ADENINE DERIVATIVES AND THEIR BIOLOGICAL FUNCTIONS
Authors: LUTWAK‐MANN CECILIA 
Published: January 2008

Adenine derivatives represent a group of substances of considerable biological interest. Our knowledge of their occurrence in nature, properties and role is derived from both chemical and biological investigations.

With regard to chemical structure, they fall into three groups of different complexity: (I) the comparatively simple molecules adenosine, adenylic acid, adenyl pyrophosphoric acid, (2) the intermediate compounds di‐adenosine‐penta‐phosphoric and di‐adenosine‐tetraphosphoric acid, and (3) the dinucleotides cozy‐mase, Warburg's coenzyme, amino‐acid oxidase coenzyme, which apart from adenine possess yet another base (pyridine, alloxazine).

Adenosine does not occur in free state in nature. It can be obtained by hydrolysis from yeast nucleic acid. Adenosine is a substance of potent physiological activity, especially on the heart. Deamination of adenosine to inosine (e.g. by enzymes present in many tissues and body fluids) renders this substance phydogically inactive.

Adenylic acid (adenine nucleotide) is a general cell constituent. With regard to chemical structure we distinguish between muscle and yeast adenylic acid, the phosphoric group in the former being attached to C5, in the latter to C3, of the ribose molecule. Accordingly these two substances differ in several aspects, both chemical and biological. It is the muscle adenylic structure which is met with in the rest of the higher adenine derivatives.

Adenylic acid occurs in tissues and cells in the form of adenyl pyrophosphoric acid and only seldom in free state (heart muscle). The pyrophosphoric group is easily split off, enzymically or by acid hydrolysis. A method is described for quantitative determination of adenyl pyrophosphoric and adenylic acid in biological material.

In addition to adenylic and adenyl pyrophosphoric acid there exist other poly‐phosphoric adenine derivatives, such as the di‐adenosine‐pentaphosphoric acid in heart muscle and the di‐adenosine‐tetraphosphoric acid in yeast.

Cozymase, diphosphopyridine nucleotide, originally called “coenzyme of alcoholic fermentation”, is a substance of wide distribution in nature. Owing to the presence of the pyridine ring (nicotinic acid amide) in its molecule, it can undergo reversible oxidation and reduction: cozymasezdihydrocozymase. In the enzymic oxido‐reduction systems (dehydrogenases) where it acts as coenzyme it plays the part of a hydrogen carrier, transferring the hydrogen from the substrate to a hydrogen acceptor such as flavoprotein.

Warburg's coenzyme, triphosphopyridine nucleotide, was first isolated from red blood cells and later found to occur in many other cells. Structurally it is closely related to cozymase, but it possesses one more phosphoric acid group than cozymase. The mechanism of its action as hydrogen carrier in enzyme systems is identical to that of cozymase, but in purified enzyme preparations these two coen‐zymes cannot replace each other in spite of their close similarity. There is some evidence, however, that cozymase and Warburg's coenzyme are to a certain degree interconvertibIe under the influence of cell extracts.

Alloxazine‐adenine nucleotide is a substance of ubiquitous presence in biological material. Originally isolated from heart muscle and kidney as the coenzyme of the amino‐acid oxidase, it was soon found to be essential for other enzymic proteins as well (flavoprotein, xanthine oxidase). Its role as hydrogen carrier is due to the reversible oxidation and reduction of the alloxazine ring.

The function of the adenine derivatives in biological processes, e.g. phosphate transfer by the adenylic system and hydrogen transfer by cozymase, is discussed in muscle glycolysis and alcoholic fermentation. Coupling is shown to occur between the phosphorylations and oxido‐reductions in some of the intermediary stages of glycolysis and fermentation.

Enzyme systems are quoted in which the two pyridine dinucleotides and the alloxazine dinucleotide act as coenzymes.