From www.bloodjournal.org by guest on July 31, 2017. For personal use only.
CONCISE
REPORT
Decreased
Erythrocyte
Nicotinamide
Abnormal
Pyridine
By Charles
RBCs
from
susceptible
defense
individuals
with
to
damage.
reactions
nicotinamide
are
that
RBC
demonstrate
that
in the
NADH/[NAD
RBCs
(P
R
FROM
(SCD)
to oxidant
Studies
oxidant
sickling
shortened
RBC
the
RBC
oxidant
survival
also
sickle
time
may
play
survival
damage
includes
S
of
in
normal
suggest
in the
and
the
Evidence
for
increased
membrane
decreased
glutathione
body
incubated
Heinz
pentose
phosphate
peroxide
likely
(Hb)
radical
sickle
RBC
have
been
hemolysis.9
a consequence
which
generation3
510.11
reductase
formation,7’8
shunt
RBC
activity,7
oxidant
of the inherent
shown
in vivo
to
have
as manifested
by
catalase
activity,2
(GR)
activity,7
increased
a relative
impairment
of
and
increased
damage
instability
in SCD
hydrogen
is most
of hemoglobin
results
in a concomitant
increase
in free
in association
with impaired
antioxidant
defense.”’7’9
stitute
These
met-Hb
From the Department
ofMedicine,
Harbor-UCLA
Medical
Center, University
of California
at Los Angeles
School
of Medicine,
Torrance.
Submitted
July 30, 1987; accepted
October 5, 1987.
Presented
at the National
Meeting
of the American
Federation
for Clinical Research,
San Diego. May 4, 1987.
Supported
by a grant from
the Sickle
Cell Disease
Research
Foundation
ofLos
Angeles
(C.R.Z.)
and by Grants
No. AM 36124
(N.A.L.)
and AM 14898 (KR. T.) from the National
Institutes
of
Health.
Dr Zerez is the recipient
of Individual
National
Research
Service
Award
No.
HL-07364
from
the National
Institutes
of
Health.
Address
reprint requests
to Charles R. Zerez, PhD, Department
of Medicine,
Cl-12, Harbor-UCLA
Medical
Center,
1 124 West
Carson St. Torrance,
CA 90502.
The publication
costs ofthis article were defrayed
in part by page
charge payment.
This article
must therefore
be hereby marked
“advertisement”
in accordance
with 18 U.S.C.
§1734 solely
to
indicate this fact.
Inc.
512
the
potential
had
NADPH]
that
these
sickle
RBCs
that
may
be
sensitivity.
may
sickle
a
The
have
further
erythrocyte.
Inc.
S is believed
(met-Hb)
defense
use
readily
ie, NADH
NAD
in their
globin.’2
and con-
plus
report
Because
A. Although
directly,
it has
S instability
by
the hypothesis
that sickle
RBC
relative
to the total NAD
(NAD1,
In addition,
dehydrogenase
that
sickle
relative
indicate
ratio
as GR,
and
are linked
to NADP,
we
RBC
may
also have
a
total
concentration.
that
because
enzymes
such
(G6PD),
to the
)
NADP
NADH/NADT
nicotito con-
form.’3
Hb A to met-Hb
) concentration.
in NADPH
NADPT
denatured
sequence
reduced
antioxidant
defense
dehydrogenase
6-phosphogluconate
tested
the hypothesis
and
this
been demonstrated
as a cause
of Hb
we tested
in NADH
in this
oxidaforma-
Hb A,’#{176}”
Hb S may be oxidized
than
has not
suggested
other critical
RBC
glucose-6-phosphate
stable,
than
Hebbel.’4
Thus,
have a decrease
NADPH
ultimately
interrupt
to its more
S more
plus
through
the subsequent
mechanism
to reverse
this process.
reduced
nicotinamide
adenine
dinu-
unstable
this possibility
recently
been
to occur
with
and, to a limited
extent,
reduced
dinucleotide
phosphate
(NADPH)
back
Hb S is more
sented
& Stratton,
Thus.
nucleotides
for
of Hb
(NADH)
adenine
decrease
0006-4971/88/7102-0016$3.00/0
pyridine
RBCs
+
oxidant
& Stratton.
the first
reductases
cleotide
namide
ie,
0 1 988 by Grune
these
tion
of hemichromes
and
Methemoglobin
reductases
to met-Hb
addition,
redox
age.
content
sickle
demonstrated
cell
sickle
NADP
.00005).
