clicker question monosaccharide sugars and amino acids first enter the blood stream at the: a....
TRANSCRIPT
Clicker QuestionClicker Question
Monosaccharide sugars and amino Monosaccharide sugars and amino acids first enter the blood stream at acids first enter the blood stream at the:the:
A.A. capillaries in the small intestinecapillaries in the small intestine
B.B. capillaries in the stomachcapillaries in the stomach
C.C. left atriumleft atrium
D.D. right atriumright atrium
E.E. capillaries in the salivary glandscapillaries in the salivary glands
Where are we?Where are we?• Last time I discussed:Last time I discussed:
– The circulatory system and the The circulatory system and the transport of oxygen, glucose and transport of oxygen, glucose and other nutrients throughout the body.other nutrients throughout the body.
– Heart attacks, strokes and Heart attacks, strokes and pulmonary embolisms.pulmonary embolisms.
– The heart and lungs.The heart and lungs.
• Speaking of hearts and lungs, Speaking of hearts and lungs, – We sang together (with Chloe): We sang together (with Chloe): “How “How
do you measure, a year in the life?”do you measure, a year in the life?”
• Today we will cover:Today we will cover:– Cellular respiration and the Cellular respiration and the
biosynthesis of molecules.biosynthesis of molecules.
With a Little Help from My With a Little Help from My FriendsFriends
• Take a couple minutes to meet Take a couple minutes to meet or get to know a little better or get to know a little better the people sitting around you. the people sitting around you.
• Make sure that nobody is left Make sure that nobody is left out.out.
• Study through livingStudy through living. Study . Study nutrition, digestion, etc. nutrition, digestion, etc. together over lunch or dinner! together over lunch or dinner!
Joe Cocker With a Little Help from My Friends Woodstock 1969
Bethel Woods Center for the Arts
Town of Bethel, New York
With a Little Help from My Friends with Clapton, Page and Beck
Cells Differ Because the Specifics of a Cells Differ Because the Specifics of a Cell Depend on Its Functional Cell Depend on Its Functional
SpecializationSpecialization • Each Each cellcell has the basic has the basic
organelles organelles of a eukaryotic cell. of a eukaryotic cell. However, the However, the proportion proportion and and positionposition of each organelle of each organelle depends on the cell type.depends on the cell type.
• Each cell has the Each cell has the basic basic chemicalschemicals required for life, required for life, however, the however, the precursors precursors required by each cell, the required by each cell, the rate rate of turnover of turnover of the chemicals, of the chemicals, and the and the chemicals producedchemicals produced by each cell differ depending on by each cell differ depending on cell type.cell type.
• The The structurestructure and chemical and chemical composition of a cell depends on composition of a cell depends on the the functionfunction of the cell in an of the cell in an organ.organ.
However Almost All Cells However Almost All Cells Require Glucose and Oxygen to Require Glucose and Oxygen to
Make ATPMake ATP• Every cell “burns” Every cell “burns” glucoseglucose as an as an
energy source to synthesize energy source to synthesize ATPATP from from ADP and Pi. ADP and Pi.
• Each cell also uses the carbon skeleton Each cell also uses the carbon skeleton of glucose to synthesize chemicals of glucose to synthesize chemicals that are necessary for that cell.that are necessary for that cell.
• The majority of cells burn glucose The majority of cells burn glucose completely during cellular respiration.completely during cellular respiration.– The complete combustion of glucose The complete combustion of glucose
requiresrequires oxygen. oxygen. Aerobic respiration Aerobic respiration results in about results in about 38 ATP/glucose38 ATP/glucose..
– Some fast twitch muscle cells burn glucose Some fast twitch muscle cells burn glucose quickly but incompletely in the absence of quickly but incompletely in the absence of oxygen. This oxygen. This anaerobic respirationanaerobic respiration results in only results in only 2 ATP/glucose2 ATP/glucose..
Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings
Figure 5.2B Aerobic Energy transformations in a cell
Heat
Chemical reactions
ATP ATP
Glucose
+
Oxygen
water
Carbon dioxide
+
Energy for cellular work
Burning: The combination of oxygen with a reduced carbon source which yields carbon dioxide, water and heat.
From
the
aorta
Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings
Figure 6.2 We must breathe so that the cells of our body get oxygen and eliminate carbon dioxide
CO2
CO2
O2
O2Bloodstream
Muscle cells carrying out
Cellular Respiration
Breathing
Glucose O2
CO2 H2O ATP
Lungs
First Law of First Law of ThermodynamicsThermodynamics
• Energy cannot be Energy cannot be created or created or destroyed.destroyed.
• That is, our bodies That is, our bodies require require energyenergy for the organs to for the organs to do their do their workwork and and we get that we get that energy by eating energy by eating food.food.
We Need to Eat Approximately We Need to Eat Approximately 1600 Calories/Day Just to Maintain 1600 Calories/Day Just to Maintain
the Bodythe Body
Various Various activities use activities use up additional up additional Calories Calories (=kcal).(=kcal).
McDonalds
Wendy's
Burger King
Putting the Number and Putting the Number and Distribution of Calories in Distribution of Calories in
PerspectivePerspective
clintonbushhaitifund.org www.redcross.org www.unicef.org/
• If you eat a Quarter If you eat a Quarter
Pounder with Cheese, a Pounder with Cheese, a medium French Fries and medium French Fries and drink a medium Classic drink a medium Classic Coke, you take in Coke, you take in 1110 1110 CaloriesCalories..
• These are enough Calories These are enough Calories to allow you to run 7 minute to allow you to run 7 minute miles for about 1.4 hours.miles for about 1.4 hours.
• If you don’t run for 1.4 If you don’t run for 1.4 hours (or do an equivalent hours (or do an equivalent amount of work), you will amount of work), you will store the Calories as 123 g store the Calories as 123 g of fat (about ¼ of a pound) of fat (about ¼ of a pound) since fat has a fuel value of since fat has a fuel value of 9 Calories/gram. 9 Calories/gram.
