CELLULAR RESPIRATION, CELLULAR RESPIRATION, FERMENTATION, AND SECONDARY FERMENTATION, AND SECONDARY

METABOLISMMETABOLISM

CHAPTER 7CHAPTER 7

Cellular respirationCellular respiration Process by which living cells obtain energy from organic Process by which living cells obtain energy from organic

moleculesmolecules Primary aim to make ATP and NADHPrimary aim to make ATP and NADH Aerobic respiration uses oxygenAerobic respiration uses oxygen– OO22 consumed and CO consumed and CO22 released released

Organic molecules + OOrganic molecules + O22 → CO → CO22 + H + H22O + EnergyO + Energy

Glucose metabolismGlucose metabolism 4 metabolic pathways4 metabolic pathways1.1. Glycolysis Glycolysis 2.2. Breakdown of pyruvate to an Breakdown of pyruvate to an

acetyl groupacetyl group3.3. Citric acid cycleCitric acid cycle4.4. Oxidative phosphorylationOxidative phosphorylation

Stage 1: GlycolysisStage 1: Glycolysis

Glycolysis can occur with or without Glycolysis can occur with or without oxygenoxygen

Steps in glycolysis nearly identical in all Steps in glycolysis nearly identical in all living speciesliving species

10 steps in 3 phases10 steps in 3 phases1.1. Energy investmentEnergy investment2.2. CleavageCleavage3.3. Energy liberationEnergy liberation

3 phases of glycolysis3 phases of glycolysis1.1. Energy investment Energy investment primingpriming

– Steps 1-3Steps 1-3– 2 ATP hydrolyzed to create fructose-1,6 bisphosphate2 ATP hydrolyzed to create fructose-1,6 bisphosphate

2.2. CleavageCleavage– Steps 4-5Steps 4-5– 6 carbon molecule broken into two 3 carbon molecules of 6 carbon molecule broken into two 3 carbon molecules of

glyceraldehyde-3-phosphateglyceraldehyde-3-phosphate3.3. Energy liberationEnergy liberation

– Steps 6-10Steps 6-10– Two glyceraldehyde-3-phosphate molecules broken down into two Two glyceraldehyde-3-phosphate molecules broken down into two

pyruvate molecules producing 2 NADH and 4 ATPpyruvate molecules producing 2 NADH and 4 ATP Net yield in ATP of 2Net yield in ATP of 2

Stage 2: Breakdown of pyruvate to an Stage 2: Breakdown of pyruvate to an acetyl group acetyl group

In eukaryotes, pyruvate in In eukaryotes, pyruvate in transported to the mitochondrial transported to the mitochondrial matrixmatrix

Broken down by pyruvate Broken down by pyruvate dehydrogenasedehydrogenase

Molecule of COMolecule of CO22 removed from removed from each pyruvateeach pyruvate

Remaining acetyl group attached Remaining acetyl group attached to CoA to make acetyl CoAto CoA to make acetyl CoA

1 NADH is made for each 1 NADH is made for each pyruvatepyruvate

Regulating aerobic Regulating aerobic respirationrespiration

Control of glucose catabolism occurs at Control of glucose catabolism occurs at three key points in the catabolic pathway. three key points in the catabolic pathway. -Glycolysis- phosphofructokinase, pyruvate -Glycolysis- phosphofructokinase, pyruvate oxidation-pyruvate decarboxylase and oxidation-pyruvate decarboxylase and krebs cycle- citrate syntehetasekrebs cycle- citrate syntehetase

Competitive inhibition: Krebs cycle, Competitive inhibition: Krebs cycle, oxaloacetate- inhibitor, enzyme- succinate oxaloacetate- inhibitor, enzyme- succinate dehydrogenase. Prevents making dehydrogenase. Prevents making fumerate. fumerate.

