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Hemoglobin and the Movement of Oxygen
Hemoglobin and the Movement of Oxygen• Introduction
Hemoglobin and the Movement of Oxygen• Introduction
Animals Have Widely Varying Needs for OxygenDemand for Oxygen Can Change in SecondsBasal Needs are Significant - Diffusion not Enough
Hemoglobin and the Movement of Oxygen• Introduction
Animals Have Widely Varying Needs for OxygenDemand for Oxygen Can Change in SecondsBasal Needs are Significant - Diffusion not EnoughExercise, Fight/Flight Add to the Need
Hemoglobin and the Movement of Oxygen• Introduction
Animals Have Widely Varying Needs for OxygenDemand for Oxygen Can Change in SecondsBasal Needs are Significant - Diffusion not EnoughExercise, Fight/Flight Add to the NeedATP Energy Produced Aerobically 15 Times More Efficiently Than Anaerobically
Hemoglobin and the Movement of Oxygen• Introduction
Animals Have Widely Varying Needs for OxygenDemand for Oxygen Can Change in SecondsBasal Needs are Significant - Diffusion not EnoughExercise, Fight/Flight Add to the NeedATP Energy Produced Aerobically 15 Times More Efficiently Than Anaerobically
Respiration versus Fermentation
Hemoglobin and the Movement of Oxygen• Introduction
Animals Have Widely Varying Needs for OxygenDemand for Oxygen Can Change in SecondsBasal Needs are Significant - Diffusion not EnoughExercise, Fight/Flight Add to the NeedATP Energy Produced Aerobically 15 Times More Efficiently Than Anaerobically
Respiration versus FermentationEfficient, Adaptable Oxygen Delivery is Necessary
Quaternary Structure• Interaction of multiple protein subunits
Quaternary Structure• Interaction of multiple protein subunits
Hemoglobin - 4 Subunits (α2β2), 1 Heme Each, 1 O2 Each, 1 “Donut Hole”Myoglobin - 1 Subunit, 1 Heme, 1 O2 Each
Quaternary Structure• Interaction of multiple protein subunits
Hemoglobin - 4 Subunits (α2β2), 1 Heme Each, 1 O2 Each, 1 “Donut Hole”Myoglobin - 1 Subunit, 1 Heme, 1 O2 Each
Quaternary Structure• Interaction of multiple protein subunits
Hemoglobin - 4 Subunits (α2β2), 1 Heme Each, 1 O2 Each, 1 “Donut Hole”Myoglobin - 1 Subunit, 1 Heme, 1 O2 Each
Quaternary Structure• Interaction of multiple protein subunits
Hemoglobin - 4 Subunits (α2β2), 1 Heme Each, 1 O2 Each, 1 “Donut Hole”Myoglobin - 1 Subunit, 1 Heme, 1 O2 Each
Quaternary Structure• Interaction of multiple protein subunits
Hemoglobin - 4 Subunits (α2β2), 1 Heme Each, 1 O2 Each, 1 “Donut Hole”Myoglobin - 1 Subunit, 1 Heme, 1 O2 Each
Quaternary Structure• Interaction of multiple protein subunits
Hemoglobin - 4 Subunits (α2β2), 1 Heme Each, 1 O2 Each, 1 “Donut Hole”Myoglobin - 1 Subunit, 1 Heme, 1 O2 Each
Quaternary Structure• Interaction of multiple protein subunits
Hemoglobin - 4 Subunits (α2β2), 1 Heme Each, 1 O2 Each, 1 “Donut Hole”Myoglobin - 1 Subunit, 1 Heme, 1 O2 Each
Quaternary Structure• Interaction of multiple protein subunits
Hemoglobin - 4 Subunits (α2β2), 1 Heme Each, 1 O2 Each, 1 “Donut Hole”Myoglobin - 1 Subunit, 1 Heme, 1 O2 Each
Quaternary Structure• Interaction of multiple protein subunits
Hemoglobin - 4 Subunits (α2β2), 1 Heme Each, 1 O2 Each, 1 “Donut Hole”Myoglobin - 1 Subunit, 1 Heme, 1 O2 Each
Hemoglobin and the Movement of Oxygen• Structure and Function
Hemoglobin and the Movement of Oxygen• Structure and Function