There Are Other Ways to Burn There Are Other Ways to Burn CaloriesCalories
Fat is GoodFat is Good
• FatFat is a very efficient is a very efficient form of form of energy energy storagestorage since 1 gram since 1 gram of fat can store 9 of fat can store 9 Calories, whereas 1 Calories, whereas 1 gram of carbohydrate or gram of carbohydrate or 1 gram of protein can 1 gram of protein can only store 4 Calories. only store 4 Calories.
• If we stored energy as If we stored energy as carbohydrate or as carbohydrate or as protein, we would weigh protein, we would weigh more than we do.more than we do.
Fat is a Light Way to Store CaloriesFat is a Light Way to Store Calories
• ~ 2000 Calories can be stored by ~½ pound of fat in our ~ 2000 Calories can be stored by ~½ pound of fat in our body.body.
– (2000 Calories) (1 g fat/9 Calories)(2.2 pounds/1000 g) = 0.49 (2000 Calories) (1 g fat/9 Calories)(2.2 pounds/1000 g) = 0.49 pounds of fatpounds of fat
• ~ 2000 Calories would be stored as ~ 1 pound of protein ~ 2000 Calories would be stored as ~ 1 pound of protein or ~ 1 pound of carbohydrate in our body.or ~ 1 pound of carbohydrate in our body.
– (2000 Calories) (1 g protein or carbohydrate/4 Calories)(2.2 (2000 Calories) (1 g protein or carbohydrate/4 Calories)(2.2 pounds/1000 g) = 1.1 pounds of protein or carbohydratepounds/1000 g) = 1.1 pounds of protein or carbohydrate
Although Storing too Many Calories as Although Storing too Many Calories as Fat (BMI Fat (BMI >>30) is Unhealthy 30) is Unhealthy
Skeletal Muscle Cells Burn (Oxidize) Skeletal Muscle Cells Burn (Oxidize) Calories When We Do WorkCalories When We Do Work
• The food (glucose) is The food (glucose) is oxidized oxidized (loss of (loss of electrons and their accompanying protons) by electrons and their accompanying protons) by oxygenoxygen to form carbon dioxide, water and to form carbon dioxide, water and available energy (available energy (ATPATP).).
• The oxygen is reduced (gain of electrons and The oxygen is reduced (gain of electrons and their accompanying protons) to form water.their accompanying protons) to form water.
• The ATP formed is used for muscle contraction.The ATP formed is used for muscle contraction.
Food is Oxidized by a Class of Food is Oxidized by a Class of Enzymes Called Enzymes Called DehydrogenasesDehydrogenases
The dehydrogenases work by transferring the The dehydrogenases work by transferring the electrons and their accompanying protons to electrons and their accompanying protons to NADNAD to make to make NADH.NADH.
ATP is then Formed By a Controlled ATP is then Formed By a Controlled Oxidation of NADH by an Electron Transport Oxidation of NADH by an Electron Transport
ChainChain
• The burning of wood The burning of wood is an is an uncontrolled uncontrolled release of energy in release of energy in the form of heat.the form of heat.
• By passing By passing electrons stepwise electrons stepwise though the electron though the electron transport chain, the transport chain, the energy of NADH energy of NADH can be conserved can be conserved in ATP moleculesin ATP molecules with a minimal loss with a minimal loss as heat.as heat.
The Controlled Burning of Food For The Controlled Burning of Food For Energy Occurs in the Cytoplasm Energy Occurs in the Cytoplasm
((GlycolysisGlycolysis) and the Mitochondrion ) and the Mitochondrion ((Krebs CycleKrebs Cycle and and ElectronElectron
Transport Chain)Transport Chain)
As the Electrons Travel from NADH to As the Electrons Travel from NADH to Oxygen through Various Acceptors of Oxygen through Various Acceptors of
the Electron Transport Chain, They Pull the Electron Transport Chain, They Pull Protons Across a Membrane and Form Protons Across a Membrane and Form
an Electrical Battery that can Make ATPan Electrical Battery that can Make ATP
Respiratory Poisons, Including Cyanide Respiratory Poisons, Including Cyanide and Carbon Monoxide, Inhibit Electron and Carbon Monoxide, Inhibit Electron Transport and Prevent ATP FormationTransport and Prevent ATP Formation
The Carbohydrates, Fats and The Carbohydrates, Fats and Proteins Enter the Respiratory Proteins Enter the Respiratory
Pathway in Various Places to Make Pathway in Various Places to Make ATPATP
This is a This is a miraclemiracle. . ImagineImagine a car a car engine engine that that could could run on run on gas, gas, butter, butter, peanuts peanuts and hay.and hay.
Perhaps One Day a Car will be able Perhaps One Day a Car will be able to Run on All Wastesto Run on All Wastes
Many Molecules in Cells are Many Molecules in Cells are Synthesized from Intermediates Synthesized from Intermediates
Formed During RespirationFormed During Respiration
• Some of the food Some of the food molecules are molecules are incompletely oxidized incompletely oxidized and are and are transformedtransformed into into other molecules. other molecules.
• The The ATPATP is used to do is used to do muscular workmuscular work andand to put together to put together carbon skeletons in carbon skeletons in the the biosynthesisbiosynthesis of of macromoleculesmacromolecules..
The Discovery of Cellular The Discovery of Cellular RespirationRespiration
• That is cellular That is cellular respiration and respiration and biosynthesis in a biosynthesis in a nutshell. nutshell.
• How were these How were these miraculous miraculous processes processes discovered?discovered?
• It all started with It all started with Robert Boyle Robert Boyle (1662) and his (1662) and his vacuum pump.vacuum pump.
Robert Boyle Accidentally Discovered that Robert Boyle Accidentally Discovered that Air Is Necessary for LifeAir Is Necessary for Life
• Robert Boyle was Robert Boyle was conducting experiments to conducting experiments to see whether butterflies see whether butterflies could fly in could fly in air made thinair made thin by his newly invented by his newly invented vacuum pump. vacuum pump.
