Blood

• Oxygen physically diffused by

• 0.2ml / 100 ml blood

• By Hb 20ml / 100ml blood

• So it’s the main function .

(Eckert, Fig. 13-1)

Gas transfer system of vertebrates

Low PO2High PO2

High PCO2Low PCO2

Main functions of blood

• * transport :

• *Oxygen and carbon dioxide » - nutrients» Hormones» Metabolites » Force ( hydraulic )» Temperature

• Immunity

• Coagulation

Transport of O2 in the blood

Respiratory pigments After O2 diffuses across the respiratory

epithelium it is bound by a respiratory pigment

Respiratory pigments are complexes of proteins and metal ions

• 1. hemoglobin

• 2. chlorocruorin

• 3. hemerythrin

• 4. hemocyanin

• 5.myoglobin

Which in solution heavy, In cells lighter

Why Hb inside the cell

• VISCOSITY

• FIGURE 2,1

• CHEMISTRY O2 BINDING

Chlorocruorin

• Class Polychaeta

• contain Fe

• green in low oxygen, red when saturated

• In solution

Hemocyanin

• some , molluscs , crustaceans and arachnids

• blue when oxygenated and colorless when deoxygenated

• contain Cu• No porphyrin ring• In solution

Hemerythrin

• Present in the blood of certain marine invertebrates (e.g. sipunculoid worms, polychaetes)

• Contains iron but not a porphyrin ring • violet-pink when oxygenated, colorless when

deoxygenated• In cells

Hemoglobin (Hb)

Hemoglobin (Hb)• Increases the carrying capacity of blood for O2

• Four protein (globin) chains, each attached to an iron-containing heme group

• Each heme group consists of a porphyrin ring with an iron atom in the center

• In humans, there are forms of globin: , , in adults (2, 2)

• Form dimers 1 1 2 2

• each Subunits bonded to other by links ( hydrogen ,…)

• Fe bind to the 4 N with coordinate covalent bond

( the bond e pair is formally contributed by only of the atoms forming the bonds)

• The fifth is his residue from globin • The sixth is oxygen if exist • To give oxyhemoglobin • Each hb can carry 4 o• Subunit interactions altered when Hb binds to

O2 or to other molecules

(Silverthorn, Fig. 16-7)

• Hemoglobin loads up with oxygen in the lungs, forming oxyhemoglobin.

• As blood passes through the capillaries, some of the oxyhemoglobin releases oxygen and become deoxyhemoglobin.

Hemoglobin

- Carboxyhemoglobin: Hb saturated with CO

• Partially saturated hemoglobin – when one to three hemes are bound to oxygen

• The rate that hemoglobin binds and releases oxygen is regulated by:

– PO2, temperature, blood pH, PCO2, and the concentration of BPG (an organic chemical)

• These factors ensure adequate delivery of oxygen to tissue cells

Hemoglobin (Hb)

Hemoglobin

• Fetal hemoglobin:

• gamma chains (not β) w/ higher affinity for O

• (enhance O transfer from mother to fetus)

• Affinity for CO = 200 x’s greater than for O

• ( No, CO,H2S) poisoning even at low partial pressures

Oxidation of Fe yields 3+ charge - ferric iron

-methemyoglobin ( Met Hb) does NOT bind oxygen.

ON THE SIXTH PART AWATER MOLECULE

• Normally Fe may be oxidized ( few)

• So what :

• RBCs have a methemoglobin reductase , which convert small amount to – Hb normal.

Myoglobin

• Mb is a monomeric heme protein• a store oxygen protein facilitate diffusion • - found in skeletal & cardiac muscle• - contain one heme binds one O2• Globin:• - single polypeptide chain; 154• a.a.; 17.2 kD (monomer)• - 8 helicies (label A-H) 20

hemoglobin

141 =α

Β= 146

Myoglobin

• • Surface: polar; inside: non polar

• • Fe in Mb is Fe2+ - ferrous iron - the form that binds oxygen

• • Oxygen binds as the sixth ligand to Fe

• Higher affinity for O2 than Hb

Myoglobin

• Oxidation of Fe yields 3+ charge - ferric iron

-metmyoglobin ( MetMb) does NOT bind oxygen

• Cardiac muscle of diving mammals contain higher (8%) amounts of Myoglobin than most mammals (e.g. 0.5% for a dog)

Who's haven't: Antarctic Icefish body temperature:-1.7oC

Who's haven't

Antarctic ice fish lack pigment

• low metabolic needs = low metabolism

• high cardiac output, blood volume

• large heart

• O2 solubility 0.3%

• Blood has lower viscosity– Easier to pump

Vertebrate Hemoglobin

Polypetidechain

Hemegroups

(Fe center)

2X

2X

4 O2/Hb

How do respiratory pigments work?

• Reversibly Bind O2: heme group• Hb + O2 HbO2

• To work effectively Hb should:

1. Bind O2 at high PO2 (lung, eqn. shifts right)

2. Release O2 at low PO2 (working tissue, eqn. shifts left)

• Oxygen binding changes the Hb conformation

• – Without oxygen bound, Fe is out of heme plane

• – Oxygen binding pulls the Fe into the heme plane

• Fe pulls its His F8 ligand along with it

• The F helix moves when oxygen binds

• This change means little to Mb,

• but lots to Hb!

Mechanism of allosteric change

• Heme iron move <= 0.04 nm induces

• conformation change in Hb

• • One alpha-beta pair moves relative to the other

by 15 degrees upon oxygen binding

• • This massive change is induced by movement of Fe by 0.039 nm when oxygen binds

• Oxy and deoxy form represent 2 different

• conformation states

• - Hb binds O2 (from T R)

Cooperativity• Binding 1 O2 “loosens” conformation of Hb

subunits– when “loose”, small changes in PO2 can result in

large changes in saturation

“tight”

“relaxed”

O2

• Cooperative oxygen binding and release is evident in the dissociation curve for hemoglobin.

• Where the dissociation curve has a steep slope, even a slight change in PO2 causes hemoglobin to load or unload a substantial amount of O2.

• This steep part corresponds to the range of partial pressures found in body tissues.

• Hemoglobin can release an O2 reserve to tissues with high metabolism.

• Hemoglobin saturation plotted against PO2 produces a oxygen-hemoglobin dissociation curve

• 98% saturated arterial blood contains 20 ml oxygen per 100 ml blood (20 vol %)

• As arterial blood flows through capillaries, 5 ml oxygen are released

Influence of PO2 on Hemoglobin Saturation

Hb-O2 Dissociation Curve

Desaturated

“tight”

Cooperativity“loose”

Saturation

PO2

PO2

Fig 42.28

Hb + O2 <--------> HbO2

Fig 42.27

1 1

2

2 (resting tissue)

3 (exercising musc.)

• Hemoglobin is almost completely saturated at a PO2 of 70 mm Hg

• Further increases in PO2 produce only small increases in oxygen binding

• Oxygen loading and delivery to tissue is adequate when PO2 is below normal levels

Hemoglobin Saturation Curve

• Only 20–25% of bound oxygen is unloaded during one systemic circulation

• If oxygen levels in tissues drop:– More oxygen dissociates from hemoglobin

and is used by cells – Respiratory rate or cardiac output need not

increase

Hemoglobin Saturation Curve

Figure 22.7 Respiratory pigments display hyperbolic or sigmoid oxygen equilibrium curves (Part 1)

Details of Mb-O2 binding

site

Proximal Histidine: coordinated to heme iron