THE BIOCHEMICAL RELATION BETWEEN PYRUVIC ACID AND GLUCOSE.

BY H. D. DAKIN AND N. W. JANNEY.

(From the Herter Laboratory and the Chemical Laboratory of the MonteJiore Home, New York.)

(Received for publication, June 1, 1913.)

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 Mayer’s 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 con- sumption 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 publica- tion of Mayer’s second paper, lead to an entirely different con- clusion. Moreover, we have learned from conversation with Dr. Ringer that he has obtained results essentially similar to ours. By mutual arrangement Dr. Ringer’s results appear simultane- ously 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 adminis- tration 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

1 Biochem. Zeitschr., xlix, p. 486, 1913. 2 Ibid., xl, p. 441, 1912.

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178 Glucose Formation from Pyruvic Acid

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 poly- merization 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 reduc- tion 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 connec- tion 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:

CHa CO I COOH red”ctio~ CHa. CHOH . COOH __f CHa. CO. CHO - CsHlzOs Pyruvic acid Lactic acid Methyl glyoxal 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 pre- vious publications. The phlorhizin was given suspended in olive oil according to Coolen’s 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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H. D. Dakin and N. W. Janney ‘79

EXP.

I

II

III

EXP.

IV

ERICJI

I II

III v, v

VI VII

I II

III IV V

I II

III IV

GLUCOBE : --

NITROom

11.42 3.48 19.53 3.38

9.81 3.15 16.56 3.21 12.15 3.08

25.38 7.83 27.03 7.83 25.07 6.43 25.91 7.60 29.92 7.29

28.19 8.93 32.15 8.12 27.52 8.82 26.29 8.91

II 8.28 III 5.73 IV 7.12 V 21.30

VI 21.20 VII 5.72

VIII 5.92 IX 20.37

X 18.55 XI 12.75

I- I I’ 4.39

NITROGEN

11.56 12.25

9.90 10.43 11.72 15.34 10.97 10.22 9.37 8.11

11.52

G:N

3.28 3.31 5.78 3.11 5.16) 3.94)

3.24 3.45 3.88 3.41 4.14

3.16 3.96 3.12 2.95

13.2 16.8 16.1 17.7 17.0 19.7 17.9 17.7 17.9 16.3 18.4

8.75 / 12.5 gms. pyruvic acid.

8.46 10.7 gms. lactic acid.

3.40 12 gms. pyruvic acid.

5.35 ‘12 gms. pyruvic acid.

6.65 i 10 gms. pyruvic acid.

0 115 gms. polymerized pyruvic acid.

:4 gms. pyruvic acid in 5 portions.

17 gms. lactic acid 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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180 Glucose Formation from Pyruvic Acid

grams of pyruvic acid appears to give 3.4 grams of ‘(extra glucose,” while the same amount 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. Multi- ple 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 excre- tion 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 con- sumption of sodium pyruvate (28 grams) and sodium lactate (5.3 grams). The analyses show little of interest and are not reproduced.

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H. D. Dakin and N. W. JanneyGLUCOSE

BETWEEN PYRUVIC ACID AND THE BIOCHEMICAL RELATION

1913, 15:177-180.J. Biol. Chem. 

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