Glutamine was first isolated from beet juice in 1883 by Schulze and Bosshard (1), and since that time it has been the subject of continued interest and research. The widespread occurence of this amide in nature, in bath the free and combined state, is consistent with a significant metabolic role, and there is evidence for its participation in a variety of enzymatic reactions.

Miescher, who may be regarded as the founder of the knowledge of the chemistry of the cell nucleus, carried out his initial investigations on isolated pus nuclei obtained from discarded surgical bandages. He showed (1) that the nuclear material contained an unusual phosphorus compound which he called ‘nuclein’, and which we now know to have been nucleoprotein. In later studies, he became interested in salmon sperm as a source of nuclear material, and he found that the isolated sperm heads contained an acidic compound which gave analytical figures for phosphorus, carbon and nitrogen corresponding to what is now known as nucleic acid.

Complex macromolecules, particularly proteins and nucleic acids, occupy a central position in the architecture and functioning of living matter. They are intimately connected with all phases of chemical and physical activity that constitute the life and reproduction of the cell. Yet these enormous molecules are synthesized within the cell from very small simple substances which may be obtained from the diet. As understanding of intermediary metabolism has increased, attention bas become focused upon certain small molecules or radicals, containing one, two or three carbon atoms, which appear repeatedly in various pathways.

Tissues are both morphologically and physiologically divisible into at least two phases. One phase is comprised of either cellular or intracellular material which performs the specific function characteristic of the tissue (for example contraction in the case of the muscle or conduction in the case of nerve). In brain this phase consists of the neurons with its nucleated cell body, axons and dendrites. The other phase is extracellular and contains those anatomic elements and associated fluids essential for the physical support and nutritive maintenance of the cellular phase. In addition there are blood vessels, interstitial fluids, and non nervous connective tissue; the ependyma which lines the ventricles, the neuroglia cella and fibers.

Carbon tetrachloride (tetrachloromethane, CCl4) was discovered in 1839 by the French chemist and physician, H. V. Regnault, as a product of the action of chlorine upon chloroform in sunlight (1). It is almost insoluble in water, but is miscible with chloroform, alcohol, ether and benzene (1, 2, 3). Its non-flammability and low cost are the chief factors combining to make CC14 one of the most widely-used volatile solvents today. Hardin (1) has prepared an interesting review which traces the history of CC14 through its various applications and uses. For approximately 12 years (1865-67), CCl4 had a short and unhappy trial as an anaesthetic, and was proven to be inferior to chloroform in this capacity.

The writer has developed an assay for estimation of optimal hexokinase activity in stroma-free hemolyzate, and shown that hexokinase remains stable and active for at least 30 days in human erythrocytes preserved in CD or ACD at 4 °C. Addition of ADP or DPN to the assay medium could increase the enzyme 1s activity; nicotinamide or alloxan depressed it. It is suggested that failure of glycolytic activity during preservation is not therefore due to the formerly supposed lability of hexokinase, but to inhibition of hexokinase attributable to falling pH and ATP, and conditions favouring glucose-6-P accumulation such as decrease of phosphofructokinase, DPN and ADP. Pyruvate produced in cells during the first 15 days of storage tended to be expelled into the external medium. Cyclic adenylate was utilised by the human red cell, as evidenced by conversion of its ribose moiety into lactic acid with concomitant esterification of inorganic phosphate into the stable phosphate fraction.

Acetylcholine (ACh) is widely accepted as a neurotransmitter substance. The marked physiological activity of this substance could have been suspected from the early pharmacologic studies of Hunt and Taveau who demonstrated its intense depressor activity. Later, Ewins isolated it from specimens of ergot which had depressor action on organs supplied by autonomic nerves. Dale then found that this depressor activity was similar to that of muscarine-like substances and that this effect could be abolished by atropine. The same author also showed that ACh could easily be inactivated by an esterase present in tissue.

Tumour tissues in vitro show an incorporation of glucose carbon into glycine, alanine, glutamate and aspartate. The incorporation into glutamate and aspartate is lower than that observed in normal rat brain cortex slices or chick embryo. This may be due to a lower rate of operation of the citric acid cycle compared with that of glycolysis in tumours. When normal rat brain cortex slices are incubated with tumour tissues in vitro, in a medium containing 5 mM 14 glucose-U-C14, there is a decrease in the amount of glutamine found in the brain cortex slices, with a concomitant increase in the incorporation of glucose carbon into glutamate, aspartate and alanine of the tumour tissues.

The phenomenon of selective permeation of certain substances across tissue membranes and into cells has long been recognized as a function of fundamental and essential importance. The composition of the intracellular fluid is, under normal physiological conditions, quite different from that of the extracellular fluid and it is the role of the external membrane surrounding the cytoplasm of each cell to maintain this state. The mechanisms which come into play in this process are still far from completely understood, although a great deal of work has been devoted to their study.

The principle of natural selection was applied by Darwin to the individual organ as well as to the organism. Each organ may be considered the result of selections through perhaps many millions of generations, arriving at its present level of development and specialization primarily by way of natural selection. The mammalian heart is a striking example of an organ which has evolved to do a specific task with a high degree of efficiency. The primary function of the heart is that of pumping fluid nutritive material to the organism. As this enormous task must be performed continuously throughout the life of the organism, it would be expected that such a function would require a highly versatile and specialized organ.