Approaches to modelling metabolism past and current Bas
Approaches to modelling metabolism, past and current Bas. Kooijman@vu. nl Brest, 2019/04/1 -12 https: //deb 2019. sciencesconf. org
Contents 1. What is metabolism and its origins 2. Biochemical approaches 3. Pool approaches 4. Historical context 5. Static vs dynamic budgets 2019
Metabolism Transformation of chemical compounds in cells to maintain and propagate life conversion of food/fuel to energy to run cellular processes, conversion of food/fuel to building blocks for proteins, lipids, nucleic acids, and some carbohydrates elimination of nitrogenous wastes. The concept energy was first proposed by Thomas T. Young in 1807 Life originated as prokaryotes metabolism of prokaryotes is basic to metabolism From Wikipedia 2019
2019 Metabolism during evolution Red algae Eukaryotes Anoxygenic photosynthesis Flesh Great Oxidation Event Life Vascular plants Cyanobacteria From: Judson, Nature Ecol & Evol 1, 0138 (2017)
Early ATP generation Fe. S + S 0 Fe. S 2 ADP + Pi ATP • ATPase • hydrogenase • S-reductase Fe. S 2 Fe. S H 2 S 0 H 2 S 2 e. S 0 H 2 S 2 H 2 O 2 OH- 2 H+ ADP Pi 2019 ATP 2 H+ Madigan et al 1997
Central Metabolism 2019 source polymers monomers waste/source
Evolution of central metabolism 2019 in prokaryotes (= bacteria) 3. 8 Ga 2. 7 Ga i = inverse ACS = acetyl-Co. A Synthase pathway RC = Respiratory Chain PP = Pentose Phosphate cycle Gly = Glycolysis TCA = Tri. Carboxylic Acid cycle Kooijman, Hengeveld 2005
2019 Prokaryotic metabolic evolution Heterotrophy: • pentose phosph cycle • glycolysis • respiration chain Phototrophy: • el. transport chain • PS I & PS II • Calvin cycle Chemolithotrophy • acetyl-Co. A pathway • inverse TCA cycle • inverse glycolysis
Symbiogenesis 2. 7 Ga phagocytosis 2. 1 Ga 1. 27 Ga 2019
Evolution of DEB systems 1 strong homeostasis for structure 2 delay of use of internal substrates 3 internalisation of maintenance as demand process increase of maintenance costs 4 5 7 Kooijman & Troost 2007 Biol Rev, 82, 1 -30 reproduction juvenile embryo + adult animals 8 strong homeostasis for reserve installation of maturation program prokaryotes variable structure composition 6 plants 9 specialization of structure
Symbiosis on the basis of syntrophy substrate product
Symbiosis on the basis of syntrophy substrate
Survey of organisms (brown algae) Phaeophyceae Basidiomycota Xanthophyceae Raphidophyceae Ascomycota Chrysophyceae Synurophyceae Actinopoda Zygomycota Eustigmatophyceae Microsporidia Labyrinthulomycota Dictyochophyceae Bicosoecia Pedinellophyceae Chytridiomycota Pelagophyceae Plasmodiophoromycota Pseudofungi Bacillariophyceae Chlorarachnida (diatoms) Opalinata Cercomonada Choanozoa Bolidophyceae Granuloreticulata Xenophyophora animals Apusozoa mitochondria primary chloroplast secondary chloroplast tertiary chloroplast photo symbionts Bacteria Myxomycota Protostelida Archaeprotista Rhizopoda Metamonada Parabasalia Percolozoa Euglenozoa Kinetoplastida Diplonemida Loukozoa Prymnesiophyceae Cryptophyceae Sporozoa Dinozoa Ciliophora (plants) Cormophyta (green algae) Chlorophyceae (red algae) Rhodophyceae Glaucophyceae
Biochemical approaches 2019 Weak: Need for selection of the most important compounds Still many variables and parameters, realism is difficult to test No mass or energy balance Cell environment is highy structured, small number of molecules Time scales of dynamics of molecules vs individual far apart Limited generality Strong: Direct link with molecular biology (gene regulation) Rapid technological progress Large influx of big data
ATP generation & use 5 106 ATP molecules in bacterial cell enough for 2 s of biosynthetic work mean life time of ATP molecule: 0. 3 s Only used if energy generating & energy demanding transformations are at different site/time 2019 If ADP/ATP ratio varies, then rates of generation & use varies, but not necessarily the rates of transformations they drive Processes that are not much faster than cell cycle, should be linked to large slow pools of metabolites, not to small fast pools
Pool approaches 2019 Weak: Complex identification of players of the game if > 1 implication: difficult connection with molecular biology Complex link with genes Weak homeostasis is a simplification of a complex reality Strong: Few players of the game: implication: energy & mass conservation can be exploited Limited range in time and space scales involved Large generality implication: comparison on the basis of parameter values Direct link between flux and function
