erythrocyte membrane structure
Post on 31-Jan-2017
258 Views
Preview:
TRANSCRIPT
Eric NiederhofferMedical Biochemistry
What affects the normal functions of an erythrocyte?
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
Red Blood Cell: Biochemistry and Sickle Cell Disease
• RBC structuresize, spectrin, channels
• Metabolismglycolysis (2,3-BPG), pentose phosphate pathway (G6PDH, NADPH), glutathione
• Hemoglobingenes, heme, Mb/Hb (normal), HbS (defect), fibers (sickling and inflammation),
thalassemia
An Erythrocyte (RBC)
Reference RangesRBCs, male 4.3-5.9 x 106/µL female 3.5-5.5 x 106/µLHb, male 13.5-17.5 g/dL female 12.0-16.0 g/dLHct, male 41-53% female 36-46%MCV 80-100 fLMCH 25.4-34.6 pgMCHC 31-36 %RDW 11-14.5 %
Practical Values65% of Fe in Hb1 g Hb = 3.46 mg Fe1 mL blood at 15 g/dL Hb = 0.5 mg FeRBC x 3 = HbHb x 3 = HctMicrocytic < 80 fLMacrocytic > 100 fL
Erythrocyte Membrane Composition
http://www.ruf.rice.edu/~bioslabs/studies/sds-page/rbcmembrane.html
RBC Metabolic Pathways
2,3-BPG
BPG mutase
2,3-BPG phosphatase
PPP
NADPH
6PG
3-7 C metabolites(R5P, F6P, G3P)
G6PDHlactonase6PGDH
CO2
NADP+ + H+
GSH
GSSGGR
GP
H2O2 H2O
Glc
Pyr
G6P
1,3-BPG
3PG
HK
PGI
PK
F6P
G3P
PFK
aldolaseF16BP
DHAP
2PG
PEP
PGK
PGM
enolase
G3PDH
Glycolysis
LactateNo O2
LDH
Hemoglobin Genes and Gene Products
http://www.mun.ca/biology/desmid/brian/BIOL3530/DB_Ch09/fig9_24.jpg
Hemoglobin Gene Product Production
Mehta, A. B., and A. V. Hoffbrand. 2000. Haematology at a glance, Blackwell Science, Malden, Mass.
HbF: 2α and 2γHbA1: 2α and 2β
HbA2: 2α and 2δHbE: 2ζ and 2ε
Yolk sac Liver Spleen Bone marrow
Myoglobin and Hemoglobin Structure
deoxyHbdeoxyMb
oxyHb (HbO2)
O2
O2
O2
O2
Glu6→Val6
Glu6→Val6
oxyMb (MbO2)
O2
Hemoglobin Structure Changes
http://www.mfi.ku.dk/PPaulev/chapter8/images/8-3.jpg
Sickle Cell Disease
http://www.emedicine.com/ped/TOPIC2096.HTM
Rare combinations of HbS with HbD Los Angeles, HbO Arab, G-Philadelphia, among others
(>6 major genotypes)at least 1 sickle gene, hemoglobin S (HbS) ≥ 50% Hb present.
homozygotic HbSS (sickle cell anemia) - HbS = 100% Hb present
HbSbeta-0 thalassemia - Severe double heterozygote for HbS and beta-0 thalassemia; almost indistinguishable from sickle cell anemia phenotypically (MCV low)
HbSC disease - Double heterozygote for HbS and HbC, with intermediate clinical severity
HbS/hereditary persistence of fetal hemoglobin (S/HPHP) - Mild form or symptom free
HbS/HbE syndrome - Rare and generally mild clinical course
Hemoglobin Electrophoresis
http://themedicalbiochemistrypage.org/hemoglobin-myoglobin.html
Homozygous HbS
Normal neonate
Normal adult
HbSC
Heterozygous HbS
Relative protein charge
Start (samples applied here)
Anode (+)
Cathode (-)
Molecular Changes of HbS
http://www.sicklecellinfo.net/fiberformation.htm.Daniel J. Harrington, D. J., K. Adachi, and W. E. Royer, Jr. 1997. J. Mol. Biol. 272(3):398-407
Heme
Val
Molecular and Cellular Changes of HbS
http://www.emedicine.com/ped/TOPIC2096.HTM
Decreased PO2
Permanent damage to RBC
Cell endothelium interactions⟺
Effects of Therapy with Hydroxyurea
http://www.emedicine.com/ped/TOPIC2096.HTM
Thalassemiasα-thalassemia
β-thalassemia
HbH (β4)
Hb Barts (γ4)
Review Questions
• What proteins compose the membrane of erythrocytes?• What metabolic pathways are used in erythrocytes?• What is hemoglobin; what changes with sickle cell
disease?• What clinical observations would you make concerning
patients with SCD?• What are the thalassemias?
top related