Heme Prosthetic GroupFerrous Iron - Methemoglobin Won’t WorkOnly Fe++ Binds Oxygen
Hemoglobin and the Movement of Oxygen• Structure and Function
Hemoglobin and the Movement of Oxygen• Structure and Function
Edge-on View
Hemoglobin and the Movement of Oxygen• Structure and Function
Edge-on View
Attached to Remainder of Global Subunit
Hemoglobin and the Movement of Oxygen• Structure and Function
Edge-on View
Attached to Remainder of Global Subunit
Hemoglobin and the Movement of Oxygen• Structure and Function
Edge-on View
Attached to Remainder of Global Subunit
Histidine’s Movement Changes
Global Unit’s Shape
Hemoglobin and the Movement of Oxygen• Cooperativity
Exiting Lungs
Hemoglobin and the Movement of Oxygen• Cooperativity
Entering Lungs
Exiting Lungs
Hemoglobin and the Movement of Oxygen• Cooperativity
No Oxygen (T-State)
Entering Lungs
Exiting Lungs
Hemoglobin and the Movement of Oxygen• Cooperativity
No Oxygen (T-State)
Oxygen Bound
Entering Lungs
Exiting Lungs
Hemoglobin and the Movement of Oxygen• Cooperativity
No Oxygen (T-State)
Oxygen Bound
Affected by O2 Binding (R-State)
Entering Lungs
Exiting Lungs
Hemoglobin and the Movement of Oxygen• Cooperativity
No Oxygen (T-State)
Oxygen Bound Affected by O2 Binding
R-State
Affected by O2 Binding (R-State)
Entering Lungs
Exiting Lungs
Hemoglobin and the Movement of Oxygen• Cooperativity
No Oxygen (T-State)
Oxygen Bound Affected by O2 Binding
R-State
Affected by O2 Binding (R-State)
Entering Lungs
Exiting Lungs
Fully Oxygenated (R-State)
Hemoglobin and the Movement of Oxygen• Cooperativity
No Oxygen (T-State)
Oxygen Bound Affected by O2 Binding
R-State
Affected by O2 Binding (R-State)
Binding of the first O2 favors binding of second, etc. - CooperativelyCooperatively Important as Hemoglobin Rapidly Passes Through Lungs
Entering Lungs
Exiting Lungs
Fully Oxygenated (R-State)
Hemoglobin and the Movement of Oxygen• Cooperativity
Hemoglobin and the Movement of Oxygen• Cooperativity
At Low O2, Myoglobin Holds More than Hemoglobin
Hemoglobin and the Movement of Oxygen• Cooperativity
At Low O2, Myoglobin Holds More than Hemoglobin
Hemoglobin and the Movement of Oxygen• Cooperativity
At Low O2, Myoglobin Holds More than Hemoglobin
Hemoglobin and the Movement of Oxygen• Cooperativity
At Low O2, Myoglobin Holds More than Hemoglobin
At High O2, Both Hold 100%
Hemoglobin and the Movement of Oxygen• Cooperativity
At Low O2, Myoglobin Holds More than Hemoglobin
At High O2, Both Hold 100%
Hyperbolic Binding Curve
Hemoglobin and the Movement of Oxygen• Cooperativity
At Low O2, Myoglobin Holds More than Hemoglobin
At High O2, Both Hold 100%
Sigmoidal Binding Curve
Hyperbolic Binding Curve
Hemoglobin and the Movement of Oxygen• Cooperativity
At Low O2, Myoglobin Holds More than Hemoglobin
At High O2, Both Hold 100%
As Curves Move to Right Less Affinity for Oxygen
Hemoglobin and the Movement of Oxygen• Cooperativity
At Low O2, Myoglobin Holds More than Hemoglobin
At High O2, Both Hold 100%
Myoglobin Better for Storing OxygenHemoglobin Better at Delivering Oxygen
As Curves Move to Right Less Affinity for Oxygen
Hemoglobin and the Movement of Oxygen• Bohr Effect
Hemoglobin and the Movement of Oxygen• Bohr Effect
Less Oxygen Bound at Same Pressure
Hemoglobin and the Movement of Oxygen• Bohr Effect
