(CANCER
RESEARCH
27 Part 1, 2153-2158, November
1967]
Conversion of Glucose to Lipids by Normal and Leukemic Leukocytes1
CONSTANTINOS
J. MIRAS,
NIKOLAOS
J. LEGAKIS,
AND
GABRIEL M. LEVIS
Department of Clinical Therapeutics, School of Medicine, University of Athens, \'as. Sofias & K. Lourou Streets, Athens 611, Greece
SUMMARY
The lipids of normal leukocytes and of leukocytes from chronic
myelocytic leukemia (CML), acute leukemia (AL), and chronic
lymphocytic leukemia (CLL), labeled in vitro from glucose-U-14C
(uniformly labeled with 14C) were analyzed by mild alkaline hy
drolysis, column chromâtography on Florisil, thin-layer ehromatography, and autoradiography. Most of the incorporated glucose
carbon in both normal and leukemic leukocyte lipids was found
in the glycerol moiety of the glycerides. The sphingoglycolipid
fraction was labeled with intact hexose, and the fatty acids also
contained a low portion of the total radioactivity. The initial rate
of incorporation into the total lipids of normal leukocytes was
higher than in leukemic leukocytes, whereas the incorporation
in the latter was of a longer duration. Thus, after a six-hour incu
bation, the incorporation into the CML and AL leukocytes was,
respectively, two and three times higher than that into the normal
leukocytes. Normal leukocytes and leukocytes from AL produced
carbon dioxide constantly for 6 hours while leukocytes from CML
and CLL produced carbon dioxide for shorter times. The per
centage of the total lipid radioactivity incorporated into
triglycéridesby normal leukocytes was higher than that incor
porated by leukemic leukocytes.
The sphingoglycolipid fraction of leukemic leukocytes was
found to contain a 10 times higher radioactivity than that of the
sphingoglycolipids of normal leukocytes. The presence of cold
galactose in the incubation medium produced a small dilution
effect on the incorporation of glucose-U-14Cinto the lipids of nor
mal leukocytes, whereas in most of the leukemic cases examined
it produced a marked decrease of incorporation of glucose-U-14C
into sphingoglycolipids.
INTRODUCTION
Most of the biochemical investigations of human leukocytes
related to the carbohydrate metabolism examine the mechanism
and control of glycolysis in normal and leukemic cells (3, 4, 8, 21).
Leukocytes utilize glucose mainly through the Embden-Meyerhof
pathway, lactate being the major product of glycolysis. To a
minor extent, glucose is catabolized through the pen tose path (2).
1This work has been partly supported by NIH Grant No. HE
10421.
2 Abbreviations used are: CML, chronic myelocytir leukenii:i;
AL, acute leukemia; CLL, chronic lymphocytic leukemia; PPO,
2,5-diphenyIoxazole;
POPOP, 1,4-bis[2-(5-phenylo.\azolyl)]-benzene; UDPG, uridine diphosphate glucose; U, uniformly labeled
(as in glucose-U-14C).
Received January 3, 1967; accepted July 5, 1967.
NOVEMBER 19G7
It has been shown that normal leukocytes utilize more glucose
and oxygen than leukocytes of chronic myelogenic leukemias (3).
The rate-limiting enzyme of glucose utilization in both normal
and leukemic cells was found to be he.xokinase (1).
Although most of the glucose entering the human leukocytes
can be found as lactate, it has also been reported that
polymorphonuclear leukocytes from rabbits can incorporate
glucose carbon into lipids (10, 25).
Previous publications from this and other laboratories pre
sented evidence that human leukocytes can synthesize lipids from
acetate (6, 16, 23). Comparative studies tetween normal and
leukemic cells have shown difference.! in acetate utilization for
phospholipid synthesis (16). Utilization of glucose by human
leukocytes for lipid synthesis has not been studied. Such studies
could at least help in establishing the pathway and extent of glu
cose conversion to lipids in normal leukocytes, an essential knowl
edge in studies on lipid metabolism under different conditions
of cell nutrition, in which leukocytes are used as representative
human cells. Comparison of the conversion of glucose to lipids
by normal and leukemic leukocytes could help in the elucidation
of the previously reported abnormal lipid syntheses of the
Ipukemic leukocytes (16).
Another reason prompting such comparative studies was the
finding lately reported by us (18) that the lipids of normal human
leukocytes comprise large quantities of ceramide dihexoside—a
class of sphingoglycolipids possessing haptenic activity found in
tumor cells (22).
