochem-Behring, La Jolla, CA) prewashed in TBS buffer were added. The mixture was incubated at room temperature for 1 h and centrifuged (5 min at 13,000 g) to pellet the sorbent cells and attached antibody-AMPD conjugates. The supernatant was then assayed for AMPD capacity as described above. The conditions were optimized for maximal specific immunoprecipitation. Anti-skeletal muscle AMPD antibody was the same as that employed in Western blots. Immunoprecipitated AMPD capacity was calculated as the difference between the AMPD capacity remaining in the supernatant of contemporaneous samples with and without antibody.
Calculations and statistics. To determine Km, kinetic data were plotted as double-reciprocal plots (1/V vs. 1/S, where S is substrate concentration) and as normalized double-reciprocal plots (1/%V15 mM vs. 1/S) in which V values were expressed as a percent of the V elicited at 15 mM AMP (Vmax; see Fig. 2). The Km estimations were verified by plotting the data in an Eadie-Hofstee (V/S vs. V) format.
Depending on the nature of the comparison, either one-way analysis of variance followed by Tukey's procedure or the unpaired t-test was used to determine significant differences (P < 0.05). Where significant differences exist, P values are indicated. The AMPD activity data are expressed per gram of wet muscle mass, since neither the total water content nor the total protein content of gastrocnemius muscle was altered by-GPA feeding.
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RESULTS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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AMPD capacity.
As anticipated from previous studies (13, 23), the total WG AMPD
capacity measured in vitro was decreased by -GPA feeding to ~20%
of control values at 7 wk (Table 1). The rate and extent of decline in
AMPD capacity during -GPA treatment were both greater in the soluble
than in the particulate cell fraction. Solely as a result of the
continuing decline in soluble AMPD capacity, the total AMPD capacity
continued to decline between 5 and 7 wk (Table 1).
AMPD Western blots.
The predominant species of AMPD protein in control WG muscle migrates
in SDS-PAGE at ~80 kDa (Fig. 1, Table
2). An additional, much less
abundant species occurs at ~60 kDa, and a further species at ~56
kDa is detectable at very low levels in some control muscles. The
abundance of 80-kDa AMPD protein in WG decreased progressively with
time during -GPA treatment to ~15-20% of control levels at 7 wk (Fig. 1, Table 2). Increases in the abundance of the 60- and 56-kDa
forms also occurred with -GPA feeding, but these did not appear to
be stoichiometric to the decreases in the 80-kDa AMPD.
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AMPD kinetics. The kinetics of AMP deamination in the soluble fraction of control WG muscles consisted of a single linear phase in the double-reciprocal plot (Fig. 3). This indicates simple Michaelis-Menten kinetics and no cooperativity. The Km did not depend on the range of AMP concentrations over which it was determined and was ~1.5 mM (Table 3).
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-GPA treatment induced biphasic AMPD kinetics in the soluble cell
fraction of WG muscle (Fig. 3). For simplicity, we chose to quantitate
this response as two distinct linear kinetic phases: one of lesser
slope in the AMP concentration range of 0.04-0.15 mM and the other
of greater slope in the 0.2-15 mM range (Fig. 3, Table 3). The
Km over the AMP
concentration range 
0.15 mM was decreased at the 1-wk time point, and
the decrease was exaggerated as the time course progressed, to a
maximum of ~45-fold lower than control at 7 wk (Fig. 3, Table 3). The
result of the kinetic change is that at low AMP concentrations a
greater percentage of the available capacity
(%V15 mM)
is active in -GPA-treated muscle than in control muscle (Fig. 3,
Table 4), i.e., the molecular activity of
the AMPD enzyme molecule is increased. The
Km in the higher
AMP concentration range (0.2-15 mM) was also decreased during
-GPA feeding, but to a relatively modest extent (to approximately one-half of control), and this was significant only after 5 wk (Table
3). The concave hyperbolic shape of the double-reciprocal plot for
-GPA-treated WG (Fig. 3) implies negative cooperativity in the AMPD
reaction.
