MyoglobinandHemoglobin

AtifH.Khirelsied,Ph.D. Atif H. Khirelsied, Ph.D.

DepartmentofBiochemistry

FacultyofMedicine
InternationalUniversityofAfrica,Khartoum,Sudan

Myoglobin andHaemoglobin
M l bi Myoglobinandhemoglobinarehemeproteins. dh l bi h i Theyareprincipallyinvolvedinbindingmolecular oxygen.

Myoglobin
Isamonomerichemoprotein. Anintracellularstorageforoxygeninmuscletissue. Releasesitsboundoxygenduringperiodsofoxygen deprivation. d i i

Myoglobin structure
Thetertiarystructureofmyoglobinisatypicalglobular protein. protein It h Ithasaveryhighproportion(75%)ofhelix. hi h ti (75%) f h li Comprises8helices,designatedAtoH,connectedby i 8 h li d i d db shortnonhelicalregions.

Myoglobin peptide

Myoglobin structure
Aminoacidpackedintotheinteriorofthemoleculeare predominantlyhydrophobic whilethoseonthesurface arehydrophilic. h d hili

Eachmyoglobinmoleculecontainsonehemeprosthetic groupinsertedintoahydrophobiccleftintheprotein.

Myoglobin structure
Eachhemeresiduecontainsonecentralcoordinately boundironatomintheFe2+ (ferrous)state.

Th Theoxygenisbounddirectlytotheferrousironatom. i b d di tl t th f i t

OxidationoftheirontotheFe3+(ferric)staterendersthe moleculeincapableofnormaloxygenbinding.

Myoglobin structure
Hydrophobicinteractionsbetweenthetetrapyrrolering andhydrophobicaminoacidontheinteriorofthecleft stronglystabilizethehemeproteinconjugate. t l t bili th h t i j t

AnitrogenatomfromahistidineR grouplocatedabove theplaneofthehemeringiscoordinatedwiththeiron atomprovidesfurtherstabilization. f

Porphyrin ring

Heme

Myoglobin
Inoxymyoglobin the6thcoordinatepositionisoccupied bytheoxygen,whosebindingisstabilizedbyasecond histidineresidue. histidine residue.

CObindscoordinatelytohemeironinamannersimilar tothatofoxygen,butismuchstronger.

Haemoglobin
Hemoglobinisatetrameric hemeproteinfoundinRBCs g p Each subunit of a hemoglobin has a heme prosthetic Eachsubunitofahemoglobinhasahemeprosthetic group. Thepeptidesaredesignated,,,and whichare arrangedintovariousformsoffunctionalhemoglobins. g g

Developmentalpatternofthequaternarystructureoffetal andnewbornhemoglobins g

Haemoglobin
ThesecondaryandtertiarystructureofHb.subunits aresimilar,withextensivehomologyinaminoacid composition.

ThequaternarystructureofHb.yieldstophysiologically importantallostericinteractionsbetweenthesubunits,

Myoglobin

Th ThecurveofoxygenbindingtoHbissigmoidal f bi di t Hb i i id l typicalofallosteric. When oxygen binds to the first subunit of Whenoxygenbindstothefirstsubunitof deoxyhemoglobinitincreasestheaffinityofthe remainingsubunitsforoxygen. remaining subunits for oxygen

ThecurvesofoxygenbindingtoHb andMb

TheeffectofoxygenbindingtoHb.
Binding of oxygen to iron of deoxyHb pulls the iron BindingofoxygentoironofdeoxyHbpullstheiron atomintotheplaneoftheheme. SincetheironisalsoboundtohistidineF8,this residueisalsopulledtowardtheplaneoftheheme ring. i The resulting conformational change is transmitted Theresultingconformationalchangeistransmitted throughoutthepeptidebackbonecausingasignificant changeintertiarystructureofHb. g y

TheeffectofoxygenbindingtoHb.
The conformation of the low affinity, deoxygenated Theconformationofthelowaffinity,deoxygenated hemoglobin(Hb)isknownasthetaut(T)state. Theconformationofthefullyoxygenatedhighaffinity formofhemoglobinisknownastherelaxed(R)state. form of hemoglobin is known as the relaxed (R) state

TheconformationalchangesduringoxygenbindingtoHb.

Deoxygenated D t d

Oxygenated

The regulation of oxygen binding to Hb

InthecontextoftheaffinityofHb foroxygenthereare fourprimaryregulators,eachofwhichhasanegative p y g , g effect.Theseare o CO2, o hydrogen ion (H+), hydrogenion(H ), o chlorideion(Cl), o 2,3bisphosphoglycerate.

TheregulationofoxygenbindingtoHb
InthehighpO2 ofthelungsthereissufficientO2 to g p g overcometheinhibitorynatureoftheTstate. TheO2 bindinginducesalterationfromtheTformto theRform.

TheregulationofoxygenbindingtoHb

Whenoxyhemoglobinreachesthetissuesthe pO2issufficientlylow,aswellasthepH( 7.2), pO2 is sufficiently low as well as the pH (~7 2) thattheTstateisfavoredandtheO2 released. 4O2 +Hb<>nH++Hb(O2)4

TheregulationofoxygenbindingtoHb
Inthetissues,CO2,H+andCl exerttheirnegativeeffects onHbbindingofO2 MetabolizingcellsproduceCO2 whichdiffusesintothe bloodandentersthecirculatingRBCs. WithinRBCstheCO2israpidlyconvertedtocarbonic acidthroughtheactionofcarbonicanhydrase.

TheregulationofoxygenbindingtoHb
TheHCO3 ionproducedinthisdissociationreactiondiffuses outoftheRBCandiscarriedinthebloodtothelungs. t f th RBC d i i d i th bl d t th l This effective CO2 transport process is referred to as ThiseffectiveCO transportprocessisreferredtoas isohydric transport. Approximately80%oftheCO2 producedinmetabolizingcells istransportedtothelungsinthisway. AsmallpercentageofCO2istransportedinthebloodasa dissolvedgas. dissolved gas

Theroleof2,3bisphosphoglycerate
2,3bisphosphoglycerate derivedfromtheglycolysis. It is a potent allosteric effector on the oxygen binding Itisapotentallostericeffectorontheoxygenbinding propertiesofHb. 2,3BPGbindstoacavityinthecenterofthe deoxygenatedTformofHb. d t dTf f Hb

Theroleof2,3bisphosphoglycerate
Increased2,3BPGconcentrationfavorsconversion , ofRformHbtoTformHbanddecreasesthe amountofoxygenboundbyHbatanyoxygen concentration. concentration

HBFbindingaffinity
Hb molecules differing in subunit composition have Hb.moleculesdifferinginsubunitcompositionhave different2,3BPGbindingproperties. Forexample,HbF binds2,3BPGmuchlessavidlythan HbA. HbFinfetusesbindsoxygenwithgreateraffinity than themothersHbA. the mothers HbA

HBalsotransposrts CO2 andprotonstolungs

HemoglobincarriesCO2 ascarbamatesformedwith theaminoterminalnitrogensofthepolypeptide chains.