Therefore, the present paper describes results from experiments
studying the conversion of glucose to lipids in normal and
leukemic cells.
MATERIALS AND METHODS
Clinical Material. Normal leukocytes were taken from six
healthy blood donors. The patients with leukemia were hospital
ized; most of those treated with cytostatic agents had been
receiving the drug for approximately 10 days prior to leukocyte
examination. (The experiments described in this paper were per
formed with leukocytes obtained from seven patients with chronic
myelocytic leukemia, five patients with acute leukemia of vari
ous types, and three patients with lymphocytic leukemia.) Diag
nosis was based on bone marrow examination.
Separation of Lrukocytrs. Leukocytes were obtained from
individuals fasted for 12 hours. Whole blood (4 volumes) was
collected in a flask containing 1 volume of a solution consisting
of 1.32% sodium citrate and 0.48% citric acid hydrate. Polyvinylpyrrolidone (10% in 0.9% sodium chloride) was added to
the mixture to produce a final concentration of polyvinylpyrrolidone of 1.4%; the leukocytes were obtained in a pure state
2153
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i'. ./. Aliras, N. J. Legakis, and G. M. Levis
resin (H+ form), and extracted
with chloroform.
The chloroform
phase was dried and placed on a silicic acid column (2 gm) (special
for lipid chromatography;
Bio-Rad Laboratories,
Richmond,
Calif.). Methyl esters of fatty acids formed by methanolysis of the
neutral glycerides and phosphoglycerides
were eluted from the
column with chloroform and the sphingoglycolipids with chloro
form :methanol (16:4, v/v). The resultant lipid fractions were
examined by thin-layer chromatography
followed by autoradiography of the plates. The water-soluble material taken after mild
alkaline hydrolysis was hydrolyzed further with hydrochloric
acid (4 N) for two hours at 110°Cin a sealed tube. Hydrochloric-
60
120
180
240
300
360
TIME (min)
CHART 1. Hate of incorporation of 11Cfrom uniformly labeled
ghicose-14C into the total lipids of normal human leukocytes.
Each point of the curve is the mean of (>experiments.The
standard
deviation of the mean is shown. Incubation took place as described
in Table 1.
by a procedure described elsewhere (18). The whole procedure of
separation, including centrifugations, took place at 4°C.
Incubation.
Leukocytes were suspended in a modified KrebsRinger-phosphate-buffered
solution of pH 7.3 (11) at a concen
tration of 1 X IO7 to 3 X IO7 cells per ml. Incubation was per
formed in the presence of 0.15 Minole glucose-U-14C (specific
activity 41 mc/mmole) per ml, in a modified McCarthney flask
(17), in 95% O2and 5% CO2 at 37°C,for different time periods,
under continuous shaking. Siliconized glassware and sterile condi
tions were used throughout the separation and incubation of
leukocytes. In some cases (where CO2 and lipids were estimated),
two similar flasks were incubated, one for 14C02 measurement,
the other for extraction of the lipids. Collection and counting of
14C02 was performed as described previously (17). The enzymatic
reactionin cases of measurement of lipid synthesis was interrupted
by freezing or immediate extraction of leukocyte lipids. The ex
traction of lipids from the whole incubation mixture was performed
according to Folch et al. (12). This method has been slightly modi
fied for the extractions of intact leukocytes (18). In the experi
ments presented hereby, the extractions took place as above cited,
while the four washings of the chloroform phase were performed
as described by Folch et al. (12) to eliminate water-soluble radio
activity present in the incubation mixture. A sample of the lipid
solution was evaporated to dryness in vials and the residue was
dissolved in 15 ml of 0.5% PPO,2 0.03% POPOP in toluene and
was counted in a Packard Tri-Carb liquid scintillation spectro
meter, model 3003.
Mild Alkaline Hydrolysis. This procedure consisted of the
treatment of the total lipids with weak alkali, extraction of the
alkali-resistant
lipids, and separation of these lipids by column
chromatography
on silicic acid. Total lipids were treated with a
mixture containing equal volumes of chloroform and NaOH, 0.6
N in methanol (9, 13, 26), for 1 hour at room temperature and
were then diluted with water, acidified with cation exchange
2154
acid was removed under reduced pressure and the residue
analyzed by ascending paper chromatography on Whatman No. 1
paper with n-butanol: acetic acid ¡water (74:19:5, v/v) (5); the
radioactive spots were identified by autoradiography.
Am
moniacal silver nitrate was used for detecting glycerol and
molybdic acid reagent for glycerophosphate.