• When he pulled a When he pulled a vacuum vacuum in the bell jar, in which they in the bell jar, in which they were flying, the butterflies were flying, the butterflies fell down and died.fell down and died.
• Did they die as a Did they die as a consequence of the fall or consequence of the fall or did they become weak did they become weak because they needed air? because they needed air?
Robert Boyle Accidentally Robert Boyle Accidentally Discovered that Air Is Necessary Discovered that Air Is Necessary
for Lifefor Life
• Boyle realized that the air Boyle realized that the air was necessary for life was necessary for life after he repeated his after he repeated his experiments using a experiments using a lark lark with a broken wingwith a broken wing. . Since the lark could not Since the lark could not fly, any adverse effects of fly, any adverse effects of the lack of air on the lark the lack of air on the lark in the bell jar would not in the bell jar would not be caused by falling but be caused by falling but would indicate the would indicate the necessity of air for life. necessity of air for life.
• The lark died in the The lark died in the vacuum, showing that vacuum, showing that air air is necessary for lifeis necessary for life..
Mice also Need Air to LiveMice also Need Air to Live
• By putting a mouse in By putting a mouse in a bell jar and a bell jar and removing the air with removing the air with a vacuum, Boyle a vacuum, Boyle showed that air was showed that air was also a necessity for also a necessity for mice.mice.
• But his But his criticscritics suggested that the suggested that the animals might have animals might have died from being in an died from being in an uncomfortable place, uncomfortable place, claustrophobia or the claustrophobia or the lack of food.lack of food.
Robert Boyle Performed Controls to Robert Boyle Performed Controls to Convince CriticsConvince Critics
In response to his critics, Boyle put a mouse in the In response to his critics, Boyle put a mouse in the bell jar overnight, gave it a paper bed and plenty bell jar overnight, gave it a paper bed and plenty of cheese and then placed the bell jar by the of cheese and then placed the bell jar by the fireside to keep the mouse warm during the night.fireside to keep the mouse warm during the night.
Robert Boyle Performs Controls Robert Boyle Performs Controls to Convince Criticsto Convince Critics
• In the morning, Boyle In the morning, Boyle observed that the observed that the mouse was very much mouse was very much alive. alive.
• However, as soon as However, as soon as Boyle evacuated the air, Boyle evacuated the air, the mouse started to the mouse started to die, showing that lack of die, showing that lack of air, and not the lack of air, and not the lack of ““creature comfortscreature comforts” ” was necessary for life.was necessary for life.
Air is Taken Up By The Air is Taken Up By The LungsLungs
Robert Hooke (1726), an Robert Hooke (1726), an assistant of Boyle’s and all assistant of Boyle’s and all around genius, showed that around genius, showed that the air was taken up by the the air was taken up by the lungs by demonstrating that lungs by demonstrating that a dog whose a dog whose diaphragmdiaphragm was not working could be was not working could be kept alive if air was kept alive if air was continuously blown with a continuously blown with a bellows bellows through the through the lungslungs, , but not through other parts but not through other parts of the body. of the body.
Oxygen is the Vital Part of the Oxygen is the Vital Part of the AirAir
• Joseph Priestley (1774) furthered the work of Joseph Priestley (1774) furthered the work of Boyle and Hooke when he showed that Boyle and Hooke when he showed that animals took up the part of the air that was animals took up the part of the air that was necessary for a candle to burn.necessary for a candle to burn.
• Thus Thus oxygen was the vital part of the airoxygen was the vital part of the air that was taken up by the respiration of that was taken up by the respiration of animals.animals.
Carl Djerassi and Roald Carl Djerassi and Roald HoffmannHoffmann
Antoine Lavoisier Showed that the Antoine Lavoisier Showed that the Combustion of Food during Respiration is Combustion of Food during Respiration is
Chemically Like the Burning of WoodChemically Like the Burning of Wood
• Also in the 1770s, Antoine Also in the 1770s, Antoine Lavoisier, the founder of Lavoisier, the founder of modern chemistry, modern chemistry, determined that determined that combustioncombustion results from results from the combination of the combination of oxygen oxygen with with carbon carbon andand hydrogenhydrogen..
• Lavoisier believed that Lavoisier believed that respiration and respiration and combustion were combustion were analogousanalogous reactions. reactions.
• Lavoisier used Lavoisier used analogyanalogy to to discover new phenomena.discover new phenomena.
““In respiration, as in In respiration, as in combustion, it is the combustion, it is the atmospheric air which atmospheric air which furnished oxygen…; but furnished oxygen…; but since in respiration it is…since in respiration it is…the blood, which furnishes the blood, which furnishes the combustion matter, if the combustion matter, if animals did not regularly animals did not regularly replace by means of food…replace by means of food…that which they lose by that which they lose by respiration, the lamp would respiration, the lamp would soon lack oil, and the soon lack oil, and the animal would perish as a animal would perish as a lamp is extinguished when lamp is extinguished when it lacks nourishment.” it lacks nourishment.”
““The proofs of this identity of effects in respiration The proofs of this identity of effects in respiration and combustion are immediately deducible from and combustion are immediately deducible from experiment. Indeed, upon leaving the lung, the air experiment. Indeed, upon leaving the lung, the air that has been used for respiration no longer that has been used for respiration no longer contains the same amount of oxygen; it contains contains the same amount of oxygen; it contains not only carbonic acid gas but also much more not only carbonic acid gas but also much more water than it contained before it had been water than it contained before it had been inspired.”inspired.”
Formula for Combustion and Formula for Combustion and RespirationRespiration
C(HC(H22O) + OO) + O22 CO CO22 + H + H22O + heat O + heat
• Respiration Respiration was defined as a was defined as a combustioncombustion process and measured by the uptake of Oprocess and measured by the uptake of O22
and the expulsion of COand the expulsion of CO22 and H and H22O.O.• Using a melting ice Using a melting ice calorimetercalorimeter, Lavoisier , Lavoisier
and Pierre Simon de Laplace found that for and Pierre Simon de Laplace found that for equal outputs of COequal outputs of CO22, approximately the , approximately the same amount of ice was melted by the same amount of ice was melted by the respiration of a guinea pig and the burning respiration of a guinea pig and the burning of charcoal. of charcoal.
