Hemoglobin Flashcards
What does hemoglobin do?
Transports O2 from the lungs to tissue
Facilitates CO2 transfer from tissue to lungs
What is hemoglobin?
A highly specialized intracellular RBC protein
Hemoglobin occupies how much of the volume of RBC?
33%
How much does hemoglobin account for RBC dry weight?
90%
Each cell contains how how much hemoglobin?
28 - 34 pg
Most hemoglobin synthesis occurs in what?
Polychromatophilic normoblast
What percentage of hemoglobin is made before the nucleus is extruded?
75 - 80%
20 - 25% of hemoglobin was made by what?
Residual RNA & mitochondria in the reticulocyte
Hemoglobin concentration is the result of a fine balance between what?
RBC production & destruction
Hemoglobin has what type of protein?
Globular protein 64.4 kD
How many hemoglobin are there per RBC?
250 million / RBC
What are the components of the molecular hemoglobin structure?
2 alpha chains 2 beta chains Each chain has a heme Each heme has a tetrapyrrole ring with iron (Fe2+) in the center Each iron/heme can bind to one O
What are the functions of hemoglobin?
Transport & release oxygen to tissues with specific conditions
Removal of CO2
What are the two conformations of hemoglobin?
“Relaxed”Oxyhemoglobin
“Tense”Deoxyhemoglobin
What does relaxed oxyhemoglobin have?
High affinity for O2
What does tense deoxyhemoglobin have?
Low affinity for O2
2,3-DPG (diphosphoglycerate)
When hemoglobin has a high affinity for O2 what happens?
It binds to O2 more avidly
Does not readily release it
When hemoglobin has a low affinity for O2 what happens?
Releases its O2 more readily to tissues
What does respiratory movement mean in regards to hemoglobin?
It has an allosteric shape with oxygen addition & release
How does 2,3-DPG affect oxygen affinity?
It’s the primary allosteric regulator of Hb
Large amounts of 2,3-DPG changes Hb from relaxed to tense
Increased 2,3-DPG shifts O2 saturation cure to what direction?
Right
What type of protein is hemoglobin?
Allosteric protein
Allosteric protein means that it does what?
Changes shape
What molecules affect Hb?
Protins (H+)
CO2
2,3-DPG
What preferentially binds to deoxyhemoglobin?
2,3-DPG,
CO2
H+
When 2,3-DPG , CO2, or H+ bind to deoxyhemoglobin what happens?
Forms salt bridges within & between chains
Stabilizes T conformation of Hb
2,3-DPG binds to Hb in what ratio?
1:1
Where does 2,3-DPG bind to on hemoglobin?
In the central cavity of the Hb tetramer between the beta-globin chains
When 2,3-DPG binds to Hb what happens?
Stabilizes the quarternary structure of deoxyhemoglobin
What type of interaction is O2 binding to Hb?
Heme-heme interaction
What is the ratio that O2 binds to H2?
4:1
One O2 binds to each heme group of the tetramer
Does the T conformation of deoxyhemoglobin have low or high O2 affinity?
Low
When O2 is loaded onto the Hb molecule what happens?
Salt bridges are broken causing the molecule to go from tense to relaxed state when the third O2 is loaded
Pulls the beta-chains together & expels 2,3-DPG
When O2 is released by Hb into the tissues what happens?
Heme pockets narrow
Restrict entry of O2
Space between the beta-chains widen
2,3-DPG binds again in the central cavity
Tense hemoglobin is called what?
Deoxyhemoglobin
O2 affinity is usually expressed as what?
PO2 at which 50% of the Hb is saturated with O2 (P50)
P50 in humans ˜26-28 torr (mmHg)
Bohr effect
Physiological phenomenon stating that hemoglobin’s oxygen binding affinity is inversely related both to acidity & the concentration of carbon dioxide
Increase of CO2 decreases pH -> Hb releases O2
Decrease of CO2 increases pH -> Hb picks up O2
Increased acid shifts the oxygen dissociation curve which way?