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-GPA-treated WG eliminated the
low-Km kinetic
phase (Fig. 4). This resulted in kinetics
with a half-saturating substrate concentration
(S0.5) of ~3 mM, similar to
the Km found for
control muscle (Table 3). The kinetics of acid phosphatase-treated
-GPA WG samples were distinct from those of the
control, however, because they were slightly convex (implying slight
positive cooperativity). Furthermore, a much lower
%V15 mM
was elicited at low AMP concentrations in the phosphatase-treated
-GPA extracts than in control extracts (compare scale of ordinate in
Fig. 4 to that of Fig. 3 and see Table 4).
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-GPA treatment had no effect on AMPD kinetics in the particulate fraction of WG muscles using either
method of preparation.
AMPD immunoprecipitation.
In addition to the skeletal muscle isoform of AMPD, WG muscle
homogenates contain small amounts of cardiac and nerve isoforms (21).
This raises the possibility that changes in the relative expression of
nonskeletal muscle AMPD isoforms could account for the kinetic
differences we observed. To address this issue, immunoprecipitation was
used to assess the fractional contribution of the skeletal muscle AMPD
isoform to the homogenate AMPD capacity in control and -GPA-treated
WG muscle. Immunoprecipitation using anti-skeletal muscle AMPD isoform
antibody removed similar fractions of the AMPD capacity from control
and 7-wk -GPA-treated WG samples (91.3 ± 0.4% and 88.5 ± 0.5%, respectively; n = 3 per group).
The isoform specificity of the antibody was confirmed by the
observation that none of the AMPD capacity from heart samples (which
contain only the cardiac AMPD isoform; Ref. 21) was immunoprecipitated
by the anti-skeletal muscle AMPD isoform antibody
(n = 3).
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DISCUSSION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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-GPA feeding results in the displacement of Cr and PCr from skeletal
muscle by -GPA and -GPA-P. In spite of the impaired CK reaction,
steady-state muscle force production is normal, endurance performance
is excellent, and steady-state energy balance is well maintained during
contractions. Similarly, the normal high rates of AMP deamination that
occur during intense muscle contractions are found in -GPA-treated
muscle, in spite of an ~80% reduction in the content of AMPD protein
(23). The findings of this study indicate that the induction of unique,
high-affinity AMPD reaction kinetics is available to compensate for the
reduced enzyme protein and allow the normal high rates of AMP
deamination to occur in contracting -GPA-treated muscle. The
observation that in vitro phosphatase treatment eliminates this kinetic
effect implicates phosphorylation in the regulation of AMPD in vivo.
AMPD enzymatic capacity is directly proportional to 80-kDa
abundance.
The direct relationship between enzymatic capacity of AMPD and 80-kDa
abundance during -GPA treatment illustrated in Fig. 2 suggests that
the loss of enzymatic capacity is due to a loss of 80-kDa enzyme
protein in muscle. The predicted AMPD capacity in the absence of 80-kDa
AMPD (the y-intercept) is
near zero (Fig. 2), even though 60- and 56-kDa AMPD species are
increased 20- to 40-fold compared with control (Table 2). Furthermore,
the slope of the AMPD capacity-abundance relationship over time (Fig. 2) was not different from that for control muscle in which 60- and
56-kDa AMPD species are essentially absent (see
RESULTS, AMPD Western
blots). These results suggest that the AMPD capacity
is dependent on the abundance of the 80-kDa AMPD protein and
independent of the 60- and 56-kDa forms, although we cannot completely
eliminate the possibility that the lower-molecular-mass species may be
active in a complex with some other intracellular factor.
-GPA (1). It
is instead likely that the decreased amount of AMPD protein occurs
within the existing muscle fibers. This may be part of a coordinated
series of changes that also affects the content of mRNA, protein,
and/or enzymatic activity of other components involved in
fast-twitch skeletal muscle energy transduction. These other components
include 
-actin (9), parvalbumin (12), the GLUT-4 glucose transporter
(14), and many glycolytic and mitochondrial oxidative enzymes (8, 9,
18).
The observation that -GPA treatment did not affect the AMPD mRNA
level (23) suggests that transcription of the AMPD gene is not
impaired. If translation of the AMPD mRNA is likewise not impaired,
AMPD protein synthesis rate is expected to be normal. This implies that
the degradation rate of AMPD protein may be increased by -GPA
treatment to account for the lower 80-kDa AMPD abundance. In support of
this argument is the increased abundance of lower-molecular-mass
species (60 and 56 kDa; Fig. 1, Table 2) that are probably degradation
products of the 80-kDa AMPD.