• Lavoisier believed that the Lavoisier believed that the heat heat provided provided the energy necessary for the processes we the energy necessary for the processes we associate with life.associate with life.
Political Correctness and Political Correctness and ScienceScience
• Like Priestley, Like Priestley, Lavoisier never Lavoisier never finished his finished his experiments on experiments on respiration because respiration because he was “politically he was “politically incorrect”.incorrect”.
• Lavoisier, who was Lavoisier, who was a tax collector, lost a tax collector, lost his head in a his head in a guillotine during the guillotine during the French Revolution.French Revolution.
Lectures on Respiration for Lectures on Respiration for ChildrenChildren
faraday
(Almost) All Cells Respire
• Scientists disagreed as to where the conversion of O2 to CO2 took place.
Was it the lungs or was it the blood?
• This was a false dichotomy. The conversion occurred in both places, as well as in (almost) every other part of the organism, as Lazzaro Spallanzani (1803) showed when he isolated various tissues and demonstrated that all tissues were capable of consuming O2 and
giving off CO2.
Measure oxygen uptake (↑) or carbon dioxide evolution (↓).
The Crucial Secret…Respiration is a Cellular The Crucial Secret…Respiration is a Cellular Process Common to All CellsProcess Common to All Cells
Many biologists still did not believe Many biologists still did not believe that respiration occurred outside that respiration occurred outside the blood. Eduard Pflüger (1872) the blood. Eduard Pflüger (1872) removed the blood of a frog and removed the blood of a frog and replaced it with saline and found replaced it with saline and found that this frog respired just like a that this frog respired just like a normal frog. He also mentioned that normal frog. He also mentioned that insects and plants that have no insects and plants that have no blood respire tooblood respire too. Pflüger . Pflüger concluded, concluded, "Here lies, and I want to "Here lies, and I want to state this once and for all, the state this once and for all, the crucial secret of the regulation of crucial secret of the regulation of the total oxygen consumption by the total oxygen consumption by the organism, a gravity which is the organism, a gravity which is entirely determined by the entirely determined by the cell cell itselfitself....“....“
The Scientific Method: A Critical The Scientific Method: A Critical Attitude is Clearly Required…Attitude is Clearly Required…
According to Thomas Gold (1989), According to Thomas Gold (1989), “New ideas in science are not “New ideas in science are not always right just because they always right just because they are new. Nor are the old ideas are new. Nor are the old ideas always wrong just because always wrong just because they are old. A critical they are old. A critical attitude is clearly required of attitude is clearly required of every scientist….. Whenever every scientist….. Whenever the established ideas are the established ideas are accepted uncritically, but accepted uncritically, but conflicting new evidence is conflicting new evidence is brushed aside and not brushed aside and not reported because it does not reported because it does not fit, then that particular fit, then that particular science is in deep trouble—science is in deep trouble—and it has happened quite and it has happened quite often in the historical past.” often in the historical past.”
Be Aware of Cow DungBe Aware of Cow Dung
CoConventionnventional al
WWisdom isdom
of of
the the
DDomiominnant ant
GGrouproup
Always Be Skeptical: Even Babe Ruth Always Be Skeptical: Even Babe Ruth Only Got it Right at Bat 34% of the Only Got it Right at Bat 34% of the
TimeTime
Babe Ruth’s Lifetime Batting Average: 0.342Babe Ruth’s Lifetime Batting Average: 0.342
The Mitochondrion is the Organelle The Mitochondrion is the Organelle Involved in RespirationInvolved in Respiration
• By the end of the nineteenth By the end of the nineteenth century, it became clear that century, it became clear that respiration was a cellular respiration was a cellular processprocess that took place in that took place in almost each and every cell. almost each and every cell.
• Soon after, centrifugation showed Soon after, centrifugation showed that the uptake of oxygen was that the uptake of oxygen was associated with particles and associated with particles and subsequent structural studies subsequent structural studies showed that the showed that the mitochondrion mitochondrion was the respiratory organelle.was the respiratory organelle.
• MitosMitos is Greek for thread, and is Greek for thread, and chondrinchondrin is Greek for small grain. is Greek for small grain.
The German Dye IndustryThe German Dye Industry
Mitochondria Can Be Stained Mitochondria Can Be Stained With Fabric DyesWith Fabric Dyes
• At the suggestion of Paul At the suggestion of Paul Ehrlich, Leonor Michaelis Ehrlich, Leonor Michaelis (1900) tested the ability of (1900) tested the ability of the various newly-invented the various newly-invented fabric dyesfabric dyes to stain living to stain living tissue. tissue.
• Michaelis showed that the Michaelis showed that the mitochondria in pancreatic mitochondria in pancreatic exocrine cells could be exocrine cells could be selectively and vitally stained selectively and vitally stained with a dilute solution of one with a dilute solution of one of these dyes, of these dyes, Janus greenJanus green. .
Staining is only transient because the mitochondria Staining is only transient because the mitochondria reducereduce the dye and render it colorless. The ability of the dye and render it colorless. The ability of mitochondria to mitochondria to oxidizeoxidize and and reduce reduce various dyes was various dyes was what led Kingbury (1912) to propose that the what led Kingbury (1912) to propose that the mitochondriamitochondria may be involved in may be involved in cellular respirationcellular respiration. .
