T I l E UTILIZATION O F SIMPLE DERIVATIVES O F GLUCOSE
BY MOUSE SARCOMA
OVID 0. MEYER, CLAIRE McTIERNAN,
AND
WILLIAM T. SALTER
(prom tks Laboratories of the Collia P. Euntingtm Memorial Hoepita2 o f Haward University)
The researches of Warburg and his colleagues (1) on the metabolism of tumor called attention to the importance of glycolysis in the
life of actively growing tissues, more particularly of malignant tissues, The conditions under which this phenomenon occurs and the
extent to which lactic acid may be produced has been the theme of
numerous papers. A s a by-product of this investigative activity the
notion has become current that there may be something peculiar or
distinctive about the carbohydrate metabolism of tumors. The purpose of the work here reported was to determine whether malignant
tissue metabolizes carbohydrate in a fashion fundamentally different
from that of normal tissues.
C-Atom
3
4
H.C.I08
H.d.38
.G
.
5
6
nAld&ydetl Vyr&nosen ttFuranoaen PrbgsForm
Form
hein's
FIQ.1. FOUR
STRUCTURAL
TYPEBOF Q L U C O ~ E
In the last two the hydrogen and hydroxyl groups have been omitted.
A Romewhat analogous investigation was made by Herring, Irvine,
cziid Macleod ( 2 ) , who concerned themselves with the ability of glucosc
derivat,ives to alleviate the symptoms characteristic of iiisulin hypoglycemia. The plan of the work here reported was to determine what
alterations in the molecular constitution of glucose influence its breakdown (glycolysis) by surviving tumor. The experiments were designed primarily to determine whether the specificity in glycolysis corresponded with the effect on insulin hypoglycemia and with extant
work on isolated muscle or minced muscle.
As regards tumor tistwe, Warburg, Posener, and Negelein ( 3 ) ,
pointed out that glycolysis was rather strikingly limited to hexoses,
arid that in this category only mannose showed a rate of glycolysis of
the same order as glucose: fructose and galactose being less rapidly
1
This work was made possible by a grant from the Ella Sachs Plotc Foundation.
76
UTILIZATION O F GLUCOSE BY MOUSE SARCOMA
77
attacked. The fact, however, as Warburg showed, that about as much
lactic acid was formed from methylglyoxal as from glucose, suggested
that the intracellular enzyme system involved in glycolysis might not
he specific for hexoses per se, but for a characteristic chemical configuration involving not more than three carbon atoms. Kozawa (4),
indeed, has shown that many glucose derivatives penetrate into living
cells. Sjollema and Seekles ( 5 ) , moreover, have emphasized the
toxicity of trioses. Their production in the cell from substituted
glucose, therefore, might conceivably influence the metabolic rate of
the cell# in which glycolysis is marked. Our observations, therefore,
were estended to include not only hexoses but also carbohydrates containing less than six carbon atoms.
RECENT
ADVANCES
IN THE CHEMISTRY
OF CARBOHYDRATES
Irvine (2) has described in detail the chemical configuration of
many of the derivatives of glucose available for biological use. I n
order to avoid needless repetition, the present paper mentions only the
location of the oxygen bridge in the glucose molecule.
Following the epoch-making researches of Emil Fischer, well summarized in Armstrong’s monograph on the carbohydrates ( 6 ) , the
constitution of dextrose was represented by a straight-chain formula.
This “aldehyde” formula f o r d-glucose was later modified by addition
of an oxygen bridge. Although the question is not yet settled, it seems
most convenient to regard normal glucose (as isolated) as the 1,5
amylene-oxide (pyranose) form. It is likely, however, that glucose as
found in chemical combination in nature may exist as the 1,4 butyleneoxide (furanose) form. Pringsheim, moreover, has described a form
of glucose with a 1,6 hexylene-oxide ring ( 7 ) . These are represented
in Fig. 1.
