Chapter 19 Bioenergetics - PowerPoint PPT Presentation

How the Body Converts Food to Energy

• Metabolism: the sum of all chemical reactions involved in maintaining the dynamic state of a cell or organism
• pathway: a series of consecutive biochemical reactions
• catabolism: the biochemical pathways that are involved in generating energy by breaking down large nutrient molecules into smaller molecules with the concurrent production of energy
• anabolism: the pathways by which biomolecules are synthesized (use ATP energy to build larger molecules from smaller building blocks)

• metabolism is the sum of catabolism and anabolism

Catabolic reactions are organized into three stages:

• In Stage 1, digestion breaks down large molecules into smaller ones that enter the bloodstream
• In Stage 2, molecules enter the cells and are broken down into two- and three-carbon compounds
• In Stage 3, compounds are oxidized in the citric acid cycle to provide energy (ATP) for anabolic processes

• Animal cells have many components, each with specific functions; some components along with one or more of their functions are:
• nucleus: where replication of DNA takes place
• lysosomes: remove damaged cellular components and some unwanted foreign materials
• Golgi bodies: package and process proteins for secretion and delivery to other cellular components
• mitochondria: responsible for generation of most of the energy for cells

• Schematic of a mitochondrion cut to reveal its inner organization

• The two parts to the common catabolic pathway
• citric acid cycle, also called the tricarboxylic acid or Krebs cycle
• oxidative phosphorylation, also called the electron transport chain, or the respiratory chain
• The four principal compounds participating in the common catabolic pathway are:
• AMP, ADP, and ATP
• NAD+/NADH
• FAD/FADH2
• coenzyme A; abbreviated CoA or CoA-SH

• ATP is the most important compound involved in the transfer of phosphate groups
• ATP contains two phosphoric anhydride bonds and one phosphoric ester bond

• hydrolysis of the terminal phosphate of ATP gives ADP, phosphate ion, and energy
• hydrolysis of a phosphoric anhydride liberates more energy than hydrolysis of a phosphoric ester
• we say that ATP and ADP contain high-energy phosphoric anhydride bonds
• ATP is a universal carrier of phosphate groups
• it is also a common currency for the storage and transfer of energy

• The hydrolysis of ATP to ADP releases 7.3 kcal (31 kJ/mole)

ATP  ADP + Pi + 7.3 kcal (31 kJ/mole)

• The hydrolysis of ADP to AMP releases 7.3 kcal (31 kJ/mole)

ADP  AMP + Pi + 7.3 kcal (31 kJ/mole)

• Nicotinamide adenine dinucleotide (NAD+) is a biological oxidizing agent

• NAD+ is a two-electron oxidizing agent, and is reduced to NADH
• NADH is a two-electron reducing agent, and is oxidized to NAD+
• NAD+ and NADH are also hydrogen ion transporting molecules

• When a compound is oxidized by an enzyme, 2H+ and 2e- are removed by a coenzyme, which is reduced
• NAD+ (nicotinamide adenine dinucleotide) participates in reactions that produce a carbon-oxygen double bond (C=O)
• For example, NAD+ participates in the oxidation of ethanol:

• Flavin adenine dinucleotide (FAD) is also a biological oxidizing agent

• FAD is a two-electron oxidizing agent, and is reduced to FADH2
• FADH2 is a two-electron reducing agent, and is oxidized to FAD

• FAD participates in reactions that produce a carbon-carbon double bond (C=C)

Oxidation

—CH2—CH2—  —CH=CH— + 2H+ + 2e-

Reduction

FAD + 2H+ + 2e- FADH2

• Coenzyme A (CoA) is an acetyl-carrying group
• like NAD+ and FAD, coenzyme A contains a unit of ADP
• CoA is often written CoA-SH to emphasize the fact that it contains a sulfhydryl group
• the vitamin part of coenzyme A is pantothenic acid
• the acetyl group of acetyl CoA is bound as a high-energy thioester

• overview: the two carbon acetyl group of acetyl CoA is fed into the cycle and oxidized to 2 CO2
• there are four oxidation steps in the cycle

• Step 1: condensation of acetyl CoA with oxaloacetate
• the high-energy thioester of acetyl CoA is hydrolyzed
• this hydrolysis provides the energy to drive Step 1
• citrate synthase is an allosteric enzyme; it is inhibited by NADH, ATP, and succinyl-CoA

• Step 2: dehydration and rehydration, catalyzed by aconitase, gives isocitrate
• citrate is achiral; it has no stereocenter
• aconitate is also achiral
• isocitrate is chiral; it has 2 stereocenters and 4 stereoisomers are possible
• only one of the 4 possible stereoisomers is formed in the cycle

• Step 2 (cont’d): Citrate isomerizes to isocitrate
• The tertiary –OH group in citrate is converted to a secondary –OH that can be oxidized

• Step 3: oxidation of isocitrate followed by decarboxylation gives a-ketoglutarate
• isocitrate dehydrogenase is an allosteric enzyme; it is inhibited by ATP and NADH, and activated by ADP and NAD+

• Step 4: oxidative decarboxylation of -ketoglutarate to succinyl-CoA
• the two carbons of the acetyl group of acetyl CoA are still present in succinyl CoA and in succinate
• this multienzyme complex is inhibited by ATP, NADH, and succinyl CoA; it is activated by ADP and NAD+