The radioactivity
of the organic soluble fractions \va«counted as described for total
lipids. For the counting of the water-soluble material, 0.5 ml of
it was dissolved in 15 ml of 0.5% PPO, 0.03% POPOP in toluene:
ethanol (1:1, v/v). Quenching corrections were made, and the
channel ratio method was applied in order to have comparable
results between these countings and those of 14COz and lipids.
Florisil Chromatography.
Chromatography of lipids on
florisil (Floridin Co., Tallahassee, Fla.) column (5 gm, 1 cm, i.d.)
was used to separate the lipids into classes, as described
previously (18). The neutral glycerides were eluted with 40 ml
of chloroform ¡methanol (19:1); the sphingoglycolipids with 150
ml of chloroform: methanol (1:2); and the phosphoglycerides with
150 ml chloroform ¡methanol (1:2, v/v) plus 12.5 ml H2O. The
estimation of the volumes and the composition of the eluents
were established by monitoring the Chromatographie run by thinlayer chromatography.
Thin-Layer Chromatography.
Basic and neutral plates were
prepared according to Skipski et al. (24); the first were developed
with chloroform ¡methanol ¡acetic acid:H20
(80:15:3:2,
v/v)
and used for the detection of the phosphoglycerides and sphingo
glycolipids. The latter were developed with petroleum ether:
ether:acetic
acid (80:20:2, v/v) and used for the detection of
neutral glycerides and fatty acid esters. Radioactive spots were
identified by autoradiography.
The area of the plates of these
spots was scrubbed out and measured in the liquid scintillation
counter as a suspension in Thyxotropic gel.
Hydrolysis of sphingoglycolipids
and hexose chromatography
and determinations were informed as described previously (18).
RESULTS
Rate of Glucose Conversion to Total Lipids and Carbon
Dioxide. Preliminary experiments by which the kinetics of glu
cose conversion into lipids were examined showed that, in the
presence of 0.15 /¿moleof glucose-U-14C, the concentration of
leukocytes could be varied from 1 X IO7 to 3 X IO7cells per ml
of incubation mixture without any change in the linear rela
tionship between cell counts and incorporation into lipids.
The rates of incorporation of glucose-LT-14Cinto total lipids of
normal leukocytes based on a cell count are presented in Chart 1.
It is obvious that glucose carbon is incorporated into the lipids
at a high initial rate; approximately 75 percent of the incorporaCAXCE1Ì
RESEARCH VOL. 27
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Carbohydrate Metabolism by Leukocytes
28
>- ^
I- m
— u
24
> «O
K
o
C
20
< CM
2 b
~
O
E
o. 12-
84
6O
12O
180
240
30O360
TIME (min )
CHART2. Rate of incorporation of 14Cfrom uniformly labeled
glucose-14Cinto the total lipids of leukemic leukocytes. Curve 1,
chronic lymphatic leukemia subject, No. 13 of Table 1. Curve #,
chronic myelocytic leukemia subject, No. 4 of Table 1. Curve S,
acute monocytic leukemia subject, No. 8 of Table 1. Several onemi suspensions of leukocytes were incubated for different time
intervals, under the conditions described in Table 1.
tion of 6 hours is accomplished within the first 30 minutes of incu
bation. Representative incorporation curves for leukemic leuko
cytes are shown in Chart 2. These cells possess a lower initial
rate of incorporation of glucose carbon into the lipids, which,
however, is of a longer duration. As a result, the cases of chronic
myelocytic leukemia and of acute leukemia, irrespective of being
treated or not, incorporate a higher degree of radioactivity from
glucose-U-I4C than normal cases over a six-hour period of incu
bation (Table 1). Leukocytes from lymphatic leukemias have a
lower incorporation than normals, or other types of leukemia.
Since the incorporation is expressed on a cell count, the lower
values for these cases are partially due to the smaller size
of lymphocytes and, therefore, the effect of treatment cannot be
evaluated in these cases. The same table indicates that more glu
cose carbon is converted to carbon dioxide by normal leukocytes
than by cells taken from CML or CLL. Time course experiments,
which are not shown here, indicate that normal leukocytes pro
duce carbon dioxide from glucose with a constant rate up to the
sixth hour of incubation. Leukocytes from CML and CLL have
a lower initial rate and a shorter duration of carbon dioxide pro
duction. Leukocytes of acute leukemias show a higher initial rate
and duration of carbon dioxide production, and a higher overall
incorporation into lipids.