The evidence f o r the existence of these “gamma” forms has been
recently reviewed by Irvine (8) and by I-laworth (9). I n the past
decade, numerous attempts have been made to ascribe to the gamma
forms an important physiological rSle. It has heen suggested that
glucose exists in some such form in the organism, reverting to the 1,s
ring only when isolated.
EXPERIMENTAL
PROCEDURE
The glycolysis of tumor tissiie (mouse sarcoma 180) was determined
by the manometric method of Otto Warburg (1). This transplanted
neoplasm carried in pure strain, tumor-susceptible mice (inbred f o r
nine years) was used throughout. Each mouse was killed when the
implanted tumor was two to four weeks old and the tumor immediately
placed in Ringer’s solution. Ten C.C. of Ringer’s solution, containing
0.20 per cent of sodium bicarbonate and 0.15 per cent of glucose (or
its molecular equivalent of the sugar t o he tested) was previously
prepared. After shaking for twenty minutes in order to permit stahi-
78
DVTD 0. MEYER, CLAIRE MCTIERNAN, AND WILLIAM T. SALTER
lization, the first reading was taken; and thereafter the pressure change
was read every ten minutes for one hour, or until consecutive readiiigs
f o r two or more periods showed similar changes. Usually, an hour
was a sufficiently long period. The pressure change produced by the
(110, evolved was read f o r the given period, and the actual quantity
in cubic millimeters measured by taking into account the constant value
of the closed chamber, determined by previous mercury calibration.
The calculation of the CO, produced per milligram of tissue per
hour was made according to Warburg’s procedure (1). The glycolytic
This designates
index so calculated is represented by the sign Q&
the cubic millimeters of CQ, produced anaerobically per milligram
of tissue per hour, I n many duplicate experiments the difference in
results has been less than 10 per cent. We believe that a glycolytic
index less than 10 per cent that of the glucose control is probably not
sigiiificant.
I n preparing the Ringer’s solution containing an unknown sugar,
f o r comparison with the splitting of glucose, due consideration was
taken of the respective molecular weights, so that equimolecular
equivalents of glucose and unknown sugar were used in the control
and test chambers, respectively. In the case of pentoses and tetroses,
only one equivalent was used. I n the case of trioses, however, two
molecules were used for each molecule of glucose.
The chemical substances were free from glucose as f a r as could be
reasonably ascertained. Two or more of the following criteria
were used to control purity and concentration : reducing power (before
and after hydrolysis), fermentation by yeast, melting point, optical
rotation, and analysis f o r nitrogen or sulphur.
Some of the carbohydrates were purchased from Eastman Kodak
Co. and Pfanstiehl Chemical Go., a few were generously contributed by
academic laboratories,’ and the rest were synthesized in this laboratory.
PBODUCTION
OF ACIDBY MALIGNANT
TISSUEWITH INADEQUATE
OXYGEN
SUPPLY
I n Table I, the substances studied have been arranged, as f a r as
possible, on the basis of, first, the number of carbon atoms which they
contain and, secondly, the position of the group substituted.
Values are given not only for Qgh,, but also for the percentage
which this represents of the acid-production by the control experiment
in which glucose was utilized. The glycolytic index given in each caRe
represents the average of values obtained from two or more experiments. The splitting of abnormal carbohydrates by different specimens of tumor varies to a marked degree, as contrasted with glucose,
which is decomposed at a much more uniform rate in successive experi2 We are indehtecl to Professor W. L. Evans of the University of Illinois, for glyceric
aldehyde; to Dr. P. A. Levene of the Rockefeller Institute, for 3-methyl glucose; to Professor
Reid Hunt of the Harvtlrd Medical School, for propyleiie glycol (1, 2 dihydroxy-propane) ; ant1
to Dr. I. M. Rabinowitch of the Montreal General Hospital, for dihydroxyacetone.
