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PHYSIOLOGY
103


take place on their surfaces. Thus, a preliminary absorption of the components of a reaction occurs preparatory to the actual chemical change. Whether this increased concentration or close approximation by molecular forces is in itself sufficient to account for the effects or whether there is an intermediate compound formed between the material of the surface of the enzyme and the sub- stances to be acted upon is not yet clear. No such compound has been prepared, but its existence may be so brief as to elude detec- tion. It is evident, however, that the chemical nature of the surface of the enzyme particles may be held responsible for the variety of limited and special activities met with amongst these substances. At the same time, it is not to be forgotten that the physical proper- ties of this surface depend on its chemical nature. In this connexion the views of Langmuir on the orientation of molecules in surface layers may be referred to. In regions of molecular forces, no valid distinction can be drawn between chemical and physical forces.

Much discussion has taken place as to whether enzymes have synthetic as well as hydrolytic powers. In the majority of cases we are dealing 'with undoubted reversible reactions, which attain an equilibrium position other than complete change in either direction. But the two opposite reactions which determine the equilibrium point proceed naturally at a very slow rate. If an enzyme were to accelerate one of these without the other, the equilibrium position would consist in practically complete change in one direction. If this position as reached under the action of an enzyme is anywhere but at the extreme in one or the other sense, it follows that the en- zyme has quickened both the hydrolytic and the synthetic reactions. Many cases of this kind are now known. The actual position of the equilibrium depends on the concentration of water in the system. Thus, in order that the synthetic activity may be pre- ponderant, arrangements are required by which this concentration of free water may be decreased. This may be effected in the cell by colloidal imbibition by absorption on surfaces, or by osmotic ac- tion. If the products of synthesis are rapidly removed either by being deposited in an insoluble form, as for example starch or gly- cogen are, or by being carried away in the blood stream, the syn- thetic process may be continuous, since equilibrium is not reached.

Oxidation. As is well known, the living organism is able to burn food materials, such as glucose, fat and so on, which are only oxidized with such extreme slowness by atmospheric oxygen that combustion appears to be absent in many cases. The mechanism by which oxidation is effected in the organism consists in making use by enzymes of products of oxidation of certain materials which are attacked by atmospheric oxygen. Although details of the mechanism are not altogether clear, the main facts are as follows. When a substance, such as an unsaturated fat or lecithin, is oxidized by oxygen as it exists in the air, it is said to undergo autoxidation. In this process, pari passu with the formation of the ordinary oxide, which of course affords available energy, a peroxide is formed by the aid of this energy. It appears also from Mrs. Onslow's work that the autoxidation may be hastened by an enzyme, thus afford- ing a larger supply of the peroxide. But while a peroxide in itself has greater oxidizing power than oxygen in the molecular state has, or in other words its oxidation potential is higher, this potential is not sufficiently high to attack glucose or lactic acid. If, however, a small amount of a ferrous salt be added, a catalytic separation of oxygen in an " active " state occurs and such refractory materials as lactic acid are then oxidized (Fenton's reaction). Whether ac- tive oxygen is atomic or whether it is in the process of changing its valency, as Ramsay used to teach, is uncertain. The important fact is that we find in living organisms an enzyme, " peroxidase," capable of acting on peroxides in the same way as the iron in Fenton's reaction. Indeed, it seems likely that either iron or nanganese is the responsible constituent of the enzyme.

Oxidation or reduction may also be brought about by substances vhich remove hydrogen from water, thus leaving reactive oxygen. Vs Hopkins has shown, a sulphur group (S-S) may take up hydrogen o form HS-SH, while this compound in its turn may hand on hydrogen to an " acceptor," and so reduce it.

Integration. Organisms behave as coordinated systems, not as ollections of separate cells. There must accordingly be means of nter-communication between all parts. In the animal, the most obvious of these is the nervous system, which makes its appearance at a very early stage of evolution. It may be compared to the telephone system of a city, by which any part can be connected up with any other. This comparison is in many ways an instructive one. Any one subscriber can be put into communication with any other and his line is a " final common path " for messages from various sources. Thus, the nerve supplying any particular muscle is made use of in many various movements, since it can be connected up in the brain with different nerves conveying their respective messages from the sense-organs.