Less Oxygen Bound at Same Pressure
More O2 Required To Have Same Fraction Bound
Hemoglobin and the Movement of Oxygen• Bohr Effect
More Affinity
Hemoglobin and the Movement of Oxygen• Bohr Effect
More Affinity
Less Affinity
Hemoglobin and the Movement of Oxygen• Bohr Effect
Protons Can Bind to HemoglobinProtons Change Hemoglobin’s Shape Reshaped Hemoglobin Loses Oxygen
Hemoglobin and the Movement of Oxygen• Bohr Effect
Protons Can Bind to HemoglobinProtons Change Hemoglobin’s Shape Reshaped Hemoglobin Loses Oxygen
Rapidly Metabolizing Tissues Release Protons
Hemoglobin and the Movement of Oxygen• Bohr Effect
Protons Can Bind to HemoglobinProtons Change Hemoglobin’s Shape Reshaped Hemoglobin Loses Oxygen
Rapidly Metabolizing Tissues Release ProtonsRapidly Metabolizing Tissues Get More Oxygen From Hemoglobin
Hemoglobin and the Movement of Oxygen• Bohr Effect & CO2
Hemoglobin and the Movement of Oxygen• Bohr Effect & CO2
Hemoglobin and the Movement of Oxygen• Bohr Effect & CO2
Acid Favors Release of O2 From HemoglobinCO2 Favors Release of O2 From Hemoglobin
Hemoglobin and the Movement of Oxygen• Bohr Effect & CO2
Acid Favors Release of O2 From HemoglobinCO2 Favors Release of O2 From Hemoglobin
Acid and CO2 are Released by Rapidly Metabolizing Tissues
Hemoglobin and the Movement of Oxygen• 2,3 BPG
2,3 Bisphosphoglycerate
Hemoglobin and the Movement of Oxygen• 2,3 BPG
2,3 Bisphosphoglycerate
Byproduct of GlycolysisExercising Muscle Cells Rapid Use GlycolysisExercising Muscle Cells Produce Acid, CO2, and 2,3 BPG
Hemoglobin and the Movement of Oxygen• 2,3 BPG
2,3 Bisphosphoglycerate
Byproduct of GlycolysisExercising Muscle Cells Rapid Use GlycolysisExercising Muscle Cells Produce Acid, CO2, and 2,3 BPGBinds in Hole of Donut
Hemoglobin and the Movement of Oxygen• 2,3 BPG
2,3 Bisphosphoglycerate
Byproduct of GlycolysisExercising Muscle Cells Rapid Use GlycolysisExercising Muscle Cells Produce Acid, CO2, and 2,3 BPGBinds in Hole of DonutLocks Hemoglobin in T-State
Hemoglobin and the Movement of Oxygen• 2,3 BPG and Oxygen Binding
Hemoglobin and the Movement of Oxygen• 2,3 BPG and Oxygen Binding
Slow Metabolic Rate
Hemoglobin and the Movement of Oxygen• 2,3 BPG and Oxygen Binding
Slow Metabolic Rate
Fast Metabolic Rate
Hemoglobin and the Movement of Oxygen• 2,3 BPG and Oxygen Binding
Hemoglobin and the Movement of Oxygen• 2,3 BPG and Oxygen Binding
Rapidly Metabolizing Cells Produce AcidRapidly Metabolizing Cells Release CO2
Hemoglobin and the Movement of Oxygen• 2,3 BPG and Oxygen Binding
Rapidly Metabolizing Cells Produce AcidRapidly Metabolizing Cells Release CO2
Rapidly Metabolizing Cells Release 2,3 BPG
Hemoglobin and the Movement of Oxygen• 2,3 BPG and Oxygen Binding
Rapidly Metabolizing Cells Produce AcidRapidly Metabolizing Cells Release CO2
Rapidly Metabolizing Cells Release 2,3 BPG
All Favor O2 Release from Hemoglobin
Hemoglobin and the Movement of Oxygen• 2,3 BPG and Oxygen Binding
Rapidly Metabolizing Cells Produce AcidRapidly Metabolizing Cells Release CO2
Rapidly Metabolizing Cells Release 2,3 BPG
All Favor O2 Release from Hemoglobin So
Hemoglobin and the Movement of Oxygen• 2,3 BPG and Oxygen Binding
Rapidly Metabolizing Cells Produce AcidRapidly Metabolizing Cells Release CO2
Rapidly Metabolizing Cells Release 2,3 BPG
All Favor O2 Release from Hemoglobin So