79
UTILIZATTON OF QTJTTCOBE BP MOTWE EARCOMA
TABLE
I
Type of
Substance
Conipouncl,
No. of
b:xpcriments
Av.
@c
Av. per
Av.
:ent COz
Glucose
on basis
Y
i f glucose
2)*
____
Two Carbon Atoms
Triose-deriva t.ivea
Tetrose-derivatives
Pentose-derivat,ives
Ethylene glycol
Et.hyl alcohol
2
3
1.0
2.3
22.4
22.8
4
10
Dihydroxy acetone
Pyruvic acid
Glyceraldehgde
Propglene glycol
Glycerine
Acetone
Proprionic acid
Propyl alcohol
4
2
2
3
2
4
2
4
11.6
4.2
5.2
2.1
1.6
4.0
0.3
3.2
23.3
15.0
16.5
21.0
17.5
23.3
19.0
20.2
50
28
32
9
9
17
2
16
Erythritol
n-Butyl alcohol
Iso-butyl alcohol
Iso-butraldehyde
2
2
3
3
2.6
1
1.2
1.7
17.1
23.3
23.3
23.3
15
4
5
7
d. Xylose
Rhamnose
Arabinose
2
2
3
0
1.7
0.8
14.9
22.9
19.5
0
7
4
3
0
23.6
0
4.2
1.1
3.8
2.1
6.5
27.0
23.4
24.6
22.1
26.9
I6
5
15
10
24
20.6
2.7
3.0
2.0
2.7
19.8
22.5
22.5
19.1
21.8
100
7.2
19.8
36
13
3.0
18.3
2
4
3
2
2.9
1.o
4.3
2.5
20.4
18.4
23.3
21.5
Diacetone glucose
Monoacetone glucose
2
4
1.0
5.3
16.7
22.4
6
24
Glucose acetone carbonate
Glucose monocarbonate
4
2
7.0
1.9
22.5
18.0
35
11
4
3
3.3
1.7
23.2
16.9
14
10
Hexose-derivatives :
Pringsheim glucose,
1-6
Pyranose :
C-&om No. 1
Alpha methyl d-glucoside
d-Sorbitol
d-Gluconic acid
Ethyl d-glucoside
Glucothiose
C-at,om No. 2
d-Mannose
cl-Mannitol
Glucosone
Glucosamine
&Fructose
C-at,om No. 3
S-Met,hyl glucose
C-at,om No. 4
d-Galactose
C-atom No. 6
Furanose:
Acetonecompounds
Carbonates
d-Glycuronic acid
Menthol d-glycuronic acid
Saccharic acid
d-Gulonic acid
2
3
13
3
2
___
12
13
10
12
--
10
14
5
18
12
---
~~~
Anhydrides of glucose Alpha glucosan
Lev0 glucosan
(Toble continued on p . 80)
80
ovin
0. MEYER, CLAIRE MCTIERNAN, AND WILLIAM
T. SALTER
TABLEI (Continued)
Type of
Hubstance
No. of
Expod- ~ v~ .
ments
Compound
Av.
g hGliwose
~
0%
Av. per
cent 2‘ ‘
on basin
of glucose
Dimccharides
Maltose
Cellobiose
Lactose
Sucrose
Trehalose
4
2
2
2
3
2.6
3.5
0.7
2.1
3.5
17.6
24.8
15.7
18.6
22.6
14
14
4
11
16
Trinaccharides
Rafinose
Melezitose
2
2
0.7
2.0
26.7
18.9
3
11
6
5
3
4.0
15.8
1.1
22.1
18.9
15.9
18
84
7
4
0.7
18.6
4
Polysaccharides
Dextrin, crystdine
Starch (soluble)
, Mouse glycogen
Ringer’s (plain)
I
Average of Glucose Experiments.. . , . . . . . . . . . .