<
increased
to methemoglobin
tion.7’8
in vitro
antioxidant
defense
glutathione
peroxidase
and
their
Denaturation
tion
vert
In
NAD
although
total
NADPH/[NADP
to
consequences
lipid peroxidation,”2’4
increased
membrane
protein
thiol oxidation,5
and
a decreased
reduced
glutathione
concentraimpaired
decreased
(P
controls
in
by Grune
contrast.
in the
in the
related
a decrease
1988
disease
role
of vasoocclusion,
in SCD.”38
in SCD
a
In
RBCs
normal
alteration
reticulocyte
metabolic
are more
an important
development
had
R. Tanaka
with
not
and
Disease
.00005).
<
Potential
with
cell
and
(P
were
changes
normal
compared
have
Kouichi
increase
High
changes
Cell
a significant
reflection
data
decrease
with
damage
than are RBC
from
in this and other
laboratories
sensitivity
process,
by
+
RBCs
content
ratio.
the
Our
had
no significant
tested
a significant
with
a shortened
compared
we
and
RBCs
nucleotides
as manifested
sickle
NAD
normal
more
nicotinamide
compared
J. Lee,
RBCs
erythrocytes.
ratio
INDIVIDUALS
have
susceptible
individuals.’
that
in total
and
are
Sandra
Redox
in Sickle
antioxidant
NADPH/[NADP
have
NADHI
Interestingly.
increase
BC
and
RBCs
+
pyridine
(NADP).
in sickle
sickle
.00005).
<
significant
the
key
potential
NADH]
is decreased
disease
(NAD)
redox
+
ratios
to
phosphate
the
NADH/[NAD
NADPH]
cell
Dinucleotide
Content
Neil A. Lachant,
Because
dinucleotide
dinucleotide
hypothesis
Nucleotide
R. Zerez,
sickle
linked
adenine
adenine
the
oxidant
Adenine
sickle
RBC
and
an increase
AND
METHODS
NADP
(NADPT,
The
data
have
a decrease
in their
preNADT
concentrations.
MATERIALS
Blood
obtained
samples.
After obtaining
informed
consent,
blood was
by routine
venipunctune
with hepanin
(I 5 U/mL
whole
blood)
as an anticoagulant.
Individuals
with SCD were adult homozygotes
(Hb SS) who did not have concomitant
RBC G6PD
deficiency.
Normal
subjects
and individuals
with neticulocytosis
were used as controls.
None of the subjects
received
a blood
transfusion
within the 3 months before the study.
Determination
of pyridine
nucleotides.
The concentrations
of
the pynidine
nucleotides
in RBC were determined
by using the
method
of Zerez
et al.’5 Twenty
microliters
of blood were mixed with
1,980 iL of a solution
containing
10 mmol/L
nicotinamide,
20
mmol/L
NaHCO3,
and 100 mmol/L
Na2CO3 at 0#{176}C.
The mixture
was frozen in a dry ice-acetone
bath, thawed
quickly
in a room
temperature
water bath, and then chilled to 0#{176}C.
To destroy NAD
and NADP,
700 zL of this mixture
was incubated
at 60#{176}C
for 30
minutes and promptly
chilled to 0#{176}C.
Both the heat-treated
extract,
Blood,
Vol
71,
No 2 (February),
1988:
pp 512-5
15
From www.bloodjournal.org by guest on July 31, 2017. For personal use only.
RBC,
NAD.
AND
NADP
513
IN SCD
which contained
only NADH
and NADPH,
and the untreated
extract,
which contained
NADH,
NAD,
NADPH,
and NADP,
were immediately
analyzed
by using spectrophotometnic
cycling
assays.’5 The concentrations
of NAD
and NADP
were obtained
by subtracting
the concentration
of NADH
or NADPH
in the
heated extract
from the concentration
of NAD1 or NADPT in the
unheated
extract.
which
NADT,
was
either
Sickle
Sickle
RBC
increase
(8%
in the
RBC
(2.0%
to 54%
NAD1
reticulocytes)
concentration
reticulocyte
tration
(mean
RBC
was
count
1 SD)
±
42.2
±
10.5 nmol/mL
NADH
content
8.3,
(Fig
in normal,
43.0
10.6,
±
increase
HR
II RBC
in NADT
increase
in
The
HR
RBC
concentration
(Table
1).