Glucose: A Condensation Glucose: A Condensation of Six Formaldehydes (CHof Six Formaldehydes (CH220)0)
The Discovery of GlycolysisThe Discovery of GlycolysisGlyco-lysis: the Breakdown of Glyco-lysis: the Breakdown of
SugarSugar
FermentatioFermentation has been used as a Food Processing n has been used as a Food Processing Technique throughout the World to Preserve and Flavor Technique throughout the World to Preserve and Flavor
Food for Thousands of YearsFood for Thousands of Years
• AlcoholAlcohol• WineWine• VinegarVinegar• OlivesOlives• Corned Corned
BeefBeef• BreadBread• SourdoughSourdough• SauerkrautSauerkraut• NattoNatto• Soy SauceSoy Sauce
•TeaTea•SakeSake•BeerBeer•CheeseCheese•PicklesPickles•KimchiKimchi•KefirKefir•SalamiSalami•ProsciuttProsciuttoo•YogurtYogurt
Louis Pasteur Guessed that Louis Pasteur Guessed that Fermentation is Respiration without Fermentation is Respiration without
Air, and it Required Living OrganismsAir, and it Required Living Organisms"I am of the opinion "I am of the opinion that alcoholic that alcoholic fermentation never fermentation never occurs without occurs without simultaneous simultaneous organization, organization, development and development and multiplication of multiplication of cells.... If asked, in cells.... If asked, in what consists the what consists the chemical act whereby chemical act whereby the sugar is the sugar is decomposed ... I am decomposed ... I am completely ignorant completely ignorant of it."of it."
Pasteur Had Trouble Convincing People Pasteur Had Trouble Convincing People that Fermentation was a Complex that Fermentation was a Complex
ProcessProcess
““Ah, you insist on thinking of alcoholic Ah, you insist on thinking of alcoholic fermentation as a simple breaking up fermentation as a simple breaking up of sugar into alcohol and carbonic of sugar into alcohol and carbonic acid! Undeceive yourselves…. Ah! So acid! Undeceive yourselves…. Ah! So you are bound to ignore the yeast in you are bound to ignore the yeast in this phenomenon, or at the most will this phenomenon, or at the most will concede to it only the role of initiator! concede to it only the role of initiator! Very well! Learn that this yeast Very well! Learn that this yeast always borrows something from the always borrows something from the sugar, and makes a part of its own sugar, and makes a part of its own tissues out of this food. Learn also tissues out of this food. Learn also that it is only on the condition of that it is only on the condition of keeping a little of the sugar for itself, keeping a little of the sugar for itself, that it consents to give you the rest in that it consents to give you the rest in the form of alcoholthe form of alcohol.”.”
Louis Pasteur Did Not Get Louis Pasteur Did Not Get Everything RightEverything Right• Whole yeast could Whole yeast could
ferment a sugar ferment a sugar solution.solution.
• Louis Pasteur Louis Pasteur (1879) tried but (1879) tried but was unable to get was unable to get ground up yeast to ground up yeast to ferment a sugar ferment a sugar solution.solution.
• He declared that He declared that fermentation was a fermentation was a vital action that vital action that required living required living cellscells. .
Fermentation Can Occur Fermentation Can Occur in in vitrovitro
• Eduard Buchner (1897) using a Eduard Buchner (1897) using a German beer yeastGerman beer yeast instead of instead of a a French wine yeastFrench wine yeast was able was able to obtain fermentation to obtain fermentation in vitroin vitro when he added sugar to a yeast when he added sugar to a yeast extract. extract.
• Actually this was a Actually this was a luckylucky find, find, since Buchner had no interest in since Buchner had no interest in glycolysis. He was making a glycolysis. He was making a health tonic, and only added the health tonic, and only added the sugar as a preservative, when sugar as a preservative, when the other antiseptics failed to the other antiseptics failed to keep the extract sterile.keep the extract sterile.
Origin of the Word: EnzymeOrigin of the Word: Enzyme
• Buchner named the Buchner named the extract zymase, extract zymase, from from zymezyme, the , the Greek word for Greek word for yeast, and yeast, and diastasisdiastasis, the Greek , the Greek word for break apart. word for break apart.
• Willy Kühne named Willy Kühne named all biocatalysts, all biocatalysts, enzymesenzymes, from the , from the Greek words, Greek words, en en zymezyme, which mean , which mean ““in yeastin yeast”. ”.
Fermentation in Yeast Involves Fermentation in Yeast Involves Many StepsMany Steps
• Unlike the burning of Unlike the burning of wood, the cellular wood, the cellular oxidation of glucose that oxidation of glucose that occurs at occurs at ambient ambient temperaturestemperatures depends depends on the intervention of on the intervention of enzymesenzymes and takes place and takes place in about a dozen in about a dozen sequential steps. sequential steps.
• This leads to the This leads to the production of many production of many intermediates intermediates and thus and thus cellular respiration is also cellular respiration is also known as intermediary known as intermediary metabolism. metabolism.
Fermentation and Glycolysis in Fermentation and Glycolysis in Muscle are Almost Identical Muscle are Almost Identical
ProcessesProcesses
It was astonishing for It was astonishing for the biochemists studying the biochemists studying fermentation in yeast fermentation in yeast and bacteria and bacteria or or glycolysis in muscleglycolysis in muscle that the chemistry of that the chemistry of these seemingly diverse these seemingly diverse processes, which take processes, which take place in different place in different kingdoms, were almost kingdoms, were almost identical.identical.
Discovering Biochemical Discovering Biochemical PathwaysPathways
• The studies of glycolysis and The studies of glycolysis and fermentation opened up an fermentation opened up an entirely new way of doing entirely new way of doing chemistry. Prior to these studies, chemistry. Prior to these studies, chemicals were chemicals were isolatedisolated from from cells but attempts to define their cells but attempts to define their relationshiprelationship in the cell were in the cell were rebuked with the words, rebuked with the words, “More “More matter with less art.”matter with less art.”
• Feeling that it was time to say, Feeling that it was time to say, “Enough matter, more art”,“Enough matter, more art”, biochemists, including Arthur biochemists, including Arthur Harden, Gustav Embden, Otto Harden, Gustav Embden, Otto Myerhof (1924) and Jacob Myerhof (1924) and Jacob Parnas (1910) began to piece Parnas (1910) began to piece together the together the biochemical biochemical pathwayspathways that occur in living that occur in living cells.cells.
Elucidating a Biochemical Elucidating a Biochemical PathwayPathway
• How could they determine the How could they determine the components and sequence of components and sequence of the pathway in the days the pathway in the days before radioactive isotopes? before radioactive isotopes?