4 . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . , . . . , , .20.8
ments. This erratic decomposition is illustrated, for 3-methyl glucose,
by Table 11, in which are listed the glycolytic indices for repeated
experiments with the abnormal sugar against the glucose control value
in each instance. As will appear below, the duration of glycolysis may
be concerned in this phenomenon. Our quotients were obtained mainly
during the first hour.
TAELB11: Showing that a Svbatitiiled Sugar I s More Erratically Glycolyzeil than Glucose Itself
-
3-Methyl Glucose
Glucose Control
Tumor
Number
No. 1
No. 2
No. 3
No. 4
No. 5
Average
Percentage maximum variation
Qgba,
18.2
21.0
19.2
21.0
19.2
Variation
from average
Qgba,
- 7.6%
+ 0.6
- 2.5
+ 6.6
- 2.5
14%
1
13.1
8.0
5.9
5.2
3.7
Variation
from average
++- 82%
11
18
- 28
- 40
7.2
131%
As regards the values for hexose derivatives in Table I, the results
serve to extend further the observation by Warburg as to the specificity of the glycolytic process. Outstanding among these results are
the values for glucose and mannose, which are essentially identical.
Aside from these are a few which give a significant glycolytic index,
i.e. glucothiose, 3-methyl glucose, glucose acetone carbonate, and possihly monoacetone glucose. I n the last two instances, it is conceivable
that the CO, produced is due, directly o r indirectly, to the substituting
81
UTILIZATION OF GLUCOSE BY MOUSE SARCOMA
group rather than to the main molecule. It is at least interesting that
no phenomenal utilization was observed for the 1,6-glucose or for 1,4
derivatives. This result is hardly in accord with the conception that
6 6 gamma” sugars are of physiological importance in mammalian carbohydrate metabolism. It indicates that the position of the oxygen
bridge in glucose is important in its anaerobic breakdown. The anhydrides of glucose-characterized by accessory oxygen bridges in the
molecule-were not utilized to a significant degree. The splitting of
saccharides, likewise, was small. The sole notable exception was soluble starch.
The question arises whether glycolysis of abnormal sugars might be
low because the glycolytic products, into which the sugar is broken, are
toxic and inhibit the process. That the abnormal fragments ( i e . not
simple lactic acid) resulting from breakdown of the substances studied
do not immediately check glycolysis is apparent from Table 111. In
TABLE
111: Anaerobic Glgcolytic Index of Tumor Tissue in the Presence qf Two Sugars
Sugar Combination
Glucose
Control
Concentration
Glucose
)G = (0.075%)
2G = (0.3%)
Glucose plus 3-methyl
glucose
tG
fM(0.075 0.075%)
G = (0.15%) M t(0.15)
3-methy1 glucose
Mf
+
=
+
+
(0.15%)
Q3*
Per cent
Referred
to Glucose
Control
15.6
20.2
22.3
16.3
70 %
125
17.3
22.7
24.1
16.3
72
130
7.2
10.8
36
* Control glucose concentration, designated G = 0.15 per cent.
t M indicates concentration of 3-methyl glucose equivalent to G.
these experiments, equimolecular mixtures of glucose and abnormal
sugar (3-methyl glucose) were compared with solutions containing
half or twice the usual amount of glucose. As will be noted, the
Q&, resulting when equal parts of glucose and 3-methyl glucose
are used approaches the figure obtained when an equivalent concentration of glucose alone is present. The &Fa, seemed to be increased in one case when 3-methyl glucose was added to the usual
amount of glucose. I n the case where %methyl glucose was added t o
a solution containing one-half the usual glucose concentration, that is
0.075 per cent instead of 0.15 per cent, the result approximates that
where 0.075 per cent of glucose alone is used. Thus, in neither instance has inhibition of normal glycolysis resulted from adding 3methyl glucose to the glucose-Ringer’s solution. I n fact, the indices
tend to be additive with respect to the sugar concentrations involved.
