Transcript heme synthesis

A 4-year-old African boy is brought in by his adoptive
parents who say that he has pain in his limbs and
does not want to walk
A 40-year-old man complains of progressive
exertional shortness of breath
How are CO2, NO, and O2 processed and transported?
How is heme synthesized?
Eric Niederhoffer
SIU-SOM
Small Molecule Processing
and Transport
• CO2 processing and transport
carbonic anhydrase, anion exchanger, carbamate formation, Bohr effect
• NO processing and transport
glutathione
• O2 processing and transport
hemoglobin/myoglobin structure, allostery, cooperativity
• Heme synthesis
pathway, disorders
CO2 Processing and Transport
CO2
from tissues
CO2
H2O
CA
HbNH2
H2CO3 + Hb(O2)4 + H+ + HbNH-CO2ClAE1 HCO 3
ClHCO3- +
H+Hb
+
O2
plasma
O2
to tissues
Percent Distribution of CO2
Species
Arterial Venous
Carbamino
5
30
HCO3CO2
dissolved
CO2
to air
CO2
H2O
CA
HbNH2
H2CO3 + Hb(O2)4 + H+ + HbNH-CO2AE1
ClHCO3plasma
ClHCO3- +
H+Hb
+
O2
O2
from air
87
8
60
10
NO Processing and Transport
http://www.comprehensivephysiology.com/WileyCDA/CompPhysArticle/refId-c090009.html
Hemoglobin Structure Changes
http://www.mfi.ku.dk/PPaulev/chapter8/images/8-3.jpg
Factors Affecting Binding of O2
Depends on pH ([H+]), CO2, BPG, Temp
Factors Affecting Binding of O2
Adaptation
Figures from
http://www.wiley.com/college/voet/047119350X/image_gallery
/ch10/index.html
Heme Synthesis
mit
SCoA + Gly
5-Aminolevulinic acid
synthase
Porphobilinogen
synthase
PBG
5ALA
Pb
PBG deaminase
Heme
Hydroxymethylbilane
Uroporphyrinogen
III synthase
UPGIII
Pb
Ferrochelatase
PPIX
UPGIII decarboxylase
Coproporphyrinogen oxidase
CPGIII
PPGIX
Protoporphyrinogen
oxidase
Review Questions
• How are CO2 and NO processed and transported?
• How are myoglobin and hemoglobin similar and
different?
• What portion of hemoglobin is involved in small
molecule transport?
• What allosteric effectors bind hemoglobin?
• How do allosteric effectors produce left and right
shifts of the hemoglobin-O2 binding curves?
• How is heme synthesized?
• How is heme synthesis regulated?