• They found They found poisonspoisons that were that were inhibitors inhibitors of COof CO22 evolution. evolution.
• Then they determined which Then they determined which intermediates intermediates accumulated accumulated after treatment with the after treatment with the inhibitor. inhibitor.
• The chemical whose The chemical whose concentration concentration increasedincreased, after , after treatment with an inhibitor, treatment with an inhibitor, was presumably the was presumably the intermediate intermediate produced just produced just prior to the step blocked by prior to the step blocked by the inhibitor. the inhibitor.
Elucidating a Biochemical Elucidating a Biochemical PathwayPathway
A A → → B B →→ C C →→ D D →→ E E →→ F F →→ G G
Which intermediate would build up Which intermediate would build up first if I added a chemical that first if I added a chemical that inhibited the enzyme that converts E inhibited the enzyme that converts E to F?to F?
Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings
Figure 6.7C Details of glycolysis
NADH
ATP
Glucose PREPARATORY PHASE (energy investment)
Glucose-6-phosphate
Fructose-6-phosphate
Fructose-1,6-diphosphate
ATP
ADP
ADP
Step1
2
3
4
5
6
7
8
9
5
6
7
8
9
Pyruvate
ATP
ADP
P
P
P
PP
P
PPP P
P P
P P
P P
ATP
ADP
H2O H2O
ATP ATP
ADP ADP
Glyceraldehyde-3-phosphate(G3P)
ENERGY PAYOFF PHASE
1,3-Diphosphoglycerate
3-Phosphoglycerate
2-Phosphoglycerate
Phosphoenolpyruvate(PEP)
NAD NAD
NADHP
+H
1 3
4
5
6 9
Steps – A fuel molecule is energized, using ATP.
Step A six-carbon intermediate splits into two three-carbon intermediates.
Step A redox reaction generates NADH.
Steps – ATP and pyruvateare produced.
+H
P
In the Absence of Oxygen, the NADH In the Absence of Oxygen, the NADH Must Be Recycled or ATP Formation Must Be Recycled or ATP Formation
will not be Sustainablewill not be Sustainable
• In muscle, NADH is recycled to In muscle, NADH is recycled to NADNAD++ in the process of in the process of converting converting pyruvic acidpyruvic acid to to lactic acidlactic acid. The net yield from . The net yield from the oxidation of each glucose is the oxidation of each glucose is 2 ATP2 ATP..
• In yeast, NADH is recycled to In yeast, NADH is recycled to NADNAD++ in the process of in the process of converting converting pyruvic acidpyruvic acid to to ethanolethanol. The net yield from the . The net yield from the oxidation of each glucose is oxidation of each glucose is 2 2 ATPATP..
Anaerobic Respiration in Muscle Anaerobic Respiration in Muscle
and Yeastand Yeast
The Discovery of the Citric The Discovery of the Citric Acid (Krebs) CycleAcid (Krebs) Cycle
Aerobic Glycolysis Aerobic Glycolysis In the presence of oxygen, In the presence of oxygen, glucose glucose is is eventually split (lysed) into eventually split (lysed) into two pyruvic acids,two pyruvic acids, which means that only 2 out of 6 of the which means that only 2 out of 6 of the formaldehydes formaldehydes (HCOH)(HCOH) that make up the that make up the glucose were oxidized during glycolysis. glucose were oxidized during glycolysis. Additional energyAdditional energy can be obtained by the can be obtained by the oxidation of pyruvic acidoxidation of pyruvic acid. But how?. But how?
How are the Pyruvic Acids Produced in How are the Pyruvic Acids Produced in Glycolysis Burned to Produce Additional Glycolysis Burned to Produce Additional
Energy?Energy?
After courageously escaping the Nazis with the After courageously escaping the Nazis with the help of Albert Szent-Gyorgyi in 1933, Hans Krebs help of Albert Szent-Gyorgyi in 1933, Hans Krebs tackled the problem of how pyruvate is oxidized tackled the problem of how pyruvate is oxidized to carbon dioxide and water and was prepared to to carbon dioxide and water and was prepared to look for a look for a cyclecycle..
Cycles (in Life and Biology) Cycles (in Life and Biology) Facilitate Regulation and Facilitate Regulation and
Integration Integration • While he was in While he was in
Germany, Hans Krebs Germany, Hans Krebs had determined that in had determined that in the liver, urea is the liver, urea is synthesized from carbon synthesized from carbon dioxide and ammonia in dioxide and ammonia in a a cycliccyclic, not a , not a linear linear reaction. reaction.
• Compared with a linear Compared with a linear pathway, a pathway, a cyclecycle allows allows better better regulationregulation and and integration integration with the with the whole cell. whole cell.
Krebs Showed Pyruvic Acid Was Krebs Showed Pyruvic Acid Was “Burned” in a Cycle Too“Burned” in a Cycle Too
• Krebs found that a Krebs found that a number of organic acids, number of organic acids, including citric acid including citric acid stimulated stimulated OO22 uptake uptake in in muscle and liver.muscle and liver.
• He also found that in the He also found that in the presence of NAD tiny presence of NAD tiny (catalytic)(catalytic) amounts of amounts of these organic acids these organic acids stimulated the stimulated the oxidation oxidation of large of large quantities of quantities of pyruvic pyruvic acidacid..
Pyruvic acid
Krebs Showed Pyruvic Acid Was Krebs Showed Pyruvic Acid Was “Burned” in a Cycle“Burned” in a Cycle
• The presence of The presence of malonate, an malonate, an inhibitorinhibitor of succinic of succinic acid oxidation, results acid oxidation, results in the build up of in the build up of succinic acid no succinic acid no matter which matter which intermediate is added.intermediate is added.
• These data indicated These data indicated that the intermediates that the intermediates are arranged in a are arranged in a cyclecycle..
Krebs Showed Pyruvic Acid Was Krebs Showed Pyruvic Acid Was “Burned” in a Cycle“Burned” in a Cycle
• The presence of The presence of malonate, an malonate, an inhibitorinhibitor of succinic of succinic acid oxidation, results acid oxidation, results in the build up of in the build up of succinic acid no succinic acid no matter which matter which intermediate is added.intermediate is added.