EFFECT
OF TIMEON QLYCOLYTIC QUOTIENT
When glycolysis is followed over prolonged periods, the glycolytic
index alters. This is shown in Figure 2 for the case of 3-methyl
glucose. When %methyl glucose alone is given to the tumor, the
82
OVID 0. MEYER, CLAIRE MCTIERNAN, AND WILLIAM T. SALTER
glycolytic rate is not only low but drops off markedly as time progresses. During the seventh hour, indeed, the quotient is only 21 per
cent that of the first hour. Similarly, in sixty-minute experiments
0 Glucose
El Glucose i3-Methyl Glucose
H 3-Methyl Glucwe
No Added Caibohydrate
1
0
PIG.
2.
i
2
3
4 5 6 7
Time in Hours
8
9
10
DIAGRAM SIIOWING ORAPIiICALLY T H E RELATIVE
DEOREE
OF TUMOB
GLYCOLYEISOVER
(1) GLIII'OBE, ( 2 ) 3-METHYL GLUCOSE, ( 3 ) COM~INATION
OF BOTH,AND ( 4 ) RINGER'SSOLUTION
WITHOUT RUC+AR
LOi%(iI'EHIODS FOR
Tho amounts of tissue used wcre smaller than usual and tho rosults higher for each preparation than averagc. However, the rolationships are approxiniately proportional to the averago
results obtainod in other experiments. Each column starts from the baso line 0. Tho relatively slight degreo of glycolysis with 3-methyl glucose a8 compared t o tho persistent high
rato for glucose to tho end is also shown. Each column represents ono hour in time: thue,
xeven hours for the first group; three hours for the eecond; with a half-hour interval while
the manometers wcre dismounted and fresh solutions were exhibited.
with glucothiose the glycolytic rate falls off markedly after the first
lei1 o r twenty miiiutcis.3 Nevertheless, with glucose the rate after seven
hours is iicurly 80 per ceiit of the initial rate.
111 tlic cspcrimeiit tlcpictcd by Fig, 2 the respective tissues were
3 It lllllNt lir rrtiirtnbercd tiint n twcnty-inillute period f o r stubilizntion (of tcwprriituro
mid pressure) procedes the initial manometric reading. This interval prevents measurenient
of very early glyeolysis.
83
UTILIZATION OF GLUUOLJE BY MOUSE SABCOMA
removed from the apparatns at the end of seven hours, and transferred
to fresh solutions. During this process they were, of course, in contact with room air for a short time. Glycolysis again proceeded at a
high rate for the first hour in all cases. The tumor in 3-methyl glucose,
however, again quickly decreased its glycolytic activity to a low level,
whereas the tumor in glucose solution continued, for the entire three
hours, to maintain glycolysis at a level closely approximating the first
period.
It might be possible that free methanol (originating from 3-methyl
glucose by hydrolysis) could have checked glycolysis in this instance.
This possibility was suggested to us by Dr. C. C. Lund. It was excluded, however, by adding in other experiments appropriate amounts
of this alcohol to glucose solutions. The results showed only slight
diminution from the normal glycolytic rate. The inhibiting effect must
be attributed, therefore, to some phenomenon closely connected with
the chemical structure of the substituted sugar, and not to split products originating outside of the cell. A similar possibility that sulphide
might arise from glucothiose and inhibit glycolysis suggested that
sodium sulphide (alone) should be added to the glucose solution.
When this WBB done, however, the glycolytic quotient remained normal.
EFFECT
OF IODOACETATE
AND CYANIDE
It has been shown by Lundsgaard (10) that iodoacetate in small
concentrations stops the splitting of glucose in isolated tissues. We
wished to observe whether jts effect upon other sugars was similar.
We found, as shown in Table IV, that glycolysis for mannose, as well
as glucose, was stopped by this substance. Utilization of the other
substances Was inhibited to a certain degree but not completely. This
result indicates a similarity between trioses and hexoses, when acted
upon by tumor tissue.