46.7
8.8,
±
(Fig
content
NAD
1B),
in sickle
content.
Thus,
which
NADP1
content
by the
measurable
concenSCD
and
41.6
that
is due entirely
the
ratio
±
RBC
in all
however,
was
with normal,
indicates
RBC
1).
to the
Thus,
the
constant
concentration,
RBC compared
RBC
of
the
the increase
cant
(Table
coupled
should
sickle
RBC.
RBC
to quantitate
A
NADP
sought
observations.
HR
NADP1
not
II RBC
was
(Table
the
1). In
increase
content,
content
increase
in NADP
to measure
in trace
in
for only
given
not statistically
NADPH/NADP1
NADPH
is present
normal,
be accounted
in NADPH
able
with
content,
could
content
unchanged
increased
were
difficult
We next
RBC
be a concomitant
We
compared
the
I, and
increase
the
in the
However,
no significant
NADPH/NADPT
ratio
in NAD1
in sickle
because
our
HR
increase
in NADP
1). The
with
there
to the
NADH/
normal,
with
1C).
increase
in sickle
contrast
(Fig
potential,’6
compared
with normal,
HR I, or HR II RBC
the
NADPH
content
was also
HR II RBC
(Table
were
found
in
SCD,
redox
RBC
II RBC
a significant
significantly
between
II, and
I, or HR
had
with
normal
of cellular
in sickle
compared
In addition,
a significant
NADH
I, HR
packed
RBC,
respectively.
appeared
to be remarkably
cohorts
examined.
The NAD
significantly
increased
in sickle
I, or
IA).
HR
HR I, or
differences
and with RBC
from
individuals
with a moderately
to 6.5%, HR I) or a markedly
(1 8.7% to 76.0%,
HR II)
increased
HR
had
compared
indicator
significantly
normal,
increased
RESULTS
is an
decreased
that
signifiratio
suggest
that
content
in
such
an increase
amounts
that
are
accurately.’7
to exclude
No
potential
differences
sources
were
observed
of error
in
for
RBC
0
0
10
150
150
tm
.-
18
‘-7
cr
A
0
a
A
1oo
A
+t
h:o
40
z
I
z;
#{176}
0
0
-‘-0
0
:
Too
a
IA
1000
IA
A
T#{176}:#{17
z
0
50
A
50
#{176}
0
I t t
SD
T0
T0o
.
83.0k
5.4
L____i
(%)
94.77
7.3
L_____J
HR I
Normal
RElICS
A
a
A
.
763fl28
0
NTA
0.5-1.1
0
L____.J
HRfl
2.0-6.5
,
127.8±22.9
SCD
18.7-76.0
8.1-53.7
7 SD34.1
t6.9
L___J
Normal
RETICS(%)
0.5-1.1
40159.7
L___J
HRI
2.0-6.5
48.1
±
15.5
L__J
HRU
18.7-76.0
86.3t
16.4
L___J
SCD
8.1-53.7
C
0.7
A
0.6
1
a
I:
o.5
A
To
IA
±00
I
‘a
A
0.4
a
a
T
z
Ia
0.3
t00
10
0.2
0
0.1
,.!ISD’
0.552
5 0.058
0.517
± 0.080
0.500
7 0.136
0. 325
5 0.060
0
Normal
RETICS(’/.)
0.5-1.1
HR
I
2.0 - 6.5
HR
18.7
II
SCD
-76.0
8.1 - 53.7
Fig 1 .
NADT and NAD
concentrations
and NADH/NADT
ratio
in RBC from normal subjects.
individuals
with SCD. and individuals
with
reticulocytosis
(HR I and HR II). (Panel A) NADT concentration.
T test:
normal
v SCD. P < .00005;
HR I v SCD. P < .0001 ; HR II v
SCD. P < .02. (Panel B) NAD
concentration.
Ttest:
normal
v SCD.
p < .00005;
HR I vSCD.
P < .00005; HR II vSCD.
P < .003. (Panel C)
NADH/NAD1
ratio. T test: Normal
v SCD. P < .00005; HR I i’ SCD.
P < .00005;
HR II V SCD. P < .007.
From www.bloodjournal.org by guest on July 31, 2017. For personal use only.
514
ZEREZ
Table
I
NADP
.
