THE

BIOCHEMICAL
ACID
BY H. D.

(From

the Herter

Laboratory

(Received

RELATION
BETWEEN
AND GLUCOSE.

DAKIN

AND N.

W. JANNEY.

and the Chemical

Home,
New York.)
for

publication,

PYRUVIC

Laboratory

June

of the MonteJiore

1, 1913.)

1 Biochem.
Zeitschr.,
xlix,
2 Ibid., xl, p. 441, 1912.

p. 486,

1913.
177

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In a recent communication
by Paul Mayer1 an unsuccessful
attempt was made to demonstrate glucose synthesis from pyruvic
acid in phlorhizinized
animals.
These negative results were the
more surprising on account of Paul Mayers earlier inve6tigations2
upon the effect and fate of pyruvic acid in the animal body:
In
these experiments it was shown in the most convincing fashion
that glucose may be excreted in the urine on administering pyruvic
acid to rabbits, that this effect is accompanied by hyperglycaemia,
and finally that glycogen synthesis could be shown to follow consumption of pyruvic acid by previously starved rabbits.
As a result of his negative experiments Paul Mayer is inclined
to the belief that a definite proof of the formation of glucose from
pyruvic acid cannot be furnished by the use of glycosuric animals.
Our own experiments, which were completed before the publication of Mayers second paper, lead to an entirely different conclusion.
Moreover, we have learned from conversation with Dr.
Ringer that he has obtained results essentially similar to ours.
By mutual arrangement
Dr. Ringers results appear simultaneously with our own (p. 145).
We find that the sodium salt of pyruvic acid given by mouth
to diabetic animals under suitable conditions may give rise to
almost as large an excretion of extra glucose as does administration of lactic acid itself.
In these experiments we have used
dogs treated with phlorhizin and also human diabetics.
When
sodium pyruvate
is administered
subcutaneously
to glycosuric

178

Glucose

Formation

from

Pyruvic

Acid

CHa CO I COOH redctio~ CHa. CHOH . COOH __f

Pyruvic acid
Lactic acid

CHa. CO. CHO Methyl glyoxal

CsHlzOs
Glucose

If the experimental conditions do not favor the initial reduction

of pyruvic acid to lactic acid, it is probable that no synthesis of
glucose can follow.
The experimental results are contained in the following tables.
The general conditions were similar to those described in previous publications. The phlorhizin was given suspended in olive
oil according to Coolens method. In every case the excretion
of acetoacetic acid and P-hydroxybutyric acid was followed, but
no increase was observed to follow the administration of pyruvic
acid. The figures are therefore omitted.

a This Journd, xiv, p. 555, 1913.

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dogs, especially to small animals, a definite but relatively small

increase in extra
glucose
is noted. Incidentally
we have
observed that pyruvic acid which has undergone extensive polymerization on long standing may yield little or no glucose. It
is therefore important
for these experiments
that the acid be
freshly distilled before use.
A consideration of our results together with those of Paul Mayer
leads us to the belief that glucose cannot be formed directly from
pyruvic acid but that if the conditions are favorable for the reduction of the latter substance to lactic acid, then glucose may be
produced.
Such a hypothesis would harmonize with our observed
experimental data and would be in entire accord with a hypothesis
concerning glucose formation recently put forward by one of us
in conjunction with Dudley.3
It should be noted in this connection that Mayer has actually detected inactive lactic acid in the
urine of normal rabbits receiving sodium pyruvate, and it is now
known that both d- and Z-lactic acids and methyl glyoxal may
lead to the synthesis of glucose.
Our idea of the relationship between pyruvic acid and glucose
may be gathered from the following scheme:

H. D. Dakin and N. W. Janney

EXP.

III

GLUCOBE

NITROom

G:N

I
II
III
v, v
VI
VII

11.42
19.53
9.81
16.56
12.15

3.48
3.38
3.15
3.21
3.08

3.28
3.31
5.78
3.11
5.16)
3.94)

I
II
III
IV
V

25.38
27.03
25.07
25.91
29.92

7.83
7.83
6.43
7.60
7.29

3.24
3.45
3.88
3.41
4.14

28.19
32.15
27.52
26.29

8.93
8.12
8.82
8.91

3.16
3.96
3.12
2.95

II
III
IV

EXP.

8.75

/ 12.5 gms.

pyruvic

8.46

10.7 gms.

lactic

3.40

12 gms.

acid.
acid.

pyruvic

acid.

5.35

12 gms. pyruvic

acid.

6.65

i 10 gms.

acid.

pyruvic

115 gms. polymerized

pyruvic
acid.

NITROGEN

IV

:
--

II
III
IV
V
VI
VII
VIII
IX
X
XI

4.39
8.28
5.73
7.12
21.30
21.20
5.72
5.92
20.37
18.55
12.75

II 11.56
12.25
9.90
10.43
11.72
15.34
10.97
10.22
9.37
8.11
11.52

13.2
16.8
16.1
17.7
17.0
19.7
17.9
17.7
17.9
16.3
18.4

:4 gms. pyruvic

17 gms.

lactic

acid

acid

in 5 portions.

in 7 portions.

EXPERIMENT I. Dog weighing

12 kgms.
Sodium
pyruvate
and lactate
given by stomach
tube.
Urine collected
in g-hour periods.
Using G : N =
3.22 it may be calculated
that 12.5 grams
of pyruvic
acid gave 8.75 grams
extra
glucose,
while 10.7 grams lactic acid gave 8.46 grams.
EXPERIMENT II.
Bitch
weighing
8 kgms.
Urine
collected
in la-hour
periods.
Sodium
pyruvate
given subcutaneously
in period
II, by mouth,
in period
V.
Using G : N = 3.37, the subcutaneous
administration
of 12

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II

ERICJI

79

180

Glucose

Formation

from

Pyruvic

Acid

grams of pyruvic
the same amount

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acid appears
to give 3.4 grams of (extra
glucose,
while
given by mouth
yielded
5.35 grams.
EXPERIMENT III.
Dog weighing
19 kgms.
10 grams of pyruvic
acid as
sodium
salt given by mouth
gave 6.65 grams of extra
glucose.
15 grams
of polymerized
pyruvic
acid given
subcutaneously
led to no additional
glucose
excretion.
EXPERIMENT IV. Female.
Moderate
case of diabetes
mellitus.
Multiple sclerosis
and slight
tubercular
involvement
of right
pulmonary
apex.
During
a preliminary
period
of nine days when the total
carbohydrate
consumption
averaged
80 grams per day, the average
daily glucose
excretion was 32 grams.
A large increase
in glucose
excretion
is seen to follow
the administration
of both sodium
pyruvate
and lactate.
EXPERIMENT V. A mild case of diabetes mellitus;
similar
to the above.
Only
a trifling
increase
(2-7 grams)
in glucose
excretion
followed
the consumption
of sodium
pyruvate
(28 grams)
and sodium
lactate
(5.3 grams).
The analyses
show little
of interest
and are not reproduced.

THE BIOCHEMICAL RELATION

BETWEEN PYRUVIC ACID AND
GLUCOSE
H. D. Dakin and N. W. Janney
J. Biol. Chem. 1913, 15:177-180.

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