TABLEIV: Effect of Iodoacelde ur Cyanide on Glywlysia
~
Compound
Control
from
Table
I
Io!?
"OoSN
20.8
20.6
7.2
11.6
6.2
No%al
1
-___-
Glucoee
Mannose
%methyl glucose
Dihydroxy acetone
G1ycaraldehyde
1I
1.7
1.6
1.3
7.9
2.6
1 Perofcent I
Per cent
from
T+le
1
7
7
19
68
48
I Perofcent
Iodo- Normal Cyanide Normal
acetate
0.001N
from
from
0.0006N Table
Table
I
I
____--1.8
1.9
1.2
9.1
2.4
9
9
17
78
46
22.6
22.0
3.0
3.4
1.7
109
107
42
29
33
Warbnrg (1)has shown that cyanide, 1: 1000 in concentration, does
not inhihit the splitting of glucose by malignant tumors. When compared with the results given in Table I, the quotients in Table IV show
that cyanide does not significantly affect the anaerobic production of
84
OVID 0. MEYER, CLAIRE MCTIERNAN, AND WILLIAM T. SAL!I!ER
carbon dioxide by saraoma in the case of any of the substituted sugarg,
except dihydroxyacetone.
EFFECT
OF NORMAL
TISSUEON ABNORMAL
CARBOHTDRATES
Warburg (1)pointed out that, as regards glucose, tumor tissue differed from resting normal tissue in its high anaerobic glycolysis. Our
experience with mannose and 3-methyl glucose is similar. I n the case
of trioses, however, anaerobic acid-production may appear to be nearly
tis marked for normal tissue (for example, liver) as for tumor tissue.
This is illustrated by Table V, in which the glycolytic quotients for
liver with dihydroxy acetone, propylene glycol, and glyceric aldehyde
ttpproach the analogous values for tumors. Part of this glycolysix,
however, probably represents the breakdown of the carbohydrate already present in the tissue. Indeed, when the corresponding Ringer
control value is subtracted in each case, only the figures for dihydroxy
acetone remain impressive. I n this instance it is noteworthy that the
production of carbon dioxide by liver is much greater than with glucose.
For this fact we have no explanation.
TABLE
V: Action of Surviving @ver Tksue on Triosea ; Apparent Acid-Production Compared with
that of Tumor
Cont,rol Plain
Ringer‘s Holution
-_
Liver
-
-
QE&
2.5
Less Ringer
Control
Tumor
Qzh,
0.7
Dihydroxy
Acetone
Propylene
Glycol
Glyceric
Aldehyde
Control 0.16%
Glucose
Tumor
Liver
Tumor
Liver
Tumor
Liver
Q&
@!ha,
Q%,
QC”,
Q%,
Q&
Q:ht,
11.2
11.6
4.3
2.1
2.7
5.2
2.5
20.8
8.7
10.9
1.8
1.4
0.2
4.5
0
20.1
Liver
Tumor
G?),
-
DISCU66ION
If one compares our results with those of Laquer and Meyer (111,
obtained with minced muscle, one finds the two series in close accord.
(The outstanding discrepancy is offered by fructose.) Blix (12) used
Ahlgren’s (13) method to determine how various sugars influenced thc?
reduction of methylene blue by surviving frog muscle. Blix likewise
found this phenomenon to be highly specific for glucose.
As far as intact animals are concerned, the results of Herring,
Irvine, and Macleod (2) with insulin hypoglycemia were complicated
by the transformation of some compounds into glucose by the liver.
In general, however, they demonstrated the marked specificity of glucose per se as an antidote for insulin. Using hepatectomized animals,
1)rury and Salter (14) found that without the intervention of the liver,
most glucose derivatives are useless for the other organs. This was a8
true of the accredited carbohydrate “intermediates ” as of the other
substances studied.
