L. A. Walford

Bio: L. A. Walford is an academic researcher. The author has contributed to research in topics: Bioenergetics. The author has an hindex of 1, co-authored 1 publications receiving 2972 citations.

Cellular energy utilization and molecular origin of standard metabolic rate in mammals

Abstract: The molecular origin of standard metabolic rate and thermogenesis in mammals is examined. It is pointed out that there are important differences and distinctions between the cellular reactions that 1) couple to oxygen consumption, 2) uncouple metabolism, 3) hydrolyze ATP, 4) control metabolic rate, 5) regulate metabolic rate, 6) produce heat, and 7) dissipate free energy. The quantitative contribution of different cellular reactions to these processes is assessed in mammals. We estimate that approximately 90% of mammalian oxygen consumption in the standard state is mitochondrial, of which approximately 20% is uncoupled by the mitochondrial proton leak and 80% is coupled to ATP synthesis. The consequences of the significant contribution of proton leak to standard metabolic rate for tissue P-to-O ratio, heat production, and free energy dissipation by oxidative phosphorylation and the estimated contribution of ATP-consuming processes to tissue oxygen consumption rate are discussed. Of the 80% of oxygen consumption coupled to ATP synthesis, approximately 25-30% is used by protein synthesis, 19-28% by the Na(+)-K(+)-ATPase, 4-8% by the Ca2(+)-ATPase, 2-8% by the actinomyosin ATPase, 7-10% by gluconeogenesis, and 3% by ureagenesis, with mRNA synthesis and substrate cycling also making significant contributions. The main cellular reactions that uncouple standard energy metabolism are the Na+, K+, H+, and Ca2+ channels and leaks of cell membranes and protein breakdown. Cellular metabolic rate is controlled by a number of processes including metabolic demand and substrate supply. The differences in standard metabolic rate between animals of different body mass and phylogeny appear to be due to proportionate changes in the whole of energy metabolism. Heat is produced by some reactions and taken up by others but is mainly produced by the reactions of mitochondrial respiration, oxidative phosphorylation, and proton leak on the inner mitochondrial membrane. Free energy is dissipated by all cellular reactions, but the major contributions are by the ATP-utilizing reactions and the uncoupling reactions. The functions and evolutionary significance of standard metabolic rate are discussed.

Regression Using Fractional Polynomials of Continuous Covariates: Parsimonious Parametric Modelling

Abstract: The relationship between a response variable and one or more continuous covariates is often curved. Attempts to represent curvature in single‐ or multiple‐regression models are usually made by means of polynomials of the covariates, typically quadratics. However, low order polynomials offer a limited family of shapes, and high order polynomials may fit poorly at the extreme values of the covariates. We propose an extended family of curves, which we call fractional polynomials, whose power terms are restricted to a small predefined set of integer and non‐integer values. The powers are selected so that conventional polynomials are a subset of the family. Regression models using fractional polynomials of the covariates have appeared in the literature in an ad hoc fashion over a long period; we provide a unified description and a degree of formalization for them. They are shown to have considerable flexibility and are straightforward to fit using standard methods. We suggest an iterative algorithm for covariate selection and model fitting when several covariates are available. We give six examples of the use of fractional polynomial models in three types of regression analysis: normal errors, logistic and Cox regression. The examples all relate to medical data: fetal measurements, immunoglobulin concentrations in children, diabetes in children, infertility in women, myelomatosis (a type of leukaemia) and leg ulcers.

Quantitative Laws in Metabolism and Growth

Abstract: T _ HE work reviewed in this paper is aimed at establishing connections between two fundamental aspects of living organisms, their metabolism and growth. What we call growth of even a simple organism is a tremendously complex phenomenon from the biochemical, physiological, cytological, and morphological viewpoints. There are, however, certain aspects that are amenable to quantitative analysis, and such an approach appears to lead to some insight into the connections between metabolism and growth, and to some answer to the seemingly trivial, but in fact hardly explored question, \"Why does an organism grow at all, and why, after a certain time, does its growth come to a stop?\

6 – Physiological Energetics

Abstract: Fish, like other living systems, must conform to the laws of thermodynamics. Fish gain matter and energy in food, and they lose absorbed matter and energy as a result of catabolism—which provides energy for maintenance and activity—and the elaboration of reproductive products. Physiological energetics, or animal bioenergetics, concerns the rates of energy expenditure, the losses and gains, and the efficiencies of energy transformation, as functional relations of the whole organism. The majority of such presentations commence with an energy-flow diagram indicating the main steps that the energy of food intake follows through the organism, and the paths of energy distribution. Each of these steps with their appropriate values is subject to quantitative change, depending on many biotic and abiotic factors. With the thought that the basis of these energy exchanges needs to be elaborated first, it was deemed more fitting to conclude with a quantitatively expressed flow diagram. An understanding of the physical, chemical, and biological basis on which the energetics is built, and the equivalents employed, constitutes the opening section of this chapter. Some necessary distinctions between mammalian and nonmammalian systems are made. An adequately nutritious diet is assumed; the basic source of fuel for the fire of life is solely derived from the food.