Distribution
of 14C into the Lipids Formed from
GIucose-U-14C. Carbon from glucose can be incorporated into
lipids, either as intact hexose into the glycolipids, or, after
degradation, as glycerol into the neutral glycerides and phosphogtycerides, or, via acetate, into fatty acids, cholesterol, and
sphingosine.
Following mild alkaline hydrolysis of the total lirids (Table
2) of normal leukocytes, most of their radioactivity was found
in the water-soluble fraction, which was identified as glycerol and
glycerol phosphate. The fatty acids and sphingoglycolipids con
tained minor quantities of radioactivity. The radioactivity of the
sphingoglycolipids, after strong acid hydrolysis, was found to be
in the hexose moiety.
Table 2 also indicates that leukocytes from leukemic patients
incorporate most of the glucose as glycerol but, in contrast to the
normal, show a considerably higher specific activity, measured
on a cell count basis, in the sphingoglycolipids, the radioactivity
being in the hexose moiety.
Column chromatography on Florisil was used for the separa
tion of the lipids into neutral glycerides, sphingoglycolipids and
and phosphoglycerides. The results shown in Table 3 demonstrate
that the extent of incorporation of glucose, either as glycerol or
as intact hexose in the lipids of normal cells, shows substantial
differences from that of the leukemic ones, irrespective of being
treated or not. Neutral glycerides were the major radioactive
constituents of the lipids of normal leukocytes. The average ratio
of the radioactivities of neutral glycerides to phosphoglycerides
after incubation of 3 hours was 2.65 for the normal, whereas the
ratios for CML and AL were, respectively, 1.08 and 0.28. A prom
inent finding confirming the results of the mild alkaline procedure
was that the sphingoglycolipid fraction of the leukemic cells had
a higher specific activity than the normal ones, based on a cell
count. Thus, the average incorporation for leukemic sphingo
glycolipids was 396 cpm/106 cells, whereas that of normal lipids
was 36 cpm/106 cells. The same conclusions may be drawn when
their values are compared as a percent of the total radioactivity
incorporated into total lipids. The radioactive constituents of the
major lipid classes, isolated by Fiorisi! chromatography, were
identified by thin-layer chromatography and autoradiography
and counted for raidoactivity. Thus it was found that for both
normal and cells from CML, incubated for 6 hours, triglycérides
were the only radioactive spot of the neutral glycerides; the phosphoglyceride fraction contained approximately 70% of their
radioactivity in the phosphatidyl choline spot, the rest being
distributed, almost equally, between the phosphatidyl serine and
phosphatidyl ethanolamine spots. The phosphoglyceride fraction
of cells from acute leukemias contained more than 95% in the
phosphatidyl choline spot; only in the case of No. 8 did the phos
phatidyl ethanolamine spot contain a portion of radioactivity
comparable to that of CML and normal cells.
The sphingoglycolipid fraction showed one double radioactive
spot, which coincided with the material spot of cerarnide
dihexoside and a second radioactive spot moving near the sol
vent front. This latter spot has been tentatively identified pre
viously as ceramide monohexoside (18). In addition to these
spots, the sphingoglycolipids from acute leukemias showed con
siderable radioactivity in the ceramide trihexosides and aminoglycolipid spots (18).
The time course of incorporation of glucose carbon into the
lipid fractions of leukocytes from a case of CML, separated by
chromatography on Fiorisi! columns, is shown in Chart 3. It can
be seen that the initial rate of incorporation into the phospho
glycerides is higher than that into the neutral glycerides.
Effect of Cold Galactose. Preliminary experiments with
normal leukocytes (15) showed that galactose-l-14C is also incor-
NOVEMBER 1967
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2105
C. J. Miras, N. J. Legakis, and G. M. Levis
TABLE 1
Incorporation of "C from Glucose-U-"C" into Total Lipids and CO2of Normal and Leukemic Leukocyted"
IO3.5
X
IO5.0
X
IO6.5
X
IO5.2
X
IO6.5
X
IO43.5X
IO48.0X
10»4.5
X
lipids
(cpm/10«
cells)780
dioxide
cells)64,000
(cpm/10«
of
Subject
tesNormalCMLCMLCMLCMLCMLCMLCMLA.
leukocj
No.123450789101112131415Type
170'1,2401,4807101,3602,3402,1101,000
±
3,000e20,40027,20019,000Mean
±
daysNoneMyleran,
8 mg, during 10
daysMyleran,
3 mg, during 3
daysNoneMyleran
4 mg, during 29
oftherapy
for 1 year —out
daysMyleran,
since 20
daysPurinethiol,
8 mg, during 11
±S.D.
value
5702,8302,0402,4902,7401,2502,270
±
CML120,000244,000Mean
for
L.A.mon.