Concentrations
NADPH/NADP
and
With
SCD
and Individuals
No.rmal(n
1 SD
±
0.9
Range
HRI(n
Subjects.
0.4
±
3.3
1 SD
±
39.5
3.7
±
39.2
33.6-48.2
Pack ad RBCI
NADP
3.9
±
0.32
31.4-45.8
47.4
Mean
Ttest:
28.2
1 SD
±
46.4
15.4
±
normal
vSCD,
NADP:
SCD
.05.
<
P
<
pyridine
trations
nucleotides,
of added
was
obtained
and
and
NADP
NADPH
full
NAD,
HR I vSCD,
recovery
NADH,
in unheated
P
60.6
11.1
±
.02;
<
extracts,
from
this
patients
recovery
with
RBC,
added
NAD,
recovered
with yields
whereas
HR II vSCD,
concenNADPH
added
experiment
SCD.
NAD
NADH
in both
by using
In unheated
NADH,
ranging
100%. Thus,
the recovery
identical
in normal,
high
samples.
This
nucleotide
in recovery
suggests
content
of the
In addition,
NADP,
between
P
.05.
<
NADPH:
normal
under
alkaline
NADT
ratio
ratio
data
the
blood
the changes
blood reflect
that
sickle
can
NADH
conditions,’8
the
combined
with
in sickle
are not
mediate
during
decrease
the
in
of
the
NADPH/
RBC
provides
additional
due to an artifact
of the
the
RBC
RBC
NADH/
unchanged
nucleotide
extraction
or assay systems.
We as well as other
investigators”8”9
to determine
oxidation
evidence
pyridine
have
pyridine
pyridine
used
nucleotide
whole
content
is
plasma.
nucleotide
been
due to
content.
We
contents
shown).
Thus,
changes
found
although
content
in
no
between
normal
More importantly,
blood
unlikely,
in sickle
whole
the
blood
the plasma
pyridine
differences
in NADT
and
plasma
is used,
how-
abnormal
might
or
have
nucleotide
NADPT
sickle
plasma
(data
NADT
and NADP1
not
were
.02;
<
HR
less than
1 nmol/mL
plasma,
an insignificant
contribution
nucleotide
that
content
content.
sickle
RBC
These
have
as manifested
results
an abnormal
by a decrease
with
normal
nucleotide
reflection
statistical
and
groups
did have a slight
ratio
and
slight
increases
contents
in
compared
with
normal
RBC,
sickle
decrease
in the NADH/NADT
in NADT
and NADPT
contents
RBC.
These
results
suggest
abnormalities
found
of a younger
mean
significance
in RBC
ratios
decrease
in the
in NAD1
and
between
HR
II
that
the
in sickle
RBC
RBC
age.
The
pyridine
nucleotide
and
SCD
RBC
ratio
and
compared
pyridine
are not a
finding
of
content
confirms
the
latter
contents
may
cause
hypothesis.
increases
in NAD
and
NADPH
additional
and perhaps
adverse
metabolic
consequences
in
sickle
RBC.
For example,
because
NADPH
is a potent
because
whole
control
had a greater
greater
increases
pyridine
when
P
significant.
an increase
in NAD,
the increase
in NADP1
was accounted
for by an increase
in NADPH.
Although
the high reticulo-
inhibitor
possible
content
HR I vSCD,
HR II, not
the NADH/NAD1
ratio
and by increases
in the NADT,
NAD,
NADP1,
and NADPH
contents.
It is interesting
that
although
the increase
in NADT was accounted
for entirely
by
because
previous
studies
have shown that RBC have at least
a 100-fold
higher
concentration
of pyridine
nucleotides
than
do leukocytes.2#{176} Another
possible
contributor
to “RBC”
nucleotide
.00005;
<
in pyridine
nucleotide
content
in
changes
in RBC
pyridine
nucleo-
demonstrated
nucleotide
The
have
0.019
±
DISCUSSION
NADPT
the
0.978
content.
in pyridine
extraction
P
make
pyridine
0.048
±
0.941-1.01
HR I, and
to the whole
cyte RBC
NADH/NAD1
abnormalities
1.0
±
vSCD,
SCD vnormal,
nucleotides
SCD
blood
RBC were not due to differences
during
the extraction
process.
hemoglobin
and
and NADP
NADH
and
between
91%
0.983
0.910-1.03
1.3
suggest
whole
tide
2.2
±
-0.6-2.8
both found
at concentrations
which
indicates
that they
We
of
and NADPH
96% and 100%.