Rapidly Metabolizing Cells Get More O2
Hemoglobin and the Movement of Oxygen• 2,3 BPG and Smoking
2,3 Bisphosphoglycerate
Hemoglobin and the Movement of Oxygen• 2,3 BPG and Smoking
2,3 Bisphosphoglycerate
2,3 BPG Big Concern for SmokersBlood of Smokers has High Levels of 2,3 BPGHemoglobin Gets Locked in T-state in Passage Through Lungs
Hemoglobin and the Movement of Oxygen• 2,3 BPG and Smoking
2,3 Bisphosphoglycerate
2,3 BPG Big Concern for SmokersBlood of Smokers has High Levels of 2,3 BPGHemoglobin Gets Locked in T-state in Passage Through LungsOxygen Carrying Capacity of Blood Reduced
Hemoglobin and the Movement of Oxygen• 2,3 BPG and Smoking
2,3 Bisphosphoglycerate
2,3 BPG Big Concern for SmokersBlood of Smokers has High Levels of 2,3 BPGHemoglobin Gets Locked in T-state in Passage Through LungsOxygen Carrying Capacity of Blood ReducedCarbon Monoxide Levels Also Higher in Smokers
Hemoglobin and the Movement of Oxygen• Movement of CO2
Hemoglobin and the Movement of Oxygen• Movement of CO2
Rapidly Metabolizing Tissue
Hemoglobin and the Movement of Oxygen• Movement of CO2
Rapidly Metabolizing Tissue
HbO + H+ O2 Blood
Hemoglobin and the Movement of Oxygen• Movement of CO2
Rapidly Metabolizing Tissue
H+:Hb-CO2
HbO + H+ O2 Blood
Hemoglobin and the Movement of Oxygen• Movement of CO2
Rapidly Metabolizing Tissue Some
H+:Hb-CO2
HbO + H+ O2 Blood
Hemoglobin and the Movement of Oxygen• Movement of CO2
Rapidly Metabolizing Tissue Some
H+:Hb-CO2
RemainderH2O
Blood
HbO + H+ O2 Blood
Hemoglobin and the Movement of Oxygen• Movement of CO2
Rapidly Metabolizing Tissue Some
H+:Hb-CO2
RemainderH2O
Blood
HbO + H+ O2 Blood
H+:Hb-CO2
HbO
Hemoglobin and the Movement of Oxygen• Movement of CO2
Rapidly Metabolizing Tissue Some
LungsO2 + H+:Hb-CO2
H+:Hb-CO2
RemainderH2O
Blood
HbO + H+ O2 Blood
H+:Hb-CO2
HbO
Hemoglobin and the Movement of Oxygen• Movement of CO2
Rapidly Metabolizing Tissue Some
LungsO2 + H+:Hb-CO2
H+:Hb-CO2
RemainderH2O
Blood
HbO + H+ O2 Blood
H+:Hb-CO2
HbO HbO
Hemoglobin and the Movement of Oxygen• Movement of CO2
Rapidly Metabolizing Tissue Some
LungsO2 + H+:Hb-CO2
H+:Hb-CO2
RemainderH2O
Blood
HbO + H+ O2 Blood
H+:Hb-CO2
HbO HbO
Hemoglobin and the Movement of Oxygen• Movement of CO2
Rapidly Metabolizing Tissue Some
H2O + CO2 LungsO2 + H+:Hb-CO2
H+:Hb-CO2
RemainderH2O
Blood
HbO + H+ O2 Blood
H+:Hb-CO2
HbO HbO
Hemoglobin and the Movement of Oxygen• Movement of CO2
Rapidly Metabolizing Tissue Some
H2O + CO2 LungsO2 + H+:Hb-CO2
H+:Hb-CO2
RemainderH2O
Blood
HbO + H+ O2 Blood
H+:Hb-CO2
HbO HbOExhaled
Hemoglobin and the Movement of Oxygen• Carbon Monoxide and Heme
Hemoglobin and the Movement of Oxygen• Carbon Monoxide and Heme
An Additional Histidine is Present at the Heme Iron SiteReduces Affinity to CO, but Does Not Eliminate itCarbon Monoxide in Cigarette Smoke
Hemoglobin and the Movement of Oxygen• Carbon Monoxide and Heme
An Additional Histidine is Present at the Heme Iron SiteReduces Affinity to CO, but Does Not Eliminate itCarbon Monoxide in Cigarette SmokeNote That CO2 Does Not Bind to Heme, nor do Protons
Hemoglobin and the Movement of Oxygen• Fetal Hemoglobin
Hemoglobin and the Movement of Oxygen• Fetal Hemoglobin
The Body Makes Different Globins Over TimeMost Variations Centered on BirthFetal Hemoglobin Mostly α2γ2
