Chpt 7 Flashcards
Blood Definition
Aqueous solution that functions as a transport and distribution system for the body
- Delivers nutrients, oxygen, minerals, metabolic products, and hormones
- Removes waste
Plasma
aqueous solution obtained following centrifugation of blood treated with anticoagulants
Anticoagulants
Ethylenediamine tetra acidic acid (E.D.T.A.)
-prevents coagulation by chelating divalent cations (Ca2+ and Mg2+)
Heparin
-prevent coagulation by binding to thrombin
Citrate
used when blood will be transfused
Serum
-aqueous solution obtained following centrifugation of coagulated blood (takes 30 to 45 mins)
Erythrocytes
RBCs
Function-Transport O2, CO2, Protons (H+) due to hemoglobin
Cellular remnant-lack nuclei and other organelles
- life span 60-120 days
- hemoglobin (and other proteins) synthesized prior to loss of organelles
Albumin
50% of protein in plasma
-polar; anion-20 negative charges at pH=7.4
Functions
1) protein reserve- synthesis 14-15 g daily, dependent on nutritional status; half life=20 days
2) osmotic regulator
3) Transport protein-divalent and trivalent cations (Cu2+ and Fe3+), hydrophobic molecules (fatty acids, sterols, bilirubin), Drugs (salicylates, barbiturates, sulfonamides, penicillin, and warfarin)
Metal Transport/Storage Proteins
1) Albumin
2) Transferrin
3) Ferritin
4) Hemosiderin
5) Ceruloplasmin
Transferrin (Metal Transport/Storage Proteins)
transports ferric iron (fe3+)
Ferritin (Metal Transport/Storage Proteins)
Iron Storage protein
-measured to determine iron deficiency ->since plasma ferritin is proportional to stored iron
Hemosiderin
- derivative of ferritin used to store iron
- liver, spleen, and bone marrow
- insoluble in aqueous solution forms aggregates
Ceruloplasmin
- transports copper (Cu2+)->liver to peripheral tissue
- regulates iron transport
- increase in ceruloplasmin concentration is observed in liver disease and tissue damage
Wilson’s Disease
Low ceruloplasmin-50 mmol/L (normal=200-450 mmol/L)
Elevated serum copper- 8mmol/L (normal=13-19 micromol/L
elevated excretion of Turin-2.2mmol/24 hrs (2-3.9 umol/24
Metabolic defect is in excretion of copper in bile and its reabsorption in the kidney
Myoglobin
- location
- function
- structure
Heme protein present in the heart and skeletal muscle
Functions:
- reservoir and oxygen carrier
- Binding of one oxygen/molecule of myoglobin is NON cooperative
Structure:
-150 amino acids
-8 alpha helixes (A-H)
-Amino acids with non polar R groups on Inside
-Amino acids with polar R groups on surface of molecule
Bound to Heme
Important OXYGEN information
Concentration of oxygen (or any gas in physiological solution) is usually express as partial pressure pO2.
-Barometric pressure=760mmHg=760 torr=101.3 kPascal (KPa)= 1 atm
Partial pressure of oxygen pO2
- Atmosphere= 150-160 mmHg
- Lungs and arterial blood= 100 mmHg
- Tissue (resting)=40 mmHg
- Tissue (exercising)= 20 mmHg
Heme Structure
Structure
1) Protoporphyrin IX and ferrous (Fe2+) iron
- iron (II) ferrous iron binds oxygen. (Iron (III) will not bind)
2) Iron forms 6 bonds
- 4 with N of photoporphyrin
- 1 with proximal histidine (F helix) of globin protein
- 1 with oxygen stabilized by distal histidine ( E helix)
3) Prosthetic group-nonprotein factor needed for enzyme activity
- covalently attached to enzyme (not dissociable)
** as oxygen binds, iron moved into the plane of hemoglobin
Heme Functions
1) bind/carries oxygen
- hemoglobin and myoglobin
2) carries electrons- redox rxns and cytochrome
3) breaksdown hydrogen peroxide-catalase
Hemoglobin A
Carries oxygen, carbon dioxide, and protons
Found exclusively in RBCs
Hemoglobin Structure
1) Heterotetramer
- 2 alpha chains
- 2 beta chains
