Historical opinion: Erwin Chargaff and his 'rules' for the base composition of DNA: why did he fail to see the possibility of complementarity?

Erwin Chargaff was one of the more interesting and colourful figures of the historic decade that heralded the proposal of the double helical structure of DNA by Watson and Crick in 1953. In describing Chargaff's important contribution to the study of DNA, particularly its base composition, this article seeks to suggest why, despite his substantial achievements, he failed to anticipate some of the key features of the Watson-Crick model, particularly complementarity between bases--a failure that left him deeply embittered for the rest of his life.

The crystallization of enzymes and virus proteins: laying to rest the colloidal concept of living systems.

In 1946 three Americans shared the Nobel Prize for Chemistry--James Sumner 'for his discovery that enzymes can be crystallized', and John Northrop and Wendell Stanley 'for their preparation of enzymes and virus proteins in a pure form'. The award made history as the first time that the Chemistry Prize was shared by three individuals. It also doubled the number of Americans that had received the Chemistry award since its inception in 1901.

Determination of the kinetics of guanine nucleotide exchange on EF-Tu and EF-Ts: continuing uncertainties.

An analysis is made of the rate constants for the reactions involving the interactions of EF-Tu, EF-Ts, GDP, and GTP recently derived by Gromadski et al. [Biochemistry 41 (2002) 162]. Though their measured values appear to allow a reasonable rate of nucleotide exchange sufficient to support rates of protein synthesis in vivo, their data underestimate the thermodynamic barrier involved in nucleotide exchange and therefore cannot be considered definitive. A kinetic scheme consistent with the thermodynamic barrier can be achieved by modification of various rate constants, particularly of those involving the release of EF-Ts from EF-Tu.GTP.EF-Ts, but such constants are markedly different from what are experimentally observed. It thus remains impossible at present satisfactorily to model guanine nucleotide exchange on EF-Tu, catalysed by EF-Ts by a double displacement mechanism, with experimentally derived rate constants. Metabolic control analysis has been applied to determine the degree of flux control of the different steps in the pathway.

Man of destiny: the life and work of Fritz Haber.

'The German physical chemist Fritz Haber was distinguished not only for his researches, but also for his services to industry and to his country. Haber and the research institutes he directed contributed to a wide range of advances in physical chemistry. His most outstanding scientific achievement was his synthesis of ammonia, which solved the urgent problem of meeting the world demand for nitrogen fertiliser'. So begins the entry to Haber in the 1972 Encyclopaedia Britannica. Haber was indeed a great and versatile scientist, but his was also a vigorous and complex personality that interacted in unexpected ways with the social and political circumstances of his time.

The mechanism by which insulin controls protein synthesis

Insulin, as well controlling sugar metabolism controls protein synthesis in several tissues. When isolated muscle is incubated with a radio-active amino acid the presence of insulin increases the amount of radio-activity incorporated into protein. Although this observation implies that insulin is enhancing the cativity of the machinery for protein synthesis in the cell, there have always been lingering doubts about this conclusion because of the problem of knowing how much dilution of its radio-activity the amino acid undergoes on entry into the cell before its incorporation into protein, and whether this process is affected differently in the presence of insulin. It has now proved possible to study protein synthesis in a cell-free system isolated from muscle after incubation, with or without insulin. In this system the activity of the soluble fraction of the cell, which activates the amino acids before their incorporation into protein, is increased by the hormone. In addition the ability of the ribosomal fraction to incorporate amino acids into protein is also enhanced. Thus the increase in incorporation of amino acids into protein seen with insulin with the intact tissue is due at least in part to increase in the activity of the protein synthesising machinery, visible at least two stages. How insulin may bring about this result will be discussed (AU)

Hormonal and nutritional control of protein synthesis in muscle - abstract

The rate of protein synthesis in muscle is controlled by amongst other things insulin. In diabetes and fasting the rate of synthesis is lower than normal and is raised by administration of the hormone. The effect of insulin registers in several ways - it increases the ability to the tissue to take up certain though apparently not all amino acids and it increases the proportion of the cell's complement of ribosomes that are contained in polysomes through attachment to messenger RNA. Supply of amino acids has been shown for some cells to be a potent factor in promoting polysome formation. It is thus possible that the action of insulin to promote amino acid uptake is the means by which it controls the entry of ribosomes into polysomes. Against this must be set the fact that the levels of free amino acids in muscle tend to remain relatively constant in the various deficiencies mentioned. That this should be so suggests the existence of a mechanism which regulate rates of protein synthesis and breakdown to a degree such that constant pool sizes are maintained - this despite the fact that amino acid catabolism itself increases with endocrine and nutritional deficiency. It is hoped to enlarge on some of these problems (AU)

Effect of insulin on protein synthesis

The mechanism by which insulin controls protein metabolism is not fully understood. Insulin stimulates protein synthesis; it also enhances transport of some amino acids, but the latter action does not appear to be sufficient explanation of the increase in synthesis. The various actions seem to be independent of the effects of glucose metabolism. In diabetic muscle there are a fewer than normal polysomes, and insulin rapidly enhances attachment of monomers to messenger-RNA. Insulin also increases the effectiveness of cell sap in catalyzing protein synthesis by ribosomal systems. The way in which the hormone may affect either initiation or peptide synthesis is not known. Experiments are reported bearing on whether availability of amino acids could be a mechanism by which effects of insulin are mediated. Activity of liver and muscle soluble fractions declines on fasting and, for the latter tissue, possibly also on a low protein diet. Sap from fasting animals allows a much smaller response of isolated ribosomes to added amino acids. Availability of glutamate in amino acid mixtures may be of special importance. However, insulin can influence the activity of the sap fraction of diaphram muscle during incubation without the presence of amino acids in the medium. Understanding of what mechanisms are involved will depend on resolution of the critical sap factors (Summary)