Hemoglobin and the Movement of Oxygen• Fetal Hemoglobin
The Body Makes Different Globins Over TimeMost Variations Centered on BirthFetal Hemoglobin Mostly α2γ2
High Most of Life
Hemoglobin and the Movement of Oxygen• Fetal Hemoglobin
The Body Makes Different Globins Over TimeMost Variations Centered on BirthFetal Hemoglobin Mostly α2γ2
High Most of Life
Highest in Fetus
Hemoglobin and the Movement of Oxygen• Fetal Hemoglobin
The Body Makes Different Globins Over TimeMost Variations Centered on BirthFetal Hemoglobin Mostly α2γ2
High Most of Life
Highest in Fetus At Adult Levels by 24 Weeks
Hemoglobin and the Movement of Oxygen• Fetal Hemoglobin
Increasing Affinity
Fetal Hemoglobin Can’t Bind to 2,3 BPG Mostly Remains in R-state
Hemoglobin and the Movement of Oxygen• Sickle Cell Anemia
Hemoglobin and the Movement of Oxygen• Sickle Cell Anemia
Sickle Cell Anemia is a Genetic Disease Affecting HemoglobinMultiple Forms - Mutation of Glu to Val at Position #6 Most CommonRed Blood Cells Lose Rounded Shape and Form Sickles
Hemoglobin and the Movement of Oxygen• Sickle Cell Anemia
Sickle Cell Anemia is a Genetic Disease Affecting HemoglobinMultiple Forms - Mutation of Glu to Val at Position #6 Most CommonRed Blood Cells Lose Rounded Shape and Form SicklesShape Change Happens in Low O2 Conditions - Exercise
Hemoglobin and the Movement of Oxygen• Sickle Cell Anemia
Sickle Cell Anemia is a Genetic Disease Affecting HemoglobinMultiple Forms - Mutation of Glu to Val at Position #6 Most CommonRed Blood Cells Lose Rounded Shape and Form SicklesShape Change Happens in Low O2 Conditions - ExerciseChange Caused by Polymerization of Hemoglobin
Hemoglobin and the Movement of Oxygen• Sickle Cell Anemia
Sickle Cell Anemia is a Genetic Disease Affecting HemoglobinMultiple Forms - Mutation of Glu to Val at Position #6 Most CommonRed Blood Cells Lose Rounded Shape and Form SicklesShape Change Happens in Low O2 Conditions - ExerciseChange Caused by Polymerization of Hemoglobin
Sickled Cells
Hemoglobin and the Movement of Oxygen• Sickle Cell Anemia
Hemoglobin and the Movement of Oxygen• Sickle Cell Anemia
Rounded Cells Move Easily Through Capillaries
Sickled Cells Get Stuck
Hemoglobin and the Movement of Oxygen• Sickle Cell Anemia
Rounded Cells Move Easily Through Capillaries
Sickled Cells Get Stuck
Hemoglobin and the Movement of Oxygen• Sickle Cell Anemia
Rounded Cells Move Easily Through Capillaries
Sickled Cells Get StuckSickled Cells Removed by Spleen
Hemoglobin and the Movement of Oxygen• Sickle Cell Anemia
Hemoglobin and the Movement of Oxygen• Sickle Cell Anemia
Why is Sickle Cell Anemia so Widespread?Why Has it Not Been Selected Against?
Hemoglobin and the Movement of Oxygen• Sickle Cell Anemia
Why is Sickle Cell Anemia so Widespread?Why Has it Not Been Selected Against?
Hemoglobin and the Movement of Oxygen• Sickle Cell Anemia
Why is Sickle Cell Anemia so Widespread?Why Has it Not Been Selected Against?
Greatest Incidence of Sickle Cell Anemia
Hemoglobin and the Movement of Oxygen• Sickle Cell Anemia
Why is Sickle Cell Anemia so Widespread?Why Has it Not Been Selected Against?
Greatest Incidence of MalariaGreatest Incidence of Sickle Cell Anemia
Hemoglobin and the Movement of Oxygen• Sickle Cell Anemia
Why is Sickle Cell Anemia so Widespread?Why Has it Not Been Selected Against?