-GPA treatment alters the kinetics of AMPD from
fast-twitch muscle.
The induction of
low-Km kinetics
in the soluble fraction of WG by -GPA treatment was progressive with
treatment time to an apparent steady state after 3 wk (~45-fold
reduction in Km
assessed at low AMP concentrations, i.e., 0.15 mM; Table 3). The
inflection point of the double-reciprocal plot (at ~0.15 mM) did not
change as the Km
was progressively lowered, suggesting that the kinetic alteration did
not affect all AMPD molecules gradually over time. Rather, it is likely
that the individual alterations enveloped a greater number of AMPD
molecules over time, until all molecules were altered to yield the
high-affinity Km
of ~0.03-0.04 mM (Table 3). The high-affinity kinetics observed
at AMPf 0.15 mM is a reflection
of increased available AMPD molecular activity. As a result, the
predicted soluble AMPD activities of -GPA and control muscle
(extrapolated using the kinetic equations describing the data at AMP
concentrations 0.15 mM in Figs. 3 and 4) are similar at low,
physiologically relevant concentrations of
AMPf (i.e., 0.1-10 µM AMP;
Ref. 4; Table 4). Furthermore, these data suggest that similar AMP
deamination rates observed in control and -GPA-treated WG muscle
during intense in situ contractions (23) are elicited at similar
AMPf concentrations. Thus the
kinetic alteration in AMPD, manifest as an increased molecular
activity, appears fully competent to offset the decrease in AMPD
abundance. It may be the most important factor preserving the observed
ability of -GPA-transformed fast-twitch muscle to deaminate AMP to
IMP (13, 23), which has been shown to be the predominant entry reaction
to adenine nucleotide degradation in skeletal muscle, occurring at
rates several thousandfold higher than that of the alternate AMP
disposal pathway: dephosphorylation to adenosine by cytosolic
AMP-5'-nucleotidase (2). This does not exclude the possibility
that AMPf is elevated in
-GPA-treated muscle or that such elevations may affect deamination in situ. For example, the earlier onset of deamination during intense
in situ contractions in -GPA-treated muscle (23) may be the result
of a higher AMPf concentration
near the onset of contractions due to the absence of a PCr buffer pool.
However, our results illustrate that an exaggerated increase in
AMPf is not an essential or sole
mechanism to account for the normal AMP deamination rate observed
in -GPA-treated muscle during extreme contraction conditions (23).
-GPA-treated WG was
immunoprecipitated by the skeletal muscle isoform-specific antibody. It
is also unlikely that the 60- and 56-kDa molecules are responsible for
the change in kinetic behavior of AMPD, since they likely are
catalytically inactive. The possibility that these molecules could form
heterotetramers with active 80-kDa molecules and that the kinetics of
such complexes could be biphasic is unlikely, since 60- and 56-kDa AMPD
molecules were not found as components of AMPD tetramers isolated in
native PAGE experiments (unpublished observations). It seems more
likely that the 80-kDa molecule itself is influenced by -GPA
treatment in a manner that produces the observed kinetic changes. No
naturally occurring tight binding effectors of AMPD are known, and
neither -GPA nor -GPAP affects AMPD activity (23). Other soluble
effectors would not be expected to account for the observations in
vitro because they would dissociate during extraction of tissues and
assay of the extracts (~2,000-fold dilution). Protein-protein
interactions and covalent modification of the 80-kDa enzyme are
possibilities because of the observed stability of the response to
dilution and over time in vitro. It has been reported that myosin
binding as a result of muscle stimulation affects AMPD kinetics in a
manner similar to that observed in the present study in response to
-GPA treatment (17). In unstimulated control muscle, however, we found that putative myosin binding of AMPD in the particulate cell
fraction did not induce this kinetic behavior. Thus there is some
unique aspect of intense muscle contractions that influences AMPD
kinetics. If simple myosin binding played a role in the -GPA-induced AMPD kinetic response, it would be expected to affect the kinetics of
the enzyme in the particulate cell fraction (myosin is a component of
the particulate material) and not in the soluble cell fraction. We
observed exactly the opposite response in the current study; the
particulate fraction kinetics were not affected, whereas those of the
soluble fraction were. Furthermore, the kinetics of soluble cell
fraction AMPD from -GPA-treated muscle were not affected by
ultrafiltration (0.22 µm), which has previously been demonstrated to
retain myosin-bound AMPD (17). This evidence undermines an obligatory
role of myosin binding in the -GPA-induced kinetic alteration in
resting muscle but does not discount the possible significance of
myosin binding during intense contractions as an important determinant
of AMPD kinetic behavior. The lack of effect of -GPA treatment on
particulate fraction AMPD kinetics implies either that the association
of AMPD with the particulate cell material protects AMPD from the
modification seen in the soluble fraction or that the modified AMPD
cannot bind to the particulate material. The possible influence of
other protein-protein interactions involving AMPD on its kinetics have
not been studied.
