1. Hemoglobin & Myoglobin & Collagen

2. Heme proteins Supply of oxygen Myoglobin Oxidative metabolism
Monomeric
protein of red muscle
Stores oxygen

3. Hemoglobin
O2 transport
Tetrameric
Cooperative interactions

4. Normal Hemoglobins Hb A (α2β2) Hb F (α2γ2)
Major normal adult hemoglobin
Comprising about 97% of the total
Hb F (α2γ2)
Major hemoglobin of the fetus
Increased oxygen affinity
Lower affinity for 2,3-diphosphoglycerate (DPG)

5. Embryonic Hemoglobins
Hb A2 (α2δ2)
% of normal adult
Increased Hb A2
β-thalassemias
Embryonic Hemoglobins
Hb Gower-1 (ζ2ε2)
HbPortland (ζ2γ2)
Hb Gower-2 (α2ε2)

6. Developmental pattern of the quaternary
structure of fetal and newborn hemoglobins

7. Heme & ferrous iron
Fe2+ linked to all four nitrogen atoms of the heme, to histidine F8, and, in oxyMb & oxyHb, also to O2

8. Heme

9. Myoglobin O2 storage Rich in α Helix 153-aminoacyl residue MW 17,000
75% in eight right-handed
Helices A–H
Surface of myoglobin is polar
Interior contains only nonpolar
Leu, Val, Phe,

10. A model of myoglobin

11. Myoglobin Histidines F8 & E7
Roles in Oxygen binding
Proximal histidine, His F8
The fifth coordination position of the iron
O2 occupies the sixth coordination position

13. Hemoglobin Tetrameric the α polypeptide
α2β2 (HbA)
α2γ2 (HbF)
α2S2 (HbS)
α2δ2 (HbA2)
the α polypeptide
Seven helical regions
bind four molecules of O2 per tetramer

14. Cooperative binding
A molecule of O2 binds to a hemoglobin tetramer more readily if other O2 molecules are already bound

15. P50
expresses the relative affinities of different hemoglobins for oxygen
The partial pressure of O2 that half-saturates Hb
P50 for HbA and fetal HbF
26 and 20 mm Hg
HbF,High affinity for O2

16. On oxygenation of hemoglobin, the iron, histidine F8, and linked residues move toward the heme ring.

17. The iron atom moves into the plane of
the heme on oxygenation. Histidine F8 and its associated residues are pulled along with the iron atom.

18. rupture of salt bridges T (taut) state to the R (relaxed) state
Oxygenation of hemoglobin is accompanied by large conformational changes
binding of the first O2
Iron motion
rupture of salt bridges
T (taut) state to the R (relaxed) state
Low affinity and high-affinity conformations

20. The transition between the two structures is influenced by protons, carbon dioxide, chloride, and BPG; the higher their concentration, the more oxygen must be bound to trigger the transition.

21. After releasing O2 at the tissues, hemoglobin transports CO2 & protons to the lungs
CO2 as carbamates
15% of the CO2 in venous blood
Remaining

22. One proton for every two O2 molecules released
In the lungs, as O2 binds to deoxyhemoglobin, protons are released and combine with bicarbonate to form carbonic acid.

23. Bohr effect O2 Binds Reciprocal coupling of proton and O2 binding
Rupture of Salt Bonds
Proton release

24. The Bohr effect

25. Increase in proton concentration Increase in PO2
R state
Oxygenated
breaks salt bridges
Release of O2
the T structure
Salt bridges re-form
Increase in proton concentration
Enhances the release of O2
Increase in PO2
Promotes proton release

26. 2,3-Bisphosphoglycerate (BPG)
Stabilizes the T Structure of Hemoglobin
deoxyhemoglobin
Low PO2
Promotes the synthesis
Forming additional salt bridge

27. Mode of binding of 2,3-bisphosphoglycerate to human deoxyhemoglobin
Mode of binding of 2,3-bisphosphoglycerate to human deoxyhemoglobin. BPG interacts with three positively charged groups on each β chain.

28. Adaptation to High Altitude
Increase in
Number of erythrocytes
Concentrations of hemoglobin
BPG

29. Myoglobinuria Massive crush injury Myocardial infarction
Urine dark red
Myocardial infarction

30. Anemias Reductions in Number of red blood cells Hemoglobin
Folic acid or vitamin B12 deficiency
Hemoglobin
Iron deficiency

31. Glycosylated Hemoglobin (HbA1c)
ε-amino group of lysine residues
Amino terminals
Normal,about 5%
Proportionate to blood glucose concentration
Reflects the mean blood glucose concentration over the preceding 6–8 weeks
For management of diabetes mellitus

33. Numerous mutant human hemoglobins have been identified
Hemoglobinopathies & Thalassemias

44. Collagen a Fibrous Protein the most abundant of the fibrous proteins
25% of the protein mass in body
Strength & flexibility of skin
Collagen & keratin fibers
Bones & teeth
elongated proteins
repetitive amino acid sequences
regular secondary structure

45. Collagen
Primary, secondary, and tertiary structures of collagen

46. Collagen Rich in proline & hydroxyproline repetitive Gly-X-Y pattern
Y generally is proline or hydroxyproline

47. Collagen maturation Collagen Is Synthesized as a Larger Precursor
Procollagen
Prolyl hydroxylase
Lysyl hydroxylase

48. Collagen Collagen triple helices are stabilized by Hydrogen bonds
Residues in different polypeptide chains.
Hydroxyprolyl & hydroxylysyl
Covalent cross-links between
Modified lysyl residues both within and between polypeptide chains.

49. Hydroxylysyl residues
Glucosyl or galactosyl residues
Removal of the globular amino terminal & carboxyl terminal
Cross-link
Certain lysyl residues are modified
Lysyl oxidase
Copper-containing
ε-amino groups to aldehydes
aldol condensation
C=C double bond
C-N bond
Strength & rigidity

50. Order and location of processing of the fibrillar collagen precursor

51. Disorders of collagen maturation
Nutritional
Scurvy
Deficiency of vitamin C
Prolyl & lysyl hydroxylases
Bleeding gums, swelling joints, poor wound healing
Copper Deficiency
Lysyl oxidase

52. Disorders of collagen maturation
Genetic
Osteogenesis imperfecta
Fragile bones
Ehlers-Dahlos syndrome
Connective tissue disorders
Defects in the genes
α collagen-1
Procollagen N-peptidase
Lysyl hydroxylase
Mobile joints & skin abnormalities