Introduction to Metabolism

Metabolism
(The Acquisition and Utilization of Free Energy)

Catabolism: exergonic oxidation Anabolism: endergonic processes

(Biosynthesis) (Endergonic)

(Exergonic) (Oxidation)

Function of ATP
• Cells make use of ATP for:

• Chemical work – ATP supplies energy to synthesize macromolecules, and therefore the organism • Transport work – ATP supplies energy needed to pump substances across the plasma membrane • Mechanical work – ATP supplies energy for cellular movements

Redox Reactions

NAD (Nicotinamide Adenine Dinucleotide) Electron transfer from NADH provides free energy (NAD+/NADH) H O C + N R N A+ D N H 2  +  2 e +H H H O C N H 2 N R N A DH The electron transfer reaction: NAD+ + 2e + H+  NADH. It may also be written as: NAD+ + 2e + 2H+  NADH + H+ .

FAD (Flavin Adenine Dinucleotide) d i m e t h y l i s o a l l o x a z i n e O H C C 3 H C C 3 H C C C N C C C N H O C C C N H CO 2 e+ 2 HH C 3  + C H C C C H N C H N N CO H C C 3 C H 2 H C O H C H N C H 2 N H H C O H F A D H C O H H C O H O O A d e n i n e F A D H 2 H C O H H C O H O O A d e n i n e H C OP OP OR i b o s e 2 O O - H C OP OP OR i b o s e 2 O O - FAD accepts 2 e + 2 H+ in going to its reduced state: FAD + 2 e + 2 H+  FADH2 .

Metabolic Networks Reactions: Pathways: Networks: A B A B C D A B C E D .

Metabolic Pathways A ——> B .

Metabolic Pathways A ——> B ——> C ——> D ——> E .

Metabolic Pathways A ——> B ——> C ——> D ——> E F ——> G ——> H .

Metabolic Pathways A ——> B ——> C ——> D ——> E e5 e6 e7 e1 e2 e3 e4 F ——> G ——> H .

Metabolic Pathways A ——> B ——> C ——> D ——> E e5 e6 e7 e1 e2 e3 e4 F ——> G ——> H .

Metabolic Pathways S A ——> B ——> C ——> D ——> E e5 e6 e7 e1 e2 e3 e4 F ——> G ——> H Cell membrane P .

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Properties of Metabolic Pathways • Irreversible (overall): reversibility of individual steps • Separate Anabolic and Catabolic Pathways • First Committed (Exergonic) Step: others close to equilibrium • Regulation (usually first committed step): often rate-limiting • Compartamentation: transport .

ATP .Control of Metabolic Pathways • • • • • Feedback inhibition Enzyme modulators No enzyme Enzyme isolation Energy availability .

Example of Metabolic Regulation .

A Summary of the Pathways of Catabolism and Anabolism .

Catabolism: The Breakdown of Macro-nutrients .

Energy Production ATP • Glycolysis – Phosphorylation – Pyruvate • Anaerobic respiration • Lactate production • 2 ATPs produced Overview of aerobic pathways for ATP Production .

Glycolysis Event 1 .Phosphorylation • two phosphates added to glucose • requires ATP Event 2 – Splitting (cleavage) • 6-carbon glucose split into two 3-carbon molecules 4-14 .

Glycolysis Event 3 – Production of NADH and ATP • hydrogen atoms are released • hydrogen atoms bind to NAD+ to produce NADH • NADH delivers hydrogen atoms to electron transport chain if oxygen is available • ADP is phosphorylated to become ATP • two molecules of pyruvic acid are produced 4-15 .

Glycolysis Summary • Inputs: • Glucose • 2 NAD+ • 2 ATP • 4 ADP + 2 P • Outputs: • 2 pyruvate • 2 NADH • 4 ADP • 2 ATP (net gain) .

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Anaerobic Reactions If oxygen is not available • electron transport chain cannot accept NADH •pyruvic acid is converted to lactic acid •glycolysis is inhibited •ATP production declines 4-16 .

the end-product of glycolysis.Fermentation • In the absence of oxygen. pyruvate. When this happens. – During glycolysis. . glycolysis will stop. • 2 NADH and 2 ATP produced. – Pyruvate is used as the electron acceptor resetting the NAD+ for use in glycolysis. is used in fermentation. all the NAD+ becomes saturated with electrons (NADH).

– Alcoholic fermentation . – Muscle fatigue • Yeasts.Fermentation – 2 Types • Animals add extracted electrons to pyruvate forming lactate. single-celled fungi. – Reversible when oxygen becomes available. produce ethanol. – Present in wine & beer.