- subunits attached by hydrophobic interactions
- each subunit binds one heme
T form (taut form)
- weak ionic and hydrogen bonds occur between AB dimer pairs in the deoxygenated form (T form)
- strong interactions-primarily hydrophobic between A and B monomers chains form stable AB dimers
R Form-oxygenated form
-some ionic and hydrogen bonds between AB dimers are broken in the oxygenated form
Hemoglobin: T form vs R form
T (tense or taut) Form= deoxygenated form
-low oxygen affinity
R (relaxed) form= oxygenated form
-high oxygen affinity
Cooperativity
Hemoglobin exhibits NOT MYOGLOBIN
Cooperativity
- as one oxygen binds, the affinity for another oxygen is increased
- Sigmodial dissociation curve
Dissociation curve: Myoglobin vs Hemoglobin
Myoglobin has a higher affinity for oxygen than hemoglobin
- Myoglobin binds one oxygen- hyperbolic curve
- Hemoglobin binds FOUR oxygens- Sigmoidal curve
Hemoglobins affinity for the fourth oxygen is 300x that of the first oxygen
steepest at the oxygen conc that occur in the tissues which allows oxygen delivery to respond to small changes in pO2
Allosteric Effects
Binding of Oxygen by hemoglobin is allosterically affected by:
1) pH (Bohr Effect)
- release of oxygen is enhanced by decrease in pH-> increase in [H+]
2) pCO2
- release of oxygen is enhanced by increase in [CO2]
3) 2,3-bisphosphoglycerate (2,3-BPG)
- synthesized from intermediate in glycolysis
- release of oxygen is enhanced by increase in [2,3-BPG]
- stabilizes taut form of hemoglobin
Bohr Effect
1) Increase in [H+]- decrease in pH
2) lowers the affinity of hemoglobin for oxygen
- pH (7.6) in alveoli of lungs is higher
- pH (7.2) in tissue is lower; production of organic acids (lactic acid) and Carbon dioxide (CO2)
Source of Protons
CO2+ H2O–> H2CO3
-carbonic anhydrase catalyzes the formation of carbonic acid from carbon dioxide and and water
H2CO3–> HCO3- + H+
-carbonic acid spontaneously dissociates into bicarbonate and a proton
as catabolism takes place, carbon dioxide is produced in the tissue
Carbon Dioxide effect on hemoglobin
- Most is transported as carbonic acid/bicarbonate
- some binds to hemoglobin as carbamate- CO2 binds to amino groups of hemoglobin-> carbamino-hemoglobin
- CO2 decrease the affinity of hemoglobin for oxygen
RIGHT SHIFT
2,3-bisphosphoglycerate effect on hemoglobin
1) Most abundant organic phosphate in RBC
2)increase in [2,3-BPG] enhances release of O2
-binds to packet formed by the two beta globin chains; contains positively charge amino acids
SHIFT RIGHT
Transfused blood
“Stripped of 2,3-BPG
- Prevented by adding inosine (hypoxanthineribose)
- enters hexose monophosphate pathway
Carbon Monoxide poisoning
CO binds tightly but reversibly to iron of hemoglobin-replaces Oxygen
Traps hemoglobin in relaxed form
- shifts saturation curve to hyperbola
- oxygen is NOT released into tissues
Fetal Hemoglobin (HbF)
HbF
1) has higher affinity for oxygen than HbA
- due to weak binding of 2,3-BPG by HbF
- faciltates transfer of oxygen across placenta from mother to fetus
Alpha Globin Gene Family
Chromosome 16
- Zeta- 2 copies
- alpha-16p13.3- 2 copies
Beta Globin Gene Family
Chromosome 11
- Epsilon
- Gamma types= A and G
- Delta
- Beta-11p15.4
types of hemoglobin protein
Embryonic Hemoglobin (HbE)-first 3 months of gestation
- Hb Grower I- two zeta and two epsilon subunits
- Hb Grower II-two alpha and to epsilon subunits
- Hb Portland I-two zeta and two gamma subunits
- Hb Portland II-two zeta and two beta subunits
Fetal Hemoglobin (HbF)
- final 6 months of gestation thru first few months after birth
- completely replaced by HbA by 6-12 months of age
- HbF- 2 alpha and 2 gamma subunits
Adult Hemoglobin (HbA) -FINISH
