Chemical reactions in metabolism. Eva Samcová Petr Tůma

Transcription

1 Chemical reactions in metabolism Eva Samcová Petr Tůma

2 METABOLISM Living organisms are not at equilibrium. They require a continuous influx of free energy. Overall process through which living systems acquire and utilize free energy to carry out their various functions. They do so by coupling the exergonic reactions of nutrient oxidation to the endergonic processes required to maintain the living state (for mechanical work, active transport of molecules, biosynthesis of complex molecules and so on)

3 Metabolic pathways Metabolic pathways are irreversible a highly exergonic reaction (having large negative free energy change) is irreversible (makes the entire pathway irreversible) Catabolic and anabolic pathways must differ Every metabolic pathway has a first commited step metabolic pathways are irreversible but most reactions in pathway are close to equilibrium. Early in each pathway is irreversible reaction that commits the intermediate it produces to continue down the pathway Commited step All metabolic pathways are regulated usually by enzymes that catalyze their first committed step (often rate-limiting step) Metabolic pathways in eucaryotic cells occur in specific cellular locations

4 Major Fuel Metabolism Pathways

5 Metabolism of saccharides, lipids and proteins Krebs cycle nutrients CO 2 + H 2 O + energy Connection through carboxylic acids pyruvate lactate citrate oxaloacetate malate succinate fumarate

6 Chemical reaction for repeating Esterification Formation of Schiff bases Aldol condensation

7 Esterification

8 Imine (Schiff base) formation

9 Aldol condensation

10 Disociation of acid Carboxylic acids Resonant structure acid acidum anion acyl methanoic formic formicum methanoate formate formyl ethanoic acetic aceticum ethanoate acetate acetyl propanoic propionic propionicum propanoate propionate propionyl butanoic butyric butyricum butanoate butyrate butyryl ethanedioic oxalic oxalicum oxalate oxalyl propanedioic malonic malonicum malonate malonyl butanedioic succinic succinicum succinate sukcinyl pentanedioic glutaric glutaricum glutarate glutaryl

11 Significant carboxylic acids in metabolism CH 3 CH COOH CH 3 C COOH OH 2-hydroxypropanoic acid = lactic acid = lactate O 2-ketopropanoic acid = pyruvic acid = pyruvate x enolpyruvate HOOC CH 2 CH COOH OH Malic acid (hydroxybutanedioic acid) = malate Oxaloacetic acid (oxobutanedioic acid) = oxalacetate succinic acid (butanedioic acid) = succinate Fumaric acid (butenedioic acid) = fumarate

12 Significant carboxylic acids in OH metabolism CH 2 C CH 2 COOH COOH COOH Citric acid = citrate x isocitrate Malonic acid (propanedioic acid) = malonate 2-ketoglutaric acid (2- oxopentanedioic acid) = 2- ketoglutarate Acetoacetic acid (3- oxobutanoic acid) = acetoacetate 3-hydroxybutyric acid = 3-hydroxybutyrate

13 Transformation of amino acids to keto acids Amino acids CO 2 + H 2 O + NH 3 Transamination AA 1 + OxoA 2 OxoA 1 + AA 2 alanine + 2-oxoglutarate pyruvate + glutamate aspartate + 2-oxoglutarate oxaloacetate + glutamate Oxidative deamination glutamate 2-oxoglutarate + NH 3 Urea synthesis CO 2 + 2NH 3 urea

14 Decarboxylation and carboxylation Decarboxylation Elimination of CO 2 Amino acids biogenic amines glutamate GABA 5-hydroxytryptophan serotonin histidine histamine Carboxylation acetyl-coa malonyl- CoA Synthesis of fatty acids

15 H 2 as a source of energy and dehydrogenation 2H 2 + O 2 2H 2 O + energy Dehydrogenation 1. Oxidation of single bond to double bond -CH 2 -CH 2 - -CH=CH- + 2H + + 2e - β-oxidation of fatty acids succinate fumarate desaturation synthesis of unsaturated fatty acids 2. Dehydrogenation of 2-keto acids pyruvate acetyl-coa + CO 2 + 2H + + 2e - 2-ketoglutarate succinyl-coa + CO 2 + 2H + + 2e -

16 Dehydrogenation (oxidation) of alcohols Metabolism of ethanol Poisoning by methanol and ethylene glycol

17 Hydrolysis Hydrolysis of saccharides - glycosidases Hydrolysis of proteins - peptidases Hydrolysis of lipids - lipases

18 Reactions of monosaccharides Glucuronic acid gluconolactone. glukonová glucitol glucose-6-phosphate fructose mannose α-methylglucoside

19 Phosphoryl Group Transfer Potentials & Phosphate Hydrolysis

20 Endergonic Reactions Coupled to ATP Hydrolysis

21 Metabolic Functions of Eukaryotic Organelles