Stage 3: Citric acid cycle/ krebs Stage 3: Citric acid cycle/ krebs cycle/ tricarboxyclyic acid cyclecycle/ tricarboxyclyic acid cycle

Metabolic cycleMetabolic cycle– Particular molecules enter while other leave, involving a Particular molecules enter while other leave, involving a

series of organic molecules regenerated with each cycleseries of organic molecules regenerated with each cycle Acetyl is removed from Acetyl CoA and attached to Acetyl is removed from Acetyl CoA and attached to

oxaloacetate to form citrate or citric acidoxaloacetate to form citrate or citric acid Series of steps releases 2COSeries of steps releases 2CO22,and forms 1ATP, 3NADH, ,and forms 1ATP, 3NADH,

and 1 FADHand 1 FADH22 Oxaloacetate is regenerated to start the cycle againOxaloacetate is regenerated to start the cycle again

Stage 4: Oxidative phosphorylationStage 4: Oxidative phosphorylation High energy electrons removed from NADH and FADHHigh energy electrons removed from NADH and FADH22 to make ATP to make ATP Typically requires oxygenTypically requires oxygen Oxidative process involves electron transport chainOxidative process involves electron transport chain Phosphorylation occurs by ATP synthasePhosphorylation occurs by ATP synthase

Electron transport chainElectron transport chain Group of protein complexes and small Group of protein complexes and small

organic molecules embedded in the inner organic molecules embedded in the inner mitochondrial membranemitochondrial membrane

Can accept and donate electrons in a Can accept and donate electrons in a linear manner in a series of redox linear manner in a series of redox reactionsreactions

Movement of electrons generates HMovement of electrons generates H++ electrochemical gradient/ proton-motive electrochemical gradient/ proton-motive forceforce– Excess of positive charge outside of Excess of positive charge outside of

matrixmatrix

Free energy changeFree energy change

Movement from NADH to Movement from NADH to OO22 is a very negative free is a very negative free energy changeenergy change– Spontaneous in Spontaneous in

forward directionforward direction Highly exergonicHighly exergonic Some energy used to Some energy used to

pump Hpump H+ + across inner across inner mitochondrial membrane mitochondrial membrane and create Hand create H++ electrochemical gradientelectrochemical gradient

Theortetical atp yield of Theortetical atp yield of aerobic respirtationaerobic respirtation

Glucose is entirel consumed on of the carbons in pyruvate is lost Glucose is entirel consumed on of the carbons in pyruvate is lost as co2 in the conversion to acetyl coa two other carbons are lost as co2 in the conversion to acetyl coa two other carbons are lost during the oxidations of the krebs cuclee and two molecules of during the oxidations of the krebs cuclee and two molecules of atp make glycolysisatp make glycolysis

Tywo more atp molecules have been made in krebsTywo more atp molecules have been made in krebs Tweleve electron carriers have been reduced 10 nadph and two Tweleve electron carriers have been reduced 10 nadph and two

fadh2 and h has built up so actually yield is 30 molecules of atpfadh2 and h has built up so actually yield is 30 molecules of atp 1. leaking inner mitchondrial membrane1. leaking inner mitchondrial membrane 2. h+gradient uptake of pyruvate 3. nadh energy to other 2. h+gradient uptake of pyruvate 3. nadh energy to other

molecules molecules 4. atps from substrate phosphory lation 25. nadh 2.5/ 10 4. atps from substrate phosphory lation 25. nadh 2.5/ 10

molecule 3. fadhs 1.5/2 molecules equals 32 and minus 2 for molecule 3. fadhs 1.5/2 molecules equals 32 and minus 2 for transport of glycolytic nadh equals 30transport of glycolytic nadh equals 30

7.3x30/686= 32% efficiency7.3x30/686= 32% efficiency

ATP synthaseATP synthase Enzyme harnesses free energy as HEnzyme harnesses free energy as H++ flow flow

through membrane embedded regionthrough membrane embedded region Energy conversion- HEnergy conversion- H++ electrochemical electrochemical

gradient or proton motive force converted gradient or proton motive force converted to chemical bond energy in ATPto chemical bond energy in ATP

Racker and Stoeckenius confirmed ATP Racker and Stoeckenius confirmed ATP uses an Huses an H++ electrochemical gradient electrochemical gradient

Rotary machine that makes ATP as it Rotary machine that makes ATP as it spinsspins

Yoshida and Kinosita demonstrated that the Yoshida and Kinosita demonstrated that the γγ subunit subunit of the ATP synthase spinsof the ATP synthase spins

Masasuke Yoshida, Kazuhiko Masasuke Yoshida, Kazuhiko Kinosita, and colleagues set out to Kinosita, and colleagues set out to experimentally visualize the experimentally visualize the rotary nature of the ATP synthaserotary nature of the ATP synthase