It is possible that the kinetic alteration of AMPD involves covalent
modification of the native 80-kDa molecule. The observation that
treatment of the soluble fractions of -GPA-treated muscle with a
nonspecific acid phosphatase eliminates the high-affinity, low-Km kinetic
phase (Fig. 4) suggests that phosphorylation-mediated events control
the kinetic characteristics of skeletal muscle AMPD in vivo.
Phosphorylation may therefore be responsible for the appearance of the
low-Km phase in
-GPA-treated muscle. This is supported by the results of Tovmasian
and co-workers (22), who demonstrated that phosphorylation of purified
80-kDa skeletal muscle AMPD by protein kinase C in vitro resulted in a
relatively modest (~65%) reduction in
Km at higher
(0.1-1 mM) AMP concentrations. Our observation of an ~55%
reduction in Km
at high (0.2-15 mM) AMP concentrations with -GPA feeding (Table
3) agrees with the data of Tovmasian et al. (22). Unfortunately,
Tovmasian et al. did not evaluate enzyme kinetics over a low AMP
concentration range (i.e., <0.1 mM) in their purified, phosphorylated
AMPD preparation, so direct comparison to our kinetic data cannot be
made. On the basis of our data, a substantial reduction (i.e., 45-fold)
in Km of purified
skeletal muscle AMPD evaluated at more physiologically relevant
AMPf concentrations is expected to
result from this putative AMPD phosphorylation(s).
From the current results it is not possible to determine whether the
influence of -GPA treatment on AMPD involves direct effects of
-GPA on pathways that control AMPD abundance, activity, and kinetics
or whether the effects are indirect, as a function of intracellular
energetics. Direct effects of -GPA could be ruled out if similar
changes to AMPD occur in CK knockout muscle in which CK flux is
eliminated in the absence of Cr analogs. As has been previously
proposed (12), intracellular energetics could regulate muscle phenotype
through alterations of cellular ATP, ADP,
Pi,
H+, or
Ca2+ levels. Disruptions in these
due to -GPA treatment may therefore be directly or indirectly
involved in the signaling pathway that causes the observed alterations
in AMPD.
In summary, phosphorylation of AMPD could be important in the in
vivo control of AMP deamination, by increasing the molecular activity
of the enzyme at physiological
AMPf concentrations. Such a
kinetic alteration occurred when CK-dependent buffering of the ATP pool
was impaired by -GPA treatment. This alteration appears competent to
compensate for the decreased AMPD abundance that also results from
-GPA treatment, to allow normal in situ AMP deamination rates. The
involvement of this kinetic alteration in the response of AMPD to other
physiological states in which adenine nucleotide management is
challenged and the mechanism of involvement of phosphorylation in the
control of AMPD kinetics remain to be determined.
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ACKNOWLEDGEMENTS |
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We gratefully acknowledge the excellent technical assistance of Judy Freshour. We thank R. L. Sabina (Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI) for generously supplying the anti-skeletal muscle AMPD antibody.
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FOOTNOTES |
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This study was supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant AR-21617.
J. W. E. Rush was the recipient of a Natural Sciences and Engineering Research Council of Canada postgraduate scholarship B predoctoral fellowship.
Current address of J. W. E. Rush and R. L. Terjung and address for reprint requests: Department of Veterinary Biomedical Sciences, E102 Vet. Med. Bldg., University of Missouri-Columbia, Columbia, MO 65211.
1 A large fraction of the total ADP and AMP pools is bound to protein in vivo. The subscript "f" refers to free nucleotide that is available for the indicated reactions.
Address reprint requests to R. L. Terjung.
Received 2 September 1997; accepted in final form 3 November 1997.
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REFERENCES |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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