of added
pyridine
reticulocyte,
and
that
in sickle
nucleotides
because
NADPH
NADPT
that
our
0.035
±
0.938-1.03
0.72
11.1
±
NADPH/NADP1:
blood
extracts
In heated
extracts
of sickle RBC, added
NAD
were
destroyed
completely,
whereas
added
NADPH
were recovered
with yields
ranging
pyridine
0.044
±
0.977
-1.4-4.2
43.4-75.7
whites,
Orienand assay of
of physiological
NADP,
and
8.1
±
36.8-56.1
HR I, and HR II, not significant.
were completely
destroyed
and added
were fully recovered
in heated
extracts
we repeated
samples
both
1.8
±
1.6-3.1
-
and high-reticulocyte
blood samples.’5
To ensure
full
of pyridine
nucleotides
during
extraction
of sickle
recovery
ever,
0.995
0.935-1.10
1.0
9.8
±
47.9
44.4-76.9
.00005;
vnormal,
7.1
±
61.9
pyridine
nucleotide
content
or ratios in normal
tals, or blacks.
Using our method
for extraction
blood
1.8
±
-3.9-2.8
35.0-61.4
37.9-56.9
8.1-53.7
NADP1:
P
48.7
26.2
±
11.3-76.0
Range
normal
9.4
±
36.2-64.5
32.9
1 SD
±
Range
SCD(n -9)
sickle
were
NADPH/NADP7
-5)
Mean
II vSCD,
0.9
±
2.0-5.0
HRll(n
RBC,
Individuals
-8)
Range
of
(nmol/mL
Normal
NADPH
NADPT
0.5-1.1
Mean
and
was
Reticulocytosis
16)
-
Mean
1%)
Reticulocytes
in RBC From
With
N ucleotides
Pyridine
Subjects
Ratio
ET AL
of G6PD,2’
mechanism
phosphate
shunt
NAD
hyde-3-phosphate
NAD
content
the increased
for the relative
activity
in
is a rate-limiting
dehydrogenase
is a possible
NADPH
impairment
sickle
content
is a
in pentose
RBC.7
factor
reaction,22
mechanism
Furthermore,
in the
for
glyceraldethe
increased
the
increased
glucose
consumption
rate ofsickle
RBC (Lachant,
Zerez
Tanaka,
unpublished
results).
The decrease
in the NADH/NAD1
ratio
suggests
sickle
RBC have a decrease
in the NAD
redox potential.
and
that
In
From www.bloodjournal.org by guest on July 31, 2017. For personal use only.
NAD,
RBC,
AND
contrast,
NADP
we observed
NADPT
minor
515
IN SCD
no apparent
changes
in the
NADPH/
in
ratio
in sickle
RBC.
This
is consistent
with
role
that
NADPH
methemoglobin
reductase
believed
decrease
to play in the
in NAD
redox
increased
oxidant
the
is
RBC.’3
Our results
suggest
that
potential
may be a manifestation
sensitivity
and
increased
Hb
the
of
S instability
sickle
RBC.
Studies
are
laboratory
to determine
the
NAD... and NADPIcontents
We
are
currently
under
mechanism
in sickle
for
RBC.
ACKNOWLEDGMENT
to Alyson
M. Fouse
grateful
for
way
the
in
our
increases
expert
in
secretarial
assistance.
REFERENCES
Chiu D, Lubin B: Abnormal
vitamin E and glutathione
peroxidase levels in sickle cell anemia. Evidence for increased
susceptibility
to lipid peroxidation
in vivo. i Lab Clin Med 94:542, 1979
I
.
2.
Das
5K,
Nair
RC:
Superoxide
dase, catalase
and lipid peroxidation
cytes. Br i Haematol
44:87, 1980
3.
Hebbel
RP,
Eaton
JW,
dismutase,
glutathione
of normal
and sickled
Balasingam
M, Steinberg
peroxi-
erythro-
MH:
Spon-
taneous
oxygen radical
generation
by sickle enythnocytes.
i Clin
Invest 70:1253,
1982
4. Jam 5K, Shohet
SB: A novel phospholipid
in irreversibly
sickled cells: Evidence for in vivo peroxidative
membrane
damage in
sickle cell disease. Blood 63:362, 1984
5.