Greatest Incidence of MalariaGreatest Incidence of Sickle Cell Anemia
Hemoglobin and the Movement of Oxygen• Sickle Cell Anemia
Benefit of Sickle Cell Mutation for Heterozygotes No Benefit to Homozygous Recessive or Dominant
Hemoglobin and the Movement of Oxygen• Summary
Hemoglobin and the Movement of Oxygen• Summary
Animals Have Widely Varying O2 NeedsATP Generated Much More Efficiently in Presence of O2Hemoglobin and Myoglobin are Related, but Have Different Functions
Hemoglobin and the Movement of Oxygen• Summary
Animals Have Widely Varying O2 NeedsATP Generated Much More Efficiently in Presence of O2Hemoglobin and Myoglobin are Related, but Have Different FunctionsHemoglobin has Four Subunits and Hemes. Myoglobin has One of Each
Hemoglobin and the Movement of Oxygen• Summary
Animals Have Widely Varying O2 NeedsATP Generated Much More Efficiently in Presence of O2Hemoglobin and Myoglobin are Related, but Have Different FunctionsHemoglobin has Four Subunits and Hemes. Myoglobin has One of EachBind of O2 by Heme’s Iron Pulls up on a Histidine and Change’s Hemoglobin’s Shape
Hemoglobin and the Movement of Oxygen• Summary
Animals Have Widely Varying O2 NeedsATP Generated Much More Efficiently in Presence of O2Hemoglobin and Myoglobin are Related, but Have Different FunctionsHemoglobin has Four Subunits and Hemes. Myoglobin has One of EachBind of O2 by Heme’s Iron Pulls up on a Histidine and Change’s Hemoglobin’s ShapeChanging Hemoglobin’s Shape Converts Hemoglobin from T-state to R-state
Hemoglobin and the Movement of Oxygen• Summary
Animals Have Widely Varying O2 NeedsATP Generated Much More Efficiently in Presence of O2Hemoglobin and Myoglobin are Related, but Have Different FunctionsHemoglobin has Four Subunits and Hemes. Myoglobin has One of EachBind of O2 by Heme’s Iron Pulls up on a Histidine and Change’s Hemoglobin’s ShapeChanging Hemoglobin’s Shape Converts Hemoglobin from T-state to R-stateR-state Binds Oxygen Better. T-state Releases O2 Better
Hemoglobin and the Movement of Oxygen• Summary
Animals Have Widely Varying O2 NeedsATP Generated Much More Efficiently in Presence of O2Hemoglobin and Myoglobin are Related, but Have Different FunctionsHemoglobin has Four Subunits and Hemes. Myoglobin has One of EachBind of O2 by Heme’s Iron Pulls up on a Histidine and Change’s Hemoglobin’s ShapeChanging Hemoglobin’s Shape Converts Hemoglobin from T-state to R-stateR-state Binds Oxygen Better. T-state Releases O2 BetterIn the Bohr Effect, Binding of CO2 and H+ Favors O2 Release
Hemoglobin and the Movement of Oxygen• Summary
Animals Have Widely Varying O2 NeedsATP Generated Much More Efficiently in Presence of O2Hemoglobin and Myoglobin are Related, but Have Different FunctionsHemoglobin has Four Subunits and Hemes. Myoglobin has One of EachBind of O2 by Heme’s Iron Pulls up on a Histidine and Change’s Hemoglobin’s ShapeChanging Hemoglobin’s Shape Converts Hemoglobin from T-state to R-stateR-state Binds Oxygen Better. T-state Releases O2 BetterIn the Bohr Effect, Binding of CO2 and H+ Favors O2 ReleaseThe Bohr Effect Explains How Oxygen and CO2 Exchanged in Lungs
Hemoglobin and the Movement of Oxygen• Summary
Animals Have Widely Varying O2 NeedsATP Generated Much More Efficiently in Presence of O2Hemoglobin and Myoglobin are Related, but Have Different FunctionsHemoglobin has Four Subunits and Hemes. Myoglobin has One of EachBind of O2 by Heme’s Iron Pulls up on a Histidine and Change’s Hemoglobin’s ShapeChanging Hemoglobin’s Shape Converts Hemoglobin from T-state to R-stateR-state Binds Oxygen Better. T-state Releases O2 BetterIn the Bohr Effect, Binding of CO2 and H+ Favors O2 ReleaseThe Bohr Effect Explains How Oxygen and CO2 Exchanged in Lungs2,3 BPG is Produced by Rapidly Metabolizing Cells. It too Favors O2 Release
Hemoglobin and the Movement of Oxygen• Summary