3-butanediol + formate + lactate + carbon dioxide + hydrogen Lacta te Ethanol + carbon dioxide Propiona te + carbon dioxide + hydrogen + acetate Butyrate + butanol + isopropanol + acetone + carbon dioxide 31 .Pyruvate fermentation Escherichia Enterobacter Lactobacillus Saccharomyces Propioni-bacterium Clostridium Ethanol + lactate + acetate + succinate + carbon dioxide + hydrogen + formate Ethanol + 2.

Glycolysis takes place in the cytoplasm of almost all cells. .

Aerobic Reactions If oxygen is available – • pyruvic acid is used to produce acetyl CoA • citric acid cycle begins • electron transport chain functions •carbon dioxide and water are formed •36 molecules of ATP produced per glucose molecule 4-17 .

Citric Acid Cycle .

Citric acid cycle .

Citric acid cycle inputs and outputs per glucose molecule • Inputs: • 2 acetyl groups • 6 NAD+ • 2 FAD • 2 ADP + 2 P • Outputs: • 4 CO2 • 6 NADH • 2 FADH2 • 2 ATP .

ATP forms as electrons are harvested.Aerobic Respiration • In aerobic respiration. – Oxygen is required! – Glucose is completely oxidized. • C6H12O6 + 6O2 6CO2 + 6H2O + energy Glucose Oxygen Carbon Dioxide Water (heat or ATP) . transferred along the electron transport chain and eventually donated to O2 gas.

– Occurs in cytoplasm – Doesn’t require O2 • Oxidation – harvests electrons and uses their energy to power ATP production. • Glycolysis – coupled reactions used to make ATP.3 Stages • Food is digested to break it into smaller pieces – no energy production here. – Only in mitochondria – More powerful .Cellular Respiration .

Mitochondria Inner Structure .

Organization of cristae .

• NADH molecules carry their electrons to the inner mitochondrial membrane where they transfer electrons to a series of membrane bound proteins – the electron transport chain.Using Electrons to Make ATP • NADH & FADH2 contain energized electrons. .

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– They must pass through special channels that will drive synthesis of ATP.Chemiosmosis • A strong gradient with many protons outside the matrix and few inside is set up.Producing ATP. • Oxidative phosphorylation . • Protons are driven back into the matrix.

• The citric acid cycle. . which occurs in the cytoplasm by substrate-level phosphorylation. there is a net gain of two ATP from glycolysis. also by substrate-level phosphorylation.Energy Yield from Glucose Metabolism • Per glucose molecule. occurring in the matrix of mitochondria. adds six more ATP.

ten NADH and two FADH2 take electrons to the electron transport system. • Electrons carried by NADH produced during glycolysis are shuttled to the electron transport chain by an organic molecule.Energy Yield from Glucose Metabolism • Most ATP is produced by the electron transport system and chemiosmosis. . three ATP are formed per NADH and two ATP per FADH2. • Per glucose molecule.

Accounting of energy yield per glucose molecule breakdown .

Glucose + 2 ATP + 36 ADP + 36 Pi + 6 O2 6CO2 + 2 ADP + 36 ATP + 6 H2O .

. – Oxidation of one 18-C stearic acid will net 146 ATP. • Fatty acids are oxidized and 2-C molecules break off as acetyl-CoA.Metabolism of Lipids • Triglycerides are broken down into glycerol and 3 fatty acid chains. so 1 triglyceride nets 462 ATP. – Oxidation of three glucose (18 Cs) nets 108 ATP. – Glycerol nets 22 ATP. • Glycerol enters glycolysis.

• Excess proteins can serve as fuel like carbohydrates and fats. . • Carbon skeletons oxidized. – Nitrogen is removed producing carbon skeletons and ammonia.Metabolism of Proteins • Proteins digested in the gut into amino acids which are then absorbed into blood and extracellular fluid.

but soluble. .Metabolism of Proteins • Ammonia is highly toxic. – Can be excreted by aquatic organisms as ammonia. • Terrestrial organisms must detoxify it first.

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Synthetic (Anabolic) pathways • Glycogen synthesis – Liver storage – Glucose to glycogen • Gluconeogenesis – Amino acids – Glycerol – Lactate Figure 4-29: Gluconeogenesis .

Lipogenesis Lipid synthesis .

Lipid Synthesis .

Introduction to Metabolism .

Biochemistry makes my head hurt!!” \ .“Alfonse.

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