Details of researches on the activities of the central nervous system are beyond the scope of this article. In general it may be said that the conception of a series of alternative parallel arcs at different levels in the hierarchy has shown itself an illuminating one. When the higher arcs come into use, those of lower levels fall into disuse and become relatively resistant to the passage of im- pulses. These lower arcs still remain potentially active and when the higher parts are removed gradually become functional again, to

a greater or less degree. In some cases, their activity is kept in check by the higher arcs and liable to become more or less excessive when the influence of these is removed. Such " release " phenom- ena play an important part in the manifestations of the nerve centres, especially in abnormal states.

Pavlov's method of " conditioned reflexes," by which physio- logical, objective, research on the cerebral cortex can be made, has already led to many valuable results. The part played by inhibi- tory processes has been shown to be a very important one.

As animals grow in size and complexity, some system analogous to that of mechanical transport by roads or railways becomes necessary. Oxygen has to be conveyed to all parts of the body from the place in which it is obtained from the air. The carbon dioxide and other products of chemical change require removal for the purpose of elimination by the organs devoted to this purpose. Food has to be taken from the alimentary canal to other organs in which it is burned or used for repair. As is well known, it is by means of the blood flowing in a voluminous network of tubes that this aspect of integration is effected. Thus, materials in quantity are carried from one organ to another. As regards oxygen and carbon dioxide, further remarks will be found below.

Much attention has naturally been given to the pump, known as the heart, which serves to keep the blood flowing through the vascular system. The most important recent work is that of Star- ling embodied in the Law of the Heart. It was found that all the responses of this organ to the demands of the circulation, apart from the effects of nervous reflexes upon it, could be explained on the basis of a certain property common to all muscle. This prop- erty, which was clearly brought out by the work of A. V. Hill, is that the magnitude of any given contractile effort depends on the length of the fibres when the contraction begins. Hence, the more blood enters the heart during rest the greater is the force expelling it in the next following beat. The property of muscle referred to shows that the source of the contractile stress must be sought in certain surfaces arranged longitudinally or in the direction of the pull exerted. (For recent work on the capillaries, see SHOCK.)

But the system of mechanical transport of a town serves to carry letters in addition to materials for actual use as such. The chemical substance of these letters is not utilized, but they contain messages by which a supply of something or other is ordered to be sent from its source to a place where it is wanted. The so-called " internal secretions," " chemical messengers " or " hormones " correspond to the letters of the postal system. These are produced in some organ and carried by the blood to other situations in which they set various processes into activity. Thus, for example, adrenaline is sent out from the suprarenal glands into the blood. Reaching the liver, it causes a supply of glucose to be set free and supplied to the body generally. It has, of course, other actions as well. We know many of these chemical messengers at the present time. They are formed in the thyroid, pituitary, pancreas, sex-glands and so on. In one or two cases their chemical nature is known, but for the most part this is not yet the case. It seems very probable that every tissue in the organism has its influence on other tissues. In the culture of tissues under the microscope, a method of investigation which has now reached much perfection, it is found that the growth and differentiation of one kind of tissue is greatly influenced by the presence of other tissues.

In the higher plants, this effect of one part upon another is well shown by the inhibitory effect of the apical growing tip upon the growth of other buds. The work of Child suggests that this effect is of the nature of a protoplasmic transmission of some influence rather than the diffusion of an actual inhibiting hormone, as was supposed by the previous workers.

Carriage of Oxygen and Carbon Dioxide. Although it has been known for some time that it is the haemoglobin of the red corpus- cles that carries oxygen from the lungs to the rest of the body, there is still much to learn about the mode in which this gas is attached to the haemoglobin. There are some puzzling phenomena, not the least of which is the fact that we know of no other chemical com- pound that takes up and gives off oxygen in a way similar to that of haemoglobin. In particular, one which combines with oxygen in proportion to the pressure of the gas up to a saturation point which appears, in the case of the blood pigment, to correspond with one molecule of oxygen to each molecule of haemoglobin. Much valuable work has been done on the relationship referred to, es- pecially by Barcroft and his coadjutors, more especially on the way in which it is affected by changes in the conditions present in the blood and tissues. The problem is one of paramount impor- tance in the life of the higher organisms.

The problem of the carriage of carbon dioxide is in a more dis- puted state. While some hold that it is effected by the proteins of the blood actingas acids and driving off carbon dioxide from sodium bicarbonate when the tension of carbon dioxide is lowered, others hold that this gas is carried by haemoglobin in the same way in which oxygen is carried. The decision necessitates difficult measure- ments and is still uncertain.

Regulation of Reaction. Whether the sodium bicarbonate of the blood acts as a carrier of carbon dioxide or not, there is no doubt that it has an important function in preserving the neutrality of the blood. As would be expected from the fact that the various chem-