The Chemistry of Metabolism Chapter 19 The Chemistry of Metabolism
Introduction We have now studied the typical reactions of the major classes of organic compounds and the structure and reactions of carbohydrates, nucleic acids, and lipids We now apply this background to the study of the organic chemistry of metabolism glycolysis -oxidation of fatty acids the citric acid cycle
Metabolism The process by which organisms acquire and use energy to carry out various functions. Organisms are not at equilibrium; they couple reactions that release energy with reactions that require energy. Plants and certain bacteria obtain free energy from the sun; other organisms must obtain energy by oxidizing organic compounds.
Metabolism Metabolic reaction pathways are generally divided into two categories Catabolism: pathways that are involved in breaking down nutrients into small organic molecules, these usually release energy Anabolism: pathways that that are involved in synthesis of larger complex molecules, these usually require energy Catabolism and anabolism are not simply the reverse of each other, they are separate sets of pathways.
Overview of Metabolism
Digestion Enzymes break down complex macromolecules:
Digestion Breakdown of smaller molecules:
Anabolism Biosynthesis of macromolecules:
Anabolism Biosynthesis of macromolecules:
Five Key Participants Five compounds participating in these and a great many other metabolic pathways: ATP, ADP, and AMP are universal carriers of phosphate groups NAD+/NADH and FAD/FADH2 are coenzymes involved in oxidation/reduction of metabolic intermediates; they are universal transporters of electrons Coenzyme: a low-molecular-weight, nonprotein molecule or ion that binds reversibly to an enzyme, functions as a second substrate, and is regenerated by further reaction
Adenosine Triphosphate (ATP) ATP is the most important of the compounds involved in the transfer of phosphate groups
Adenosine Triphosphate (ATP) Hydrolysis of the terminal phosphate of ATP gives ADP and phosphate in glycolysis, for example, the phosphate acceptors are -OH groups of glucose and fructose
NAD+/NADH Nicotinamide adenine dinucleotide (NAD+) is a biological oxidizing agent
NAD+/NADH when NAD+ acids acts as a biological oxidizing agent, it is reduced to NADH when NADH acts as a biological reducing agent, it is oxidized to NAD+
NAD+/NADH its redox reactions involve transfer of a hydride ion, H:-
FAD/FADH2 Flavin adenine dinucleotide (FAD) is also a biological oxidizing agent
FAD/FADH2 when FAD functions as an oxidizing agent, it is reduced to FADH2
Coenzyme A Coenzyme A (Co-A) is a carrier of acetyl groups as acetyl coenzyme A (acetyl-CoA) the acetyl group is bound to the -SH group as a thioester
Glycolysis Breakdown of glucose – synthesis of pyruvate for citric acid cycle
Glycolysis Reaction 1: Phosphorylation of Glucose
Glycolysis Reaction 2: Isomerization
Glycolysis Reaction 3: Phosphorylation
Glycolysis Reaction 4: Cleavage
Glycolysis Reaction 5: Isomerization
Glycolysis Reaction 6: Oxidation (exothermic)
Glycolysis Reaction 7: Formation of ATP
Glycolysis Reaction 8: Formation of 2-Phosphoglycerate
Glycolysis Reaction 9: Formation of Phosphoenolpyruvate (PEP)
Glycolysis Reaction 10: Formation of ATP
Glycolysis Reaction 10: Formation of ATP Pyruvate reacts with CoASH to make Acetyl-CoA and enters Citric Acid Cycle
Fates of Pyruvate Pyruvate does not accumulate in cells, but rather undergoes one of three enzyme-catalyzed reactions, depending of the type of cell and its state of oxygenation reduction to lactate reduction to ethanol oxidation and decarboxylation to acetyl-CoA A key to understanding the biochemical logic behind two of these fates is to recognize that glycolysis needs a continuing supply of NAD+ if no oxygen is present to reoxidize NADH to NAD+, then another way must be found to do it
Pyruvate to Lactate in vertebrates under anaerobic conditions, the most important pathway for the regeneration of NAD+ is reduction of pyruvate to lactate
Pyruvate to Lactate while lactate fermentation does allow glycolysis to continue, it increases the concentration of lactate and also of H+ in muscle tissue when blood lactate reaches about 0.4 mg/100 mL, muscle tissue becomes almost completely exhausted
Reduction to Ethanol yeasts and several other organisms regenerate NAD+ by this two-step pathway, known as alcoholic fermentation
Oxidation to Acetyl-CoA this conversion requires both thiamine pyrophosphate and lipoic acid
The Citric Acid Cycle
The Citric Acid Cycle Reaction 1: Formation of Citrate
The Citric Acid Cycle Reaction 2: Isomerization to Isocitrate
The Citric Acid Cycle Reaction 3: First Oxidative Decarboxylation
The Citric Acid Cycle Reaction 4: Second Oxidative Decarboxylation
The Citric Acid Cycle Reaction 5: Hydrolysis of Succinyl-CoA
The Citric Acid Cycle Reaction 6: Dehydrogenation of Succinate
The Citric Acid Cycle Reaction 7: Hydration of Fumarate
The Citric Acid Cycle Reaction 8: Dehydrogenation forms Oxaloacetate
Oxidative Phosphorylation NADH and FADH2 produced in Citric Acid Cycle undergo oxidative phosphorylation. Oxygen is reduced to water with the formation of ATP from ADP. One mole of glucose is metabolized to form a net of 36 moles of ATP.
Citric Acid Cycle as seen from the balanced equation for the cycle, it is truly catalytic the intermediates in the cycle are neither synthesized nor destroyed in the net reaction
Oxidation of Fatty Acids There are two major stages in the oxidation of fatty acids activation of the free fatty acid in the cytoplasm and its transport across the inner mitochondrial membrane -oxidation -Oxidation: a series of four enzyme-catalyzed reactions that cleaves carbon atoms two at a time from the carboxyl end of a fatty acid
Activation of Fatty Acids begins in the cytoplasm with formation of a thioester formation of the thioester is coupled with the hydrolysis of ATP to AMP and pyrophosphate
Activation of Fatty Acids activation of a fatty acid involves ATP
Activation of Fatty Acids and then reaction with coenzyme A
-Oxidation Reaction 1: oxidation of a carbon-carbon single bond to a carbon-carbon double bond
-Oxidation Reaction 2: hydration of the carbon-carbon double bond; only the R enantiomer is formed
-Oxidation Reaction 3: oxidation of the -hydroxyl group to a carbonyl group
-Oxidation Reaction 4: cleavage of the carbon chain by a reverse Claisen condensation
-Oxidation Spiral
-Oxidation this series of reactions is then repeated on the shortened fatty acyl chain and continues until the entire fatty acid chain is degraded to acetyl-CoA