• These data indicated These data indicated that the intermediates that the intermediates are arranged in a are arranged in a cyclecycle..
The Establishment Usually Takes Time The Establishment Usually Takes Time to Recognize the Work of a Prepared to Recognize the Work of a Prepared
MindMind• When Krebs first submitted his paper to the “premier When Krebs first submitted his paper to the “premier
journal”journal” Nature Nature, he got the following , he got the following rejection letterrejection letter::
"The editor of NATURE presents his compliments "The editor of NATURE presents his compliments to Dr. H. A. Krebs and regrets that as he has to Dr. H. A. Krebs and regrets that as he has already sufficient letters to fill the already sufficient letters to fill the correspondence column of NATURE for seven or correspondence column of NATURE for seven or eight weeks, it is undesirable to accept further eight weeks, it is undesirable to accept further letters at the present time…." letters at the present time…."
• Krebs then submitted his paper to the “second class Krebs then submitted his paper to the “second class journal” Enzymologia where it was accepted in 1937 journal” Enzymologia where it was accepted in 1937 and in 1953 Krebs won the Nobel Prize in Physiology of and in 1953 Krebs won the Nobel Prize in Physiology of Medicine for his work.Medicine for his work. nobelprize.org
Hans Krebs on His CycleHans Krebs on His Cycle
Vitamins B1- and B3-Vitamins B1- and B3-dependent conversion of dependent conversion of pyruvic acid to acetyl CoApyruvic acid to acetyl CoA
A biochemical lesion results because the above step does not occur
when Vitamins B1 or B3 are missing.
Nutrition: The B vitamins are Nutrition: The B vitamins are Necessary for Energy Necessary for Energy
MetabolismMetabolism• Every cell requires Every cell requires NiacinNiacin (vitamin (vitamin
B3B3), which is an essential component ), which is an essential component of of NADNAD, a cofactor in , a cofactor in anaerobic anaerobic and and aerobic aerobic energy metabolism. energy metabolism.
• Cells that use Cells that use aerobicaerobic energy energy metabolism also require metabolism also require ThiamineThiamine (vitamin (vitamin B1B1), which is an essential ), which is an essential part of a coenzyme required for part of a coenzyme required for aerobic energy metabolism. aerobic energy metabolism.
• Some cells are Some cells are more sensitivemore sensitive to a to a deficiencydeficiency in a given nutrient than in a given nutrient than others, which is why others, which is why diseases diseases caused by nutrient deficiencies show caused by nutrient deficiencies show up in a particular organ, tissue or cell up in a particular organ, tissue or cell type. type.
Beriberi (Paralysis Due to Beriberi (Paralysis Due to Damaged Nerves) and Pellagra Damaged Nerves) and Pellagra
(4Ds: Dermatitis, Diarrhea, (4Ds: Dermatitis, Diarrhea, Dementia, and Early Death)Dementia, and Early Death)
Biochemical Lesion: Nature and Biochemical Lesion: Nature and NurtureNurture
• Pyruvic acid must be activated before it Pyruvic acid must be activated before it can enter the Krebs cycle. can enter the Krebs cycle.
• The enzyme that catalyzes this The enzyme that catalyzes this activation step requires activation step requires thiaminthiamin pyrophosphate (TPP), a coenzyme pyrophosphate (TPP), a coenzyme derived from derived from vitamin B1vitamin B1..
• A deficiency in vitamin B1 results in an A deficiency in vitamin B1 results in an “environmentally-induced” “environmentally-induced” ““biochemical lesionbiochemical lesion”, a term coined by ”, a term coined by Rudolph Peters (Rudolph Peters (). ).
• The inability to perform a certain step in The inability to perform a certain step in a pathway may also be due to a a pathway may also be due to a deficiency in an enzyme involved in deficiency in an enzyme involved in catalyzing that step. According to catalyzing that step. According to Archibald Garrod (Archibald Garrod ()), this may be due , this may be due to an inborn error in metabolism, i.e. a to an inborn error in metabolism, i.e. a genetic lesion.genetic lesion.
The Discovery of the ElectronThe Discovery of the Electron Transport Chain and Oxidative Transport Chain and Oxidative
PhosphorylationPhosphorylation
The NADH Produced By the Krebs The NADH Produced By the Krebs Cycle Must Be OxidizedCycle Must Be Oxidized
• The Krebs cycle itself does not require The Krebs cycle itself does not require oxygen nor generate much energy in oxygen nor generate much energy in the form of ATP since the the form of ATP since the NADHNADH contains much of the original energy of contains much of the original energy of the glucose molecule. the glucose molecule.
• The NADH must be oxidized by the The NADH must be oxidized by the electron transport chainelectron transport chain. .
• At body temperature, oxygen does not At body temperature, oxygen does not directly attack NADH so how does the directly attack NADH so how does the oxygen act?oxygen act?
• It seemed likely that the catalyst would It seemed likely that the catalyst would contain contain ironiron, which has a high affinity , which has a high affinity for oxygen, and is able to bind it for oxygen, and is able to bind it reversibly. Think of rust, which is iron reversibly. Think of rust, which is iron oxide.oxide.
Discovery of the Electron Transport Discovery of the Electron Transport ChainChain
• In the mid 1800’s it was widely held In the mid 1800’s it was widely held that the blood was involved in that the blood was involved in respiration and indeed an respiration and indeed an iron-iron-containing containing compound was present in compound was present in the blood and is called the blood and is called hemoglobinhemoglobin..
• The concentration of iron in the blood The concentration of iron in the blood is so high that the French nobility is so high that the French nobility wore rings made from the iron wore rings made from the iron extracted from the blood of their extracted from the blood of their friends as a keepsake much like friends as a keepsake much like people wear a lock of a loved one’s people wear a lock of a loved one’s hair in a ring around their finger or in hair in a ring around their finger or in a locket around their neck. a locket around their neck.
