Iso- and anteiso-fatty acids in bacteria: biosynthesis, function, and taxonomic significance.

Introduction Fundamentals of biochemical modeling Balance equations Rate laws Generalized mass-action kinetics Various enzyme kinetic rate laws Thermodynamic flow-force relationships Power-law approximation Steady states of biochemical networks General considerations Stable and unstable steady states Multiple steady states Metabolic oscillations Background Mathematical conditions for oscillations Glycolytic oscillations Models of intracellular calcium oscillations A simple three-variable model with only monomolecular and bimolecular reactions Possible physiological significance of oscillations Stoichiometric analysis Conservation relations Linear dependencies between the rows of the stoichiometry matrix Non-negative flux vectors Elementary flux modes Thermodynamic aspects A generalized Wegscheider condition Strictly detailed balanced subnetworks Onsager's reciprocity reactions for coupled enyme reactions Time hierarchy in metabolism Time constants The quasi-steady-state approximation The Rapid equilibrium approximation Modal analysis Metabolic control analysis Basic definitions A systematic approach Theorems of metabolic control analysis Summation theorems Connectivity theorems Calculation of control coefficients using the theorems Geometrical interpretation Control analysis of various systems General remarks Elasticity coefficients for specific rate laws Control coefficients for simple hypothetical pathways Unbranched chains A branched system Control of erythrocyte energy metabolism The reaction system Basic model Interplay of ATP production and ATP consumption Glycolytic energy metabolism and osmotic states A simple model of oxidative phosphorylation A three-step model of serine biosynthesis Time-dependent control coefficients Are control coefficients always parameter independent? Posing the problem A system without conserved moieties A system with a conserved moiety A system including dynamic channeling Normalized versus non-normalized coefficients Analysis in terms of variables other than steady-state concentrations and fluxes General analysis Concentration ratios and free-energy-differences as state variables Entropy production as response variable Control of transient times Control of oscillations A second-order approach A quantitative approach to metabolic regulations Co-response coefficients Fluctuations of internal variables versus parameter perturbations Internal response coefficients Rephrasing the basic equations of metabolic control analysis in terms of co-response coefficients and internal response coefficients Control within and between subsystems Modular approach Overall elasticities Overall control coefficients Flux control insusceptibility Control exerted by elementary steps in enzyme catalysis Control analysis of metabolic channeling Comparison of metabolic control analysis and power-law formalism Computational aspects Application of optimization methods and the interrelation with evolution Optimization of the catalytic properties of single enzymes Basic assumptions Optimal values of elementary rate constants Optimal Michaelis constants Optimization of multienzyme systems Maximization of steady-state flux Influence of osmotic constraints and minimization of intermediate concentrations Minimization of transient times Optimal stoichiometries.

The Regulation of Cellular Systems

The lipid composition and biochemistry of freshwater fish.

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and type 2 diabetes. NAFLD represents a large spectrum of diseases ranging from (i) fatty liver (hepatic steatosis); (ii) steatosis with inflammation and necrosis; and (iii) cirrhosis. Although the molecular mechanism leading to the development of hepatic steatosis in the pathogenesis of NAFLD is complex, recent animal models have shown that modulating important enzymes in fatty acid synthesis in liver may be key for the treatment of NAFLD. This review discusses recent advances in the field.

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Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice

Malonyl-coenzyme A (malonyl-CoA), generated by acetyl-CoA carboxylases ACC1 and ACC2, is a key metabolite in the regulation of energy homeostasis. Here, we show that Acc2-/- mutant mice have a normal life span, a higher fatty acid oxidation rate, and lower amounts of fat. In comparison to the wild type, Acc2-deficient mice had 10- and 30-fold lower levels of malonyl-CoA in heart and muscle, respectively. The fatty acid oxidation rate in the soleus muscle of the Acc2-/- mice was 30% higher than that of wild-type mice and was not affected by addition of insulin; however, addition of insulin to the wild-type muscle reduced fatty acid oxidation by 45%. The mutant mice accumulated 50% less fat in their adipose tissue than did wild-type mice. These results raise the possibility that pharmacological manipulation of ACC2 may lead to loss of body fat in the context of normal caloric intake.

https://science.sciencemag.org/content/sci/291/5513/2613.full.pdf

Vasudev C. Joshi

Papers

Fatty Acid Synthesis and Its Regulation

Induction of microsomal stearyl coenzyme a desaturase in newly hatched chicks

Studies on the mechanism of fatty acid synthesis. XXIV. The acetyl- and malonyltransacylase activities of pigeon liver fatty acid synthetase.

Assay for the terminal enzyme of the stearoyl coenzyme A desaturase system using chick embryo liver microsomes.

Hormonal regulation of fatty acid synthetase in chick embryo liver.