Rank
BH,
Canlsson
membrane-protein
75:1531,
i, Hebbel
thiols
RP:
in sickle
Abnormal
redox
erythrocytes.
status
J Clin
of
Invest
1985
6. Rice-Evans
C, Omorphos
SC, Baysal
and oxidative damage.
Biochem J 237:265,
E: Sickle
1986
cell membranes
Lachant
8.
Wetterstroem
NA,
Davidson
N, Brewer
WD,
Gi,
Tanaka
Warth
KR:
JA,
K: Relationship
of glutathione
levels and Heinz
irreversibly
sickled cells in sickle cell anemia.
103:589,
Mitchinson
A, Near
body formation
to
i Lab Clin Med
1984
9. Lachant
NA, Tanaka
KR: Antioxidants
in sickle cell disease:
The in vitro effects of ascorbic acid. Am i Med Sci 29:3, 1986
10. Asakuna T, Ohnishi
T, Friedman
5, Schwartz
E: Abnormal
precipitation
of oxyhemoglobin
S by mechanical
shaking.
Proc NatI
Acad Sci USA 71:1594,
1974
I 1. MacDonald
VW, Chanache
5: Drug-induced
oxidation
and
precipitation
of hemoglobins
A, S and C. Biochim
Biophys Acta
701:39,
12.
1982
Babior
BM:
Oxidizing
radicals
and
red cell destruction,
iE
ir, Walford
R, Harman
D, Miquel
i (eds):
Free
Radicals,
Aging,
and Degenerative
Diseases. New York, Liss, 1986, p 395
1 5. Zerez CR, Lee Si, Tanaka
KR: Spectrophotometric
determination of oxidized and reduced pyridine
nucleotides
in erythrocytes
using a single extraction
procedure.
Anal Biochem
164:367,
1987
16. Marshall
WE, Omachi
A: Measured
and calculated
NAD/
NADH
ratios in human erythrocytes.
Biochim Biophys Acta 354:1,
1974
Impaired
pentose
phosphate
shunt function
in sickle cell disease: A potential
mechanism
for increased
Heinz
body
formation
and membrane
lipid
peroxidation.
Am i Hematol
15:1, 1983
7.
Wallach
DFH (ed): The Function of Red Cells: Erythrocyte
Pathobiology. New York, Liss, 1981, p 173
13. iaffe ER: The formation
and reduction
of methemoglobin
in
human erythrocytes,
in Yoshikawa
H, Rapoport
SM (eds): Cellular
and Molecular
Biology of Erythrocytes.
Baltimore,
University
Park,
1974, p 345
14. Hebbel
RP: Autoxidation
and the sickle erythrocyte
membrane: A possible model of iron decompartmentalization,
in Johnson
in
17. Kirkman
HN, Gaetani GD, Clemons
EH, Mareni C: Red cell
NADP
and NADPH
in glucose-6-phosphate
dehydrogenase
deficiency. i Clin Invest 55:875, 1975
18. Burch HB, Bradley
ME, Lowry OH: The measurement
of
tniphosphopynidine
nucleotide
and reduced
triphosphopyridine
nucleotide
and
the
role of hemoglobin
in producing
erroneous
tniphosphopynidine
nucleotide
values. i Biol Chem 242:4546,
1967
19. Sander BJ, Oelshlegel
Fi in, Brewer Gi: Quantitative
analysis of pyridine
nucleotides
in red blood cells: A single-step
extraction
procedure.
Anal Biochem 71:29, 1976
20. Gross RT, Schroeder
EA, Gabnio BW: Pynidine nucleotides
in erythrocyte
metabolism.
J Clin Invest 45:249, 1966
21 . Luzzatto
L, Testa U: Human
erythrocyte
glucose-6-phosphate dehydrogenase:
Structure
and function in normal and mutant
subjects.
Curr Top Hematol
1 : I 1978
,
22.
Mills
GC,
Hill
FL:
Metabolic
erythrocytes.
The role of glyceraldehyde
Arch Biochem Biophys 146:306, 1971
control
mechanisms
phosphate
in human
dehydrogenase.
From www.bloodjournal.org by guest on July 31, 2017. For personal use only.
1988 71: 512-515
Decreased erythrocyte nicotinamide adenine dinucleotide redox potential
and abnormal pyridine nucleotide content in sickle cell disease
CR Zerez, NA Lachant, SJ Lee and KR Tanaka
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