Released membrane embedded Released membrane embedded portion and adhered it to a slideportion and adhered it to a slide

Visualize g subunit using Visualize g subunit using fluorescencefluorescence

Added ATP to make reaction run Added ATP to make reaction run backwardbackward

Rotated counterclockwise to Rotated counterclockwise to hydrolyze ATPhydrolyze ATP– Rotate clockwise to synthesize Rotate clockwise to synthesize

ATPATP

Cancer cells usually favor glycolysisCancer cells usually favor glycolysis Many disease associated with alterations Many disease associated with alterations

in carbohydrate metabolismin carbohydrate metabolism Warburg effect- cancer cells Warburg effect- cancer cells

preferentially use glycolysis while preferentially use glycolysis while decreasing oxidative phosphorylation decreasing oxidative phosphorylation {18F] fluorodeoxyglucose{18F] fluorodeoxyglucose

Used to diagnose cancers in PET scansUsed to diagnose cancers in PET scans Glycolytic enzymes overexpressed in 80% Glycolytic enzymes overexpressed in 80%

of all types of cancersof all types of cancers Caused by genetic and environmental Caused by genetic and environmental

factors- mutations and low oxygenfactors- mutations and low oxygen– Von hippel-lindau syndromeVon hippel-lindau syndrome– -hypoxia-hypoxia

Other organic moleculesOther organic molecules Other carbohydrates, proteins Other carbohydrates, proteins

and fats also used for energyand fats also used for energy Enter into glycolysis or citric Enter into glycolysis or citric

acid cycle at different pointsacid cycle at different points Utilizing the same pathways Utilizing the same pathways

for breakdown increases for breakdown increases efficiencyefficiency

Metabolism can also be used to Metabolism can also be used to make other molecules make other molecules (anabolism)(anabolism)

Other acceptorsOther acceptors E. coli uses nitrate (NOE. coli uses nitrate (NO33

--) ) under anaerobic conditionsunder anaerobic conditions

Makes ATP via chemiosmosis Makes ATP via chemiosmosis even under aerobic conditionseven under aerobic conditions

Anaerobic metabolismAnaerobic metabolism For environments that lack For environments that lack

oxygen or during oxygen oxygen or during oxygen deficitsdeficits

2 strategies2 strategies– Use substance other Use substance other

than Othan O22 as final electron as final electron acceptor in electron acceptor in electron transport chaintransport chain

– Produce ATP only via Produce ATP only via substrate-level substrate-level phosphorylationphosphorylation

FermentationFermentation Some organisms cannot use OSome organisms cannot use O22 as final electron acceptor as final electron acceptor Make ATP via glycolysis onlyMake ATP via glycolysis only Need to regenerate NADNeed to regenerate NAD++ to keep glycolysis running to keep glycolysis running Muscle cells produce lactateMuscle cells produce lactate Yeast make ethanolYeast make ethanol Produces far less ATPProduces far less ATP

Secondary MetabolismSecondary Metabolism Primary metabolism- essential for cell structure Primary metabolism- essential for cell structure

and functionand function Secondary metabolism- synthesis of secondary Secondary metabolism- synthesis of secondary

metabolites that are not necessary for cell metabolites that are not necessary for cell structure and growthstructure and growth

Secondary metabolites unique to a species or Secondary metabolites unique to a species or groupgroup

Roles in defense, attraction, protection, Roles in defense, attraction, protection, competitioncompetition

4 categories4 categories

Phenolics- flavonoids, tannins ,ligninsPhenolics- flavonoids, tannins ,lignins– Antioxidants with intense flavors Antioxidants with intense flavors

and smellsand smells Alkaloids- caffeine nicotine atropineAlkaloids- caffeine nicotine atropine– Bitter-tasting molecules for defenseBitter-tasting molecules for defense

Terpenoids cinnamon fennel clovesTerpenoids cinnamon fennel cloves– Intense smells and colorsIntense smells and colors

Polyketides derivatives of acetyl and Polyketides derivatives of acetyl and propionyl gorupspropionyl gorups– Chemical weapons,Chemical weapons,– Cure cancerCure cancer