IO41.2
X
L.A.mon.
L.A.
myel.
L.A.myel.
IO59.6X
IO42.7X
IO41.15X
3daysNoneNoneMethotrexate,
2 nig, during
10daysNoneCortisone,
5 mg, during
IO43.7X
L.CLLCLLCLLWBC0-9
myel.
±S.D.
value
AL9,8007,320Mean
for
H)42.5X
40daysCortisone,
40 mg, during
IO52.02X
20daysLeuceran,
40 mg, during
580770190220390
±
X IO5TreatmentNoneMyleran,
6 mg, during 15 daysCarbon
±S.D.
value
±320
for CLLTotal
"Abbreviations used: U, uniformly labeled (glucose-U-14C); CML, chronic myelocytic leukemia;
CLL, chronic lymphatic leukemia; A. Mon. L., acute monocytic leukemia; AL, acute leukemias; A.
Myel. L., acute myeloblastic leukemia.
6One-mi suspensions of leukocytes were incubated for 6 hours with 0.15 jumóleglticose-U-14C,specific
activity, 41 mc/mmole.
e The "COi>radioactivity represents the results of 3 experiments and that of lipids resulting from 0
experiments. The values given are means ±S.D.
porated into the sphingoglycolipida with the same initial rate as
glucose-U-14C; however, labeling of the sphingoglycolipids
with
galactose-l-I4C after prolonged incubation was three to five times
higher than that obtained with glucose. Upon this observation,
we tried to find out whether the increased labeling of sphingo
glycolipids in leukemic cells was eventually due to an increased
formation of galactose-U-14C from glucose-U-14C in these cells.
Therefore, as shown in Table 3, leukocytes were incubated with
i>-glucose-U-14O, in the presence of twice as much nonradioactive
D-galactose. Addition of nonradioactive galactose to the incuba
tion medium had a decisive dilution effect only in certain cases
of leukemic cells, all of which were treated with cytostatic agents.
This effect was expressed prédominently as a decrease of labeled
hexose incorporation into the sphingoglycolipids.
Effect of Glucosi- Added during Incubation.
The data of
Table 4 present experiments performed to explain the slowdown
of the rate of incorporation of glucose carbon into the lipids of
normal cells. As shown, addition of nonradioactive glucoses, fol
lowing incubation of leukocytes for one hour, produced a marked
2156
TABLE 2
Mild Alkaline Hydrolysis of the Total Lipids"
of
Subject
No.*NormalNormal281013Period
acids
incubation
radioactivity
lipids
(cpm/10«
cells)938614516018011
(cpm/10'
cells)8105009701410179089Sphingoglycominutesc360360360360360180Water-soluble
(cpmcells)1101834046077021Fatty
10«
0 Recovery of the overall procedure was 81-92%. Values are
corrected to 100% in order to express the incorporation as cpm/106
cells.
6 Numbers of leukemic patients correspond to those of Table 1.
c One-mi suspensions of leukocytes were incubated in the pres
ence of 0.15 Binóleuniformly labeled glucose-HC specific activity
41 mc/mmole.
CANCER
RESEARCH
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VOL. 27
Carbohydrate Metabolism by Leukocytes
TABLE 3
Incorporation of Uniformly Labeled Glucose-nC (Glucose-U-ltC)
into Lipid Fractions and Effect of Cold Galactose"
N'o.Normal0Normal6'*CMLNo.
Subject
glycerides
(cpm/10«cells)410
_«10
u
cells)155
(cpm/10'
cells)36
8
Gì
70140±
2.630
±
O g
6
921551805705107106000004103353808506703304904801453102Phosphoglycerides(cpm/10«
±
472001403804006406400304502260219063041067057053025021575Sphingoglycolipids
±
2.22405928013546037062019572017024025550310751420144012024089
±
72430±
o
3No.
3CNo.
4No.
4«No.
5No.
5"No.
6No.
6CNo.
7No.
7"ALNo.
8No.
8CNo.
9No.
9CNo.
10aNo.
10No.
10«No.
12CLLNo.
13No.
15Neutral
" One-mi suspensions of leukocytes were incubated for three
hoursin the presence of 0.15 Minole glucose-U-14C (specific activity,
41 mc/mmole), and the total lipids separated by Florisil chromatography. No. 9 and No. 10 were incubated for six hours; No. 10a
was incubated for three hours. The lipids of No. 5 were separated
by the mild alkaline hydrolysis procedure. Recovery from the
column based on cpm applied on it was 84 to 96%. Values are cor
rected to 100% in order to express the incorporation as cpm/106.