Animals Have Widely Varying O2 NeedsATP Generated Much More Efficiently in Presence of O2Hemoglobin and Myoglobin are Related, but Have Different FunctionsHemoglobin has Four Subunits and Hemes. Myoglobin has One of EachBind of O2 by Heme’s Iron Pulls up on a Histidine and Change’s Hemoglobin’s ShapeChanging Hemoglobin’s Shape Converts Hemoglobin from T-state to R-stateR-state Binds Oxygen Better. T-state Releases O2 BetterIn the Bohr Effect, Binding of CO2 and H+ Favors O2 ReleaseThe Bohr Effect Explains How Oxygen and CO2 Exchanged in Lungs2,3 BPG is Produced by Rapidly Metabolizing Cells. It too Favors O2 ReleaseFetal Hemoglobin Can’t Bind 2,3 BPG and has Greater O2 Affinity Than Adult Hemoglobin
Hemoglobin and the Movement of Oxygen• Summary
Animals Have Widely Varying O2 NeedsATP Generated Much More Efficiently in Presence of O2Hemoglobin and Myoglobin are Related, but Have Different FunctionsHemoglobin has Four Subunits and Hemes. Myoglobin has One of EachBind of O2 by Heme’s Iron Pulls up on a Histidine and Change’s Hemoglobin’s ShapeChanging Hemoglobin’s Shape Converts Hemoglobin from T-state to R-stateR-state Binds Oxygen Better. T-state Releases O2 BetterIn the Bohr Effect, Binding of CO2 and H+ Favors O2 ReleaseThe Bohr Effect Explains How Oxygen and CO2 Exchanged in Lungs2,3 BPG is Produced by Rapidly Metabolizing Cells. It too Favors O2 ReleaseFetal Hemoglobin Can’t Bind 2,3 BPG and has Greater O2 Affinity Than Adult HemoglobinSickle Cell Anemia (SCA) is a Genetic Disease of Hemoglobin
Hemoglobin and the Movement of Oxygen• Summary
Animals Have Widely Varying O2 NeedsATP Generated Much More Efficiently in Presence of O2Hemoglobin and Myoglobin are Related, but Have Different FunctionsHemoglobin has Four Subunits and Hemes. Myoglobin has One of EachBind of O2 by Heme’s Iron Pulls up on a Histidine and Change’s Hemoglobin’s ShapeChanging Hemoglobin’s Shape Converts Hemoglobin from T-state to R-stateR-state Binds Oxygen Better. T-state Releases O2 BetterIn the Bohr Effect, Binding of CO2 and H+ Favors O2 ReleaseThe Bohr Effect Explains How Oxygen and CO2 Exchanged in Lungs2,3 BPG is Produced by Rapidly Metabolizing Cells. It too Favors O2 ReleaseFetal Hemoglobin Can’t Bind 2,3 BPG and has Greater O2 Affinity Than Adult HemoglobinSickle Cell Anemia (SCA) is a Genetic Disease of HemoglobinIn Low O2 Concentration, Red Blood Cells of SCA Sufferers Form Sickle Shapes
Hemoglobin and the Movement of Oxygen• Summary
Animals Have Widely Varying O2 NeedsATP Generated Much More Efficiently in Presence of O2Hemoglobin and Myoglobin are Related, but Have Different FunctionsHemoglobin has Four Subunits and Hemes. Myoglobin has One of EachBind of O2 by Heme’s Iron Pulls up on a Histidine and Change’s Hemoglobin’s ShapeChanging Hemoglobin’s Shape Converts Hemoglobin from T-state to R-stateR-state Binds Oxygen Better. T-state Releases O2 BetterIn the Bohr Effect, Binding of CO2 and H+ Favors O2 ReleaseThe Bohr Effect Explains How Oxygen and CO2 Exchanged in Lungs2,3 BPG is Produced by Rapidly Metabolizing Cells. It too Favors O2 ReleaseFetal Hemoglobin Can’t Bind 2,3 BPG and has Greater O2 Affinity Than Adult HemoglobinSickle Cell Anemia (SCA) is a Genetic Disease of HemoglobinIn Low O2 Concentration, Red Blood Cells of SCA Sufferers Form Sickle ShapesSickled Cells Stick in Capillaries and Can be Fatal
Hemoglobin and the Movement of Oxygen• Summary
Animals Have Widely Varying O2 NeedsATP Generated Much More Efficiently in Presence of O2Hemoglobin and Myoglobin are Related, but Have Different FunctionsHemoglobin has Four Subunits and Hemes. Myoglobin has One of EachBind of O2 by Heme’s Iron Pulls up on a Histidine and Change’s Hemoglobin’s ShapeChanging Hemoglobin’s Shape Converts Hemoglobin from T-state to R-stateR-state Binds Oxygen Better. T-state Releases O2 BetterIn the Bohr Effect, Binding of CO2 and H+ Favors O2 ReleaseThe Bohr Effect Explains How Oxygen and CO2 Exchanged in Lungs2,3 BPG is Produced by Rapidly Metabolizing Cells. It too Favors O2 ReleaseFetal Hemoglobin Can’t Bind 2,3 BPG and has Greater O2 Affinity Than Adult HemoglobinSickle Cell Anemia (SCA) is a Genetic Disease of HemoglobinIn Low O2 Concentration, Red Blood Cells of SCA Sufferers Form Sickle ShapesSickled Cells Stick in Capillaries and Can be FatalPeople Heterozygous for the Mutated Gene Survive Malaria Better Than Others