Discovery of the Electron Discovery of the Electron Transport ChainTransport Chain
• In the 1850's Claude Bernard In the 1850's Claude Bernard realized that the realized that the color of color of the bloodthe blood depended on its depended on its state of oxygenation.state of oxygenation.
• George Gabriel Stokes George Gabriel Stokes (1864) concluded that (1864) concluded that hemoglobin exists in hemoglobin exists in oxidized (bright reddish) and oxidized (bright reddish) and reduced states (muddy dark reduced states (muddy dark red), and these can be red), and these can be distinguished by their distinguished by their absorption spectra. absorption spectra.
• A blood oxygen meter A blood oxygen meter measures the color of blood.measures the color of blood.
Oxygenated Blood Reflects Bright Red.Oxygenated Blood Reflects Bright Red.Deoxygenated and Carbonmonoxide-containing Deoxygenated and Carbonmonoxide-containing
Blood Reflects Blue and Red and Looks Dark Blood Reflects Blue and Red and Looks Dark Purplish.Purplish.
• Deoxygenated- and Deoxygenated- and carbonmonoxy-hemoglobin carbonmonoxy-hemoglobin absorb less and absorb less and reflect more reflect more blueblue (400-500 nm) and thus (400-500 nm) and thus appears bluer than appears bluer than oxygenated hemoglobin.oxygenated hemoglobin.
• Deoxygenated- and Deoxygenated- and carbonmonoxy- hemoglobin carbonmonoxy- hemoglobin absorb more red (600-650 nm) absorb more red (600-650 nm) and and reflect less red reflect less red which which makes it appear less red than makes it appear less red than oxygenated hemoglobin.oxygenated hemoglobin.
• The bright blue color of the The bright blue color of the veins depends on the veins depends on the optical optical properties of the skinproperties of the skin as as well as the purplish color of well as the purplish color of the blood within them.the blood within them.
Blue Green Red
Discovery of CytochromesDiscovery of Cytochromes
• After the general acceptance that After the general acceptance that respiration was a respiration was a cellularcellular phenomenon and not one that phenomenon and not one that occurred only in the blood, Charles occurred only in the blood, Charles MacMumm (1886) searched for MacMumm (1886) searched for respiratory pigments in many animal respiratory pigments in many animal tissues. tissues.
• He found a He found a pigmentpigment whose whose absorption spectrumabsorption spectrum varied with its varied with its oxidation stateoxidation state—just like —just like hemoglobin. hemoglobin.
• David Keilin (1925) showed that this David Keilin (1925) showed that this pigment was really a mixture of 3 pigment was really a mixture of 3 pigments which he named pigments which he named cytochromes a, b and c. cytochromes a, b and c. CytochromeCytochrome means “cell color”. means “cell color”.
• But none of these cytochromes But none of these cytochromes interacted directly with Ointeracted directly with O22..
The Discovery of the Iron-The Discovery of the Iron-Containing Enzyme (Cytochrome Containing Enzyme (Cytochrome
Oxidase) that Binds OxygenOxidase) that Binds Oxygen
• Otto Warburg, Hans Otto Warburg, Hans Krebs’ teacher and a Jew Krebs’ teacher and a Jew who accepted Hitler’s who accepted Hitler’s invitation to stay in invitation to stay in Germany as an honorary Germany as an honorary Aryan, discovered another Aryan, discovered another cytochrome, called cytochrome, called cytochrome oxidasecytochrome oxidase that directly binds Othat directly binds O22..
• Carbon monoxideCarbon monoxide and and cyanidecyanide cause death by cause death by inhibiting the action of inhibiting the action of this protein.this protein.
Discovery that the Mitochondrial Discovery that the Mitochondrial Electron Transport Chain Converts Electron Transport Chain Converts
the Energy in NADH into the the Energy in NADH into the Energy in ATPEnergy in ATP
• Albert Lehninger showed Albert Lehninger showed that that ATP is formedATP is formed when when NADH NADH is given to isolated is given to isolated mitochondriamitochondria. .
• The complete combustion The complete combustion of glucose in the presence of glucose in the presence of Oof O22 yields approximately yields approximately 38 ATPs38 ATPs (compared to (compared to 2 2 ATPsATPs obtained by glycolysis obtained by glycolysis in the absence of oxygen).in the absence of oxygen).
Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings
Figure 6.10 Oxidative phosphorylation, using electron transport and chemiosmosis in the mitochondrion
Intermembrane space
Inner mitochondrial membrane
Mitochondrial matrix
Protein complex
Electron flow
Electron carrier
NADH NAD+
FADH2 FAD
H2OATPADP
ATP synthase
H+ H+ H+
H+
H+H+
H+
H+
H+
H+
H+
H+
H+
H+
P
1
2O2
Electron Transport Chain Chemiosmosis
.
OXIDATIVE PHOSPHORYLATION
+ 2
A Summary of Cellular A Summary of Cellular RespirationRespiration
ATP is Used as an Energy ATP is Used as an Energy Source for:Source for:
• Synthesizing carbohydratesSynthesizing carbohydrates (dehydrations)(dehydrations)
• Synthesizing DNA and RNASynthesizing DNA and RNA (dehydrations) (dehydrations)• Synthesizing proteinsSynthesizing proteins (dehydrations) (dehydrations)• Synthesizing lipidsSynthesizing lipids (dehydrations) (dehydrations)• Synthesizing coenzymesSynthesizing coenzymes (e.g. NAD) (e.g. NAD)• Transporting substances across Transporting substances across
membranesmembranes• SecretionSecretion• Cell motility: muscle movementCell motility: muscle movement• Nearly everything…Nearly everything…
Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings
Figure 6.3 Summary equation for cellular respiration
C6H12O6 CO26 H2O ATPs
Glucose Oxygen gas Carbon dioxide
6
Water Energy
O2 6+ + +
Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings
When you eat and breathe, you make cellular respiration possible.
CO2
CO2
O2
O2Bloodstream
Muscle cells carrying out
Cellular Respiration
Breathing
Glucose O2
CO2 H2O ATP
Lungs
Science Songs