The carbohydrate of the food, having been converted into monosaccharides in the intestine, is taken up by the capillary blood vessels of the intestinal wall and passes from them into the portal vein. After a meal rich in carbohydrate the blood of the portal vein is rich in glucose, sometimes reaching twice its normal glucose content; and may show levulose and galactose as well. In the blood of the general circulation, however, only glucose is found, and this remains small in quantity -about one tenth of one per cent - even after a meal rich in carbohydrates, so that a considerable part of the carbohydrate taken must be stored temporarily in the liver and given up gradually to the blood in the form of glucose, thus keeping nearly constant the glucose content of the blood of the general circulation. The carbohydrate thus stored in the liver cells is deposited in the form of glycogen, which, after an abundant meal, may reach 10 per cent of the weight of the liver (or, in rare cases, an even higher figure) and may fall to nearly nothing when no carbohydrate food has been taken for some time. To a less extent the muscles store glycogen in a similar way, their glycogen contents varying from traces to about 2 per cent.

The fact that the carbohydrate stored in the liver after a meal is so largely converted into glucose and passes into the blood current before the next meal, while the glucose content of the blood remains small and nearly constant, indicates that the glucose of the blood must be quite rapidly used, and from our present standpoint the most important question of the carbohydrate metabolism is the fate of the glucose carried to the muscles and other tissues by the blood.

Oxidation Of Carbohydrate

By comparison of the arterial and venous blood, it is plain that in its passage through the muscles the blood becomes poorer in glucose and oxygen and richer in carbon dioxide, and this change is more marked when the muscle is active than when it is at rest. The oxidation of glucose in the muscles is in some way dependent upon the pancreas, but the exact function of the pancreas in this connection is still obscure. It is not to be supposed that the glucose is burned directly to carbon dioxide and water. There is much evidence that the glucose molecule is broken before oxidation, and in all probability this first cleavage yields mainly three-carbon compounds.

Some lactic acid is always produced by working muscle and this has long been regarded as a possible intermediate product in the metabolism of glucose.* Lactic acid appears to bear important relationships both to carbohydrate metabolism and to muscle contraction. The discussion of the significance and role of lactic acid cannot be attempted here. It may be said, however, that in recent years much experimental evidence has accumulated in support of the view that lactic acid is not formed directly from glucose, but rather through the intervention of other three-carbon compounds, probably glyceric aldehyde or methyl glyoxal (pyruvic aldehyde) or both.

* It should perhaps be noted here that lactic acid plays a part not only in the metabolism of carbohydrate but of other foodstuffs as well. It may be formed, for instance, from glycerol and from certain amino acids.

If we think of the glucose molecule as first breaking into three-carbon molecules with a minimum of internal rearrangement, the most probable primary product would appear to be glyceric aldehyde, the formation of which might be represented crudely as follows:

CH2OH • CHOH CHO|H • CHOH • CHOH • CHO

Or, to write the reaction in a more usual form, C6H12O6 →2 CH2OH • CHOH • CHO

Glucose Glyceric aldehyde.

It is also possible that the first product of cleavage of glucose may be pyruvic aldehyde or methyl glyoxal:

C6H12O6→2 CH3 • CO • CHO + 2H2O

Glucose Methyl glyoxal (Pyruvic aldehyde).

Both glyceric aldehyde and methyl glyoxal have been shown to result from the cleavage of glucose under the influence of alkali in vitro and there are doubtless enzymes in the tissues which catalyze one or both of these reactions with the result that glucose readily undergoes such cleavage as a preliminary to oxidation in the body.

Opinion is at present divided as to whether glyceric aldehyde or pyruvic aldehyde (methyl glyoxal) is to be regarded as the usual first step in glucose metabolism. In either case it is probable that the bulk of the carbohydrate material passes through the form of pyruvic aldehyde (methyl glyoxal) on its way to oxidation.

According as we assume the process to go on with or without the intermediary formation of glyceric aldehyde, the production of lactic acid from glucose in the body may be represented in either of the following ways:

C6H12O6 -> CH2OH • CHOH • CHO -> CH3 • CO • CHO

Glucose Glyceric aldehyde Pyruvic aldehyde.

→CH3 • CHOH • COOH

Lactic acid or:

C6H12O6 → CH3 • CO • CHO→ CH3CHOH • COOH

Glucose Pyruvic aldehyde Lactic acid.

Each of these reactions has been brought about in the laboratory by heating with alkali and at the lower alkalinity of the body the tissue enzymes are believed to catalyze the same or similar changes. Moreover it has been shown that under suitable experimental conditions lactic acid is formed from glyceric aldehyde and from pyruvic aldehyde by the action of surviving liver tissue; and the further fact that in experimental diabetes glucose may be formed from glyceric or pyruvic aldehyde as well as from lactic acid tends also to confirm the belief that these aldehydes are intermediary products between glucose and lactic acid - both in normal metabolism and experimental diabetes. Glycerol also when perfused through liver tissue yields lactic acid, and since the first product of oxidation of glycerol is in all probability glyceric aldehyde, we have here a further reason for believing that the latter is a normal precursor of lactic acid. There has been no direct demonstration of the presence of glyceric aldehyde or of pyruvic aldehyde (methyl glyoxal) in the body; but this is probably due to their unstable or highly reactive nature. The view that glyceric aldehyde passes through pyruvic aldehyde in being transformed into lactic acid is not only probable on stereochemical grounds but is strongly supported by much recent evidence indicating that pyruvic aldehyde occupies a central position in the intermediary metabolism.