• Step 5: formation of succinate
• the two CH2-COO- groups of succinate are now equivalent
• this is the first energy-yielding step of the cycle; a molecule of GTP is produced

• Step 6: oxidation of succinate to fumarate
• Step 7: hydration of fumarate to L-malate
• L-malate is chiral and can exist as a pair of enantiomers; it is produced in the citric acid cycle as a single stereoisomer

• Step 8: oxidation of malate
• oxaloacetate now can react with acetyl CoA to start another round of the cycle by repeating Step 1

In one turn of the citric acid cycle:

• Two decarboxylations remove two carbons as 2CO2
• Four oxidations provide hydrogen for 3NADH and one FADH2
• A direct phosphorylation forms GTP which is used to form ATP

Overall reaction of citric acid cycle:

• Control of the cycle
• controlled by three feedback mechanisms
• citrate synthase: inhibited by ATP, NADH, and succinyl CoA; also product inhibition by citrate
• isocitrate dehydrogenase: activated by ADP and NAD+, inhibited by ATP and NADH
• -ketoglutarate dehydrogenase complex: inhibited by ATP, NADH, and succinyl CoA; activated by ADP and NAD+

• The catabolism of proteins, carbohydrates, and fatty acids all feed into the citric acid cycle at one or more points

• The electron transport chain consists of electron carriers that accept H+ ions and electrons from the reduced coenzymes NADH and FADH2
• The H+ ions and electrons are passed down a chain of carriers until in the last step they combine with oxygen to form H2O
• Oxidative phosphorylation is the process by which the energy from transport is used to synthesize ATP

• Carried out by four closely related multisubunit membrane-bound complexes and two electron carriers, coenzyme Q and cytochrome c
• in a series of oxidation-reduction reactions, electrons from FADH2 and NADH are transferred from one complex to the next until they reach O2
• O2 is reduced to H2O
• as a result of electron transport, protons are pumped across the inner membrane to the intermembrane space

• The electron carriers in the electron transport system are attached to the inner membrane of the mitochondrion
• They are organized into four protein complexes:

Complex I NADH dehydrogenase

Complex II Succinate dehydrogenase

Complex III CoQ-Cytochrome c reductase

Complex IV Cytochrome c Oxidase

• The sequence starts with complex I
• this large complex contains some 40 subunits, among them are a flavoprotein, several iron-sulfur (FeS) clusters, and coenzyme Q (CoQ, ubiquinone)
• complex I oxidizes NADH to NAD+
• the oxidizing agent is CoQ, which is reduced to CoQH2
• some of the energy released in this reaction is used to move 2H+ from the matrix into the intermembrane space

• complex II oxidizes FADH2 to FAD
• the oxidizing agent is CoQ, which is reduced to CoQH2
• the energy released in this reaction is not sufficient to pump protons across the membrane

• complex III delivers electrons from CoQH2 to cytochrome c (Cyt c)
• this integral membrane complex contains 11 subunits, including cytochrome b, cytochrome c1, and FeS clusters
• complex III has two channels through which the two H+ from CoQH2 are pumped from the matrix into the intermembrane space

• complex IV is also known as cytochrome oxidase
• it contains 13 subunits, one of which is cytochrome a3
• electrons flow from Cyt c (oxidized) in complex III to Cyt a3 in complex IV
• from Cyt a3 electrons are transferred to O2
• during this redox reaction, H+ are pumped from the matrix into the intermembrane space
• Summing the reactions of complexes I - IV, six H+ are pumped out per NADH and four H+ per FADH2

• To explain how electron and H+ transport produce the chemical energy of ATP, Peter Mitchell proposed the chemiosmotic theory
• the energy-releasing oxidations give rise to proton pumping and a pH gradient across the inner mitochondrial membrane
• there is a higher concentration of H+ in the intermembrane space than inside the mitochondrion
• this proton gradient provides the driving force to propel protons back into the mitochondrion through the enzyme complex called proton translocating ATPase

• protons flow back into the matrix through channels in the F0 unit of ATP synthase
• the flow of protons is accompanied by formation of ATP in the F1 unit of ATP synthase
• The functions of oxygen are:
• to oxidize NADH to NAD+ and FADH2 to FAD so that these molecules can return to participate in the citric acid cycle
• provide energy for the conversion of ADP to ATP

• The overall reactions of oxidative phosphorylation are:

• A portion of the energy released during electron transport is now built into ATP
• for each two-carbon acetyl unit entering the citric acid cycle, we get three NADH and one FADH2
• for each NADH oxidized to NAD+, we get three ATP
• for each FADH2 oxidized to FAD, we get two ATP
• thus, the yield of ATP per two-carbon acetyl group oxidized to CO2 is

• The chemical energy of ATP is converted by the body to several other forms of energy
• Electrical energy
• the body maintains a K+ concentration gradient across cell membranes; higher inside and lower outside
• it also maintains a Na+ concentration gradient across cell membranes; lower inside, higher outside
• Special transport proteins in cell membranes constantly pump K+ into and Na+ out of the cells
• this pumping requires energy, which is supplied by the hydrolysis of ATP to ADP
• thus, the chemical energy of ATP is transformed into electrical energy, which operates in neurotransmission

• Mechanical energy
• ATP drives the alternating association and dissociation of actin and myosin and, consequently, the contraction and relaxation of muscle tissue
• Heat energy
• hydrolysis of ATP to ADP yields 7.3 kcal/mol
• some of this energy is released as heat to maintain body temperature

End

Chapter 19