6 Results from four experiments with different subjects. Values
are means ±S.D.
<
X
K
E
4-I
e
&
o.
-I
2-
60
120
180
TIME
CHART3. Incorporation of uniformly labeled glucose-"C into
fractions of leukocytes from one case of chronic myelocytic leu
kemia (Subject No. 7 of Table 1). One-mi leukocyte suspensions
containing 1.7 X 10' cells were incubated with 0.15 pmole of uni
formly labeled glucose-14C. After incubation for different time
intervals, the lipids were extracted and separated by chromatography on Florisil(Xcolumns
into Sphingoglycolipids
neutral glycerides (O
• 0),
phosphoglycerides
X), and
O)'
TABLE 4
Effect of Added Uniformly Labeled Glucose-^C (Glucose-U-ltC).
During Incubation
Leukocytes from normal subjects, 1.4 X IO7cells per ml, were
incubated in the usual incubation medium, in the presence of
ghicose-U-HC, 0.15/miole (specific activity, 41 mc/mmole).
After 60 minutes of incubation, the reaction was stopped in two
of the flasks, to serve as measure of the lipid radioactivity of the
60 minutes. At that time, in separate flasks glucose-U-'*C was
added, as indicated. The flasks with the new additions, or without
additions, were further incubated for different time intervals, as
indicated. The figures presented in this table are mean values of
duplicate samples.
c Cold galactose, 0.3 /unióle,was added in the incubation medium.
Lipid radioactivity
fimoleNot 0.15
(cpm/10«cells),
min.750750Glucose-U-"C,
at 60
increase of the incorporation,
indicating that the intermediate
metabolism leading to the formation of trióse phosphate remained
active.
360
(mm)
radioactivity
cells)120
(cpm/10«
min.800
added
AddedLipid
min.850
2300,%0
DISCUSSION
The presented data clearly demonstrate that, under the experi
mental conditions used, intact human leukocytes can utilize glu
cose for lipid synthesis, mainly via the trio.se phosphate inter
mediate.
Normal and leukemic cells may be compared from different
points of view; thus, the lower initial rate and the longer duration
of incori ¡oration of glucose-U-14C into the lipids of leukemic cells
must be attributed to the lower rate of glucose utilization of these
cells (3). The finding that leukemic cells, when compared to
normal ones, incorporate a higher percentage of glucose carbon
into the phosphoglyceride fraction is in agreement with the results
of a previous study in this laboratory, according to which fatty
acids synthesized from acetate were also preferentially incor
porated into the phosphoglycerides (16). It can now be concluded
that the abnormality of lipid synthesis of leukemic cells lies in
the mechanism of utilization of D-a,/3-diglycerides for phospholipid synthesis.
Glucose, in addition to being incorporated into lipids via the
triósephosphate, is also found as intact hcxose in the sphingoglycolipid fractions. The material of this fraction in normal
human leukocytes constitutes 15 percent of the total lipids of the
cell and comprises very little ceramide monohexoside, while the
bulk of it consists of a mixture of ceramide lactoside and ceramide
galactosyl-galacto.se (18). The results presented in this paper pro-
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2157
('. ./. Miras, A . J. Legakis, and G. M. Lcvis
vide evidence as to an increased labeling with glucose-14Cof the
sphingoglycolipids by leukemic cells. It has been reported
recently (19) that increased amounts of UDPG were found in
leukocytes from chronic myelocytic and acute myeloblastic leukemias as compared to normal leukocytes; and that this finding
was not due to a reduction of the UDPG-glucosyltransferase
activity of the leukemic leukocytes (20). It is, therefore, probable
that the increased sphingoglyeolipid synthesis in leukemic leuko
cytes reported here is the result of an increased UDPG which is
generally involved in sphingoglycolipid biosynthesis (7). Uridine
diphosphate glucose is also the activated intermediate of glucose
during epimerization to galactose (14). This reaction, as indicated
in Results, may play a role in the increased incorporation of glucose-U-14C into the sphingoglycolipids of leukemic leukocytes.
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CANCER
RESEARCH
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VOL. 27
Conversion of Glucose to Lipids by Normal and Leukemic
Leukocytes
Constantinos J. Miras, Nikolaos J. Legakis and Gabriel M. Levis
Cancer Res 1967;27:2153-2158.
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