2019 History of metabolic modelling 1668 John Mayow relates respiration to combustion 1779 A. Crawford measures animal heat production 1780 A. L. Lavoisier & P. S. de Laplace relate heat to O 2 consumption and CO 2, NH 3 production 1805 Thomas T. Young invents concept energy 1839 Sarrus & Rameaux relate O 2 consumption to body size 1865 Alfred R Wallace in a letter to E. B. Poulton: “Supposing organisms ever existed that had not the power of natural reproduction, then the absorptive surface would only increase as the square of the dimensions while the bulk to be nourished and renewed would increase as the cube, there must soon arrive a limit to growth” 1883 M. Rubner invents the 2/3 -law for respiration as function of body weight 1891 Snell makes extensive use of allometric functions 1916 Krogh fits allometric curves to respiration as function of body weight 1920 August Pütter models growth based on surface area and volume 1932 M. Kleiber invents the ¾-law for respiration as function of body weight 1934 Ludwig von Bertlanffy: growth is difference between ana- & cata-bolism 1947 E. Zeuthen: intra- and inter-specific comparisons are different
Pütter vs von Bertalanffy August Pütter, 1920 2019 Ludwig von Bertalanffy, 1938 anabolism catabolism For simplicity: std DEB model at single constant food level std DEB model at different constant food levels
Surface area/volume interactions Membrane-mediated transformation rates in isomorphs decrease with length because of transportation distance 2019 inactive enzyme in binding phase active enzyme in production phase substrate product Cells can “know” their size from the rate at which concentrations of substrate & product change if transformation is by membrane-bound enzymes
Allometric functions 2019 Problems: • No mechanism, thus descriptive • Respiration has additive components (maintenance, growth, sda) this is incompatibe with allometric functions • No natural candidate for Wref and dim(α) = dim(Y) * dim(W)-b
Respiration 2019
Empirical special cases of DEB year author model 1780 Lavoisier multiple regression of heat against mineral fluxes 1950 Emerson cube root growth of bacterial colonies 1825 Gompertz 1891 Survival probability for aging DEB theory is axiomatic, 1951 Huggett & Widdas temperature dependence of Arrhenius 1951 Weibull based on mechanisms physiological rates allometric growth of body parts Huxleynot meant 1955 Best to glue empirical models 1902 Henri 1905 Blackman 1889 1910 1920 Michaelis--Menten kinetics 1957 Smith foetal growth survival probability for aging diffusion limitation of uptake embryonic respiration bilinear functional response 1959 Leudeking & Piret microbial product formation Since many empirical models Cooperative binding hyperbolic functional response Hill 1959 Holling turn out to be special cases of DEB theory von Bertalanffy growth of maintenance in yields of biomass Pütter 1962 Marr & Pirt individuals the data behind these models support DEB theory 1927 Pearl logistic population growth 1973 Droop reserve (cell quota) dynamics 1928 Fisher & Tippitt Weibull aging 1974 Rahn & Ar water loss in bird eggs 1932 Kleiber respiration scales with body weight 3/ 4 1975 Hungate digestion 1932 Mayneord cube root growth of tumours 1977 Beer & Anderson development of salmonid embryos This makes DEB theory very well tested against data
Static Energy Budgets (SEBs) Numbers: k. J in 28 d C energy from food A assimilation energy P production (growth) F energy in faeces U energy in urine R respiration (heat) From: Brafield, A. E. and Llewellyn, M. J. 1982 Animal energetics, Blackie, Glasgow
Static Energy Budgets (SEBs) SEBs are net production models gross ingested Losses are first subtracted from incoming resources, rest is allocated to various endpoints faeces apparent assimilated SEBs are single-pool models urine No metabolic memory or condition index No embryos gross metabolised spec dynamic action Problems in application maintenance = respiration production overheads? respiration & urine linked to current food intake somatic no Kleiber net metabolised maintenance thermo regulation production work activity growth products reproduction
Empirical patterns 1 From Sousa et al 2008 Phil. Trans. R. Soc. Lond. B 363: 2453 -2464
Empirical patterns 2 From Sousa et al 2008 Phil. Trans. R. Soc. Lond. B 363: 2453 -2464
J-first S+J-first E-first kappa-first Topological alternatives for 2 -pool models E reserve X food S som maint J mat maint G growth R reprod/mat Lika & Kooijman 2011 J. Sea Res 66: 381 -391
Test of properties From Lika & Kooijman 2011 J. Sea Res, 66: 381 -391
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