Protein Structure
Primary -‐ Sequence of amino acidSecondary -‐ Interaction of amino acids close in primary sequenceTertiary -‐ Interaction of amino acids distantly located
Protein Structure
Primary -‐ Sequence of amino acidSecondary -‐ Interaction of amino acids close in primary sequenceTertiary -‐ Interaction of amino acids distantly locatedQuaternary -‐ Interaction of protein subunits
Protein Structure
Metabolic Melody
Oh isn't it greatWhat proteins can do
Especially ones that bind to O2Hemoglobin's moving around
Inside of the lungs It picks up the bait
And changes itself from T to R state Hemoglobin's moving around
The proto-porphyrin system Its iron makes such a scene Arising when an O2 binds
Pulling up on histidine
The binding occurs Cooperatively
Thanks to changes qua-ter-nar-y Hemoglobin's moving around
It exits the lungs Engorged with O2
In search of a working body tissue Hemoglobin's moving around
Hemoglobin's Moving Around (To the tune of "Santa Claus is Coming to Town")
Copyright © Kevin Ahern
Oh isn't it greatWhat proteins can do
Especially ones that bind to O2Hemoglobin's moving around
Inside of the lungs It picks up the bait
And changes itself from T to R state Hemoglobin's moving around
The proto-porphyrin system Its iron makes such a scene Arising when an O2 binds
Pulling up on histidine
The binding occurs Cooperatively
Thanks to changes qua-ter-nar-y Hemoglobin's moving around
It exits the lungs Engorged with O2
In search of a working body tissue Hemoglobin's moving around
Hemoglobin's Moving Around (To the tune of "Santa Claus is Coming to Town")
Copyright © Kevin Ahern
The proton concentration Is high and has a role
Between the alpha betas It finds imidazole
To empty their loads The globins decree
"We need to bind 2,3BPG" Hemoglobin's moving around
The stage is thus setFor grabbing a few
Cellular dumps of CO2Hemoglobin's moving around
And then inside the lungs it Discovers ox-y-gen
And dumps the CO2 off To start all o'er again
So see how this works You better expect
To have to describe the Bohr effect Hemoglobin's moving around
Metabolic Melody
The Bloody Things(To the tune of “Coke ® It's The Real Thing”)
Copyright © Kevin Ahern
The Bloody Things(To the tune of “Coke ® It's The Real Thing”)
Copyright © Kevin Ahern
I’m gonna put some oxygensbeside my porphyrin rings
To nudge the irons up a notchand yank on histidines
The globins’ shapes will change a bit,oh what a sight to see
The way they bind to oxygenco-op-er-AH-tive-ly
And as I exit from the lungsto swim in the bloodstreamMetabolizing cells they allexpress their needs to meTo them I give up oxygenand change from R to T
While my amines, they hang ontothe protons readily
The Bloody Things(To the tune of “Coke ® It's The Real Thing”)
Copyright © Kevin Ahern
I’m gonna put some oxygensbeside my porphyrin rings
To nudge the irons up a notchand yank on histidines
The globins’ shapes will change a bit,oh what a sight to see
The way they bind to oxygenco-op-er-AH-tive-ly
And as I exit from the lungsto swim in the bloodstreamMetabolizing cells they allexpress their needs to meTo them I give up oxygenand change from R to T
While my amines, they hang ontothe protons readily
But that's not all the tricks I know,there's more that’s up my sleeve
Like gaps between sub-U-nits thathold 2,3-BPG
When near met-a-bo-LI-zing cells,I bind things that diffuse
The protons and bicarbonatesfrom lowly cee oh twos
CHORUS
That’s the way it isWhen your cells are at play
Go say hip hip hoorayFor the bloody things