UTILIZATION OF ULUUOSE BY MOUSE SARCOMA
85
This study of the glycolytic breakdown of various carbohydrates by
tumor tissue shows the same sugars and intermediaries t o be glycolyzed
as are utilized by normal tissues. I n short, the utilization of carbohydrates by malignant tissue does not differ qualitatively from their
utilization by normal tissues. This fact suggests that the anomalous
oarbohydrate metabolism of malignant tissue may be merely a difference in degree, rather than in kind.
Although the negative results obtained with many of these glucose
derivatives may be interpreted as evidence of enzyme specificity, due
allowance must be made for the possibility that cell membranes may
be impermeable to such abnormal sugars. Indeed, Harrison and Mellanby (15) found malignant tissue unable to glycolyze hexose phosphate
in vitro. Yet there is good ground (16) for believing that hexose phosphate plays an essential r61e in glycolysis within the cell. It is obvious
then that a negative result may mean simply that the sugar in question
cannot penetrate the cell membrane. This situation ’has been shown by
Scharles and Salter (17) to hold for glycogen, the molecule of which is
of colloidal dimensions. There is an amylase within tumor cells which
splits the polysaccharide. Nevertheless, until the cell membranes are
destroyed, the glycogen in the Ringer ’8 solution remains untouched, as
may be seen from Table I.
It is by no means certain that the acid produced from these abnormal Carbohydrates is exclusively or necessarily lactic acid. I n
certain instances, notably 3-methyl glucose, it seems probable that part
of the acid evolved is a substituted lactic acid, derived from one-half
of the substituted glucose molecule. I n other cases, e.g. glyceric aldehyde, it is possible that decarboxylation may be the mechanism involved. Even so, such reactions have a fundamental physiologic
significance because, as Salter and Robb have found (18),they influence
nitrogenous metabolism in tumor,
SUMMARY
In studying differences between the biochemical behavior of malignant tissue (mouse sarcoma 180) and that of normal tissues, the utilization of various derivatives of glucose (in which successive chemical
groups were systematically substituted) was measured under anaerobic
conditions by Warburg’s method. Barring differential permeability
of those substances through cell membranes, and similar complications,
such compounds may be considered as substrates, the chemical change
in which gives quantitative evidence of the activity of intracellular
enzymes.
The splitting of hexoses (“glycolysis”) is peculiarly restricted to
d-glucose itself, the chief exception being mannose, as Warburg pointed
out. Of various simple derivatives of glucose, most failed to show
much acid-formation. That the configuration of the oxygen ring is of
prime importance is indicated by the fact that Pringsheim’s glucose
(hexylene-oxide ring) showed no glycolysis. Glucofuranose compounds (butylene-oxide ring), however, were encountered, which did
86
OVID 0. MEYER, CLAIRE MCTIERNAN, AND WILLIAM T. BALTEB
yield acid under anaerobic conditions, though not so readily as normal
dextrose.
Although no anaerobic acid-formation was eiicountered with pentoses, it was definite in the case of several 3-carbon aliphatic carbohydrates. This process is inhibited by iodoacetate, but not markedly by
cyanide. Acid produotion from these substances by rapidly growing
tumor, however, may be little greater than by normal tissue (liver).
Acid production of only slight degree was observed in the case of
saccharides containing glucose.
The persistence of great acid production from glucose, over long
periods, stands in contrast to the relatively small production from 3methyl glucose after two to three hours.
CONCLUSIONS
A study of the glycolytic breakdown of various carbohydrates by
tumor tissue shows the same sugars to be glycolyzed as are utilized by
normal tissues.
The anomalous carbohydrate metabolism of malignant tissue is a
difference in degree rather than in kind.
BIBLIOQRAPHY
1. WARBURQ,
0. : fiber den Stoffwechsel der Tumoren, Berlin, Julius Springer, 1926.
Eng. trans., The Metabolism of Tumors, by Frank Dickens, New York, Richard
R. Smith, Inc., 1931.
2. HERRING),
P. T., IRVINE,
J. C., AND MACLEOD,
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