Right
Decreased acid shifts oxygen dissociation curve which way?
Left
What values (high/low) of pH, DPG, temp, & P50 for a right shifted oxygen curve?
Low pH
High DPG
High temp
High P50
What is P50?
50% of Hb is saturated with O2
What values (high/low) of Hb, pH, DPG, temp, & P50 are a left shifted oxygen curve?
High Hb High pH Low DPG Low temp Low P50
What are the types of abnormal hemoglobin?
Carboxyhemoglobin
Methemoglobin
Sulfhemoglobin
Carboxyhemoglobin is formed when?
Hb is exposed to CO (carbon monoxide)
Carboxyhemoglobin results in a shift in what direction?
Left
Carboxyhemoglobin results in high/low affinity & a high/ low release of O2 by what?
High affinity
Low release of O2
Remaining normal to Hb molecules
What color is the blood & skin due to carboxyhemoglobin?
Cherry red
What causes methemoglobin?
Hb with iron in the ferric (Fe+++) state
Hb affinity for CO is 200 times higher than for O2 is?
Carboxyhemoglobin
In methemoglobin Hb can or cannot bind O2?
Cannot
In methemoglobin Hb has a high/low affinity of remaining normal Hb & increases/decreases O2 carrying capacity of the blood?
High afffinity
Decreases O2 carrying capacity
Methemoglobin can be what three types?
Congenital
Hereditary
Acquired
The blood sample can be what in color?
Chocolate brown
Sulfhemoglobin is caused when?
A sulfur atom binds to periphery of porphyrin ring of the heme group of Hb
Characteristics of sulfhemoglobin are?
Stable compound
RBC carries it until the cell is removed from circulation
Can combine with CO to form carboxysulfhemoglobin
Sulfhemoglobin is elevated in what conditions?
Severe constipation
Bacteremia with Clostridium
Sulfhemoglobin is associated with what?
Occupational exposure to sulfur compounds
Environmental exposure to polluted air
Exposure to certain drugs
May build up with chronic constipation & is irreversible?
Sulfhemoglobin
Patient blood has chocolate brown color?
Methemoglobin
200 times the affinity for hemoglobin than oxygen, easily fatal?
Carboxyhemoglobin
What will NOT shift the oxygen dissociation to the right?
Increased pH
What are the steps in hemoglobin composition synthesis?
4 globin chains - protein synthesis
Each globin has 1 heme - heme synthesis
Each heme has 1 iron - iron transport/storage
What is heme?
An iron containing non-protein portion of the hemoglobin molecule
What is the structure of heme?
Ferro-protoporphyrin, a cyclical compound with 4 Pyrrhole rings* held together by nitrogen bonds holding an atom of iron in the center
Each heme contains one atom of what?
Ferrous iron
Ferrous iron has a bond that does what?
Reversibly binds oxygen
Hemoglobin biosynthesis occurs where?
Mitochondria
What is COPRO?
Coproporphyringen
What is PROTO?
Protoporhpyrin
What is the sequence of heme biosynthesis (6 parts)?
ALA PBG - Porphobilinogen URO - Uroporphyrinogen COPRO - Coproporphyrinogen Protoporphyrinogen/PROTO - Protoporphyrin IX
Assembly of hemoglobin occurs where?
Mitochondria
What hemoglobins are in adults?
HbA - a2b2
Alpha 2 Beta 2
What hemoglobin are in newborns?
a2g2 Fetus - HbF
Alpha 2 Gamma 2
What hemoglobins are found in small amounts in adults?
a2d2 - HbA2
Alpha 2 Delta 2
What hemoglobins are found in embryos?
a2e2
Alpha 2 Epsilon 2
Adult hemoglobin consists of 2 alpha and 2 ____ globins?
Beta
Fetal hemoglobin consists of 2 alpha and 2 _____ globins?
Gamma
What hemoglobin starts in the fetus?
Beta
What hemoglobin is in the fetus?
Gamma
What is the sequence of hemoglobin from embryo to birth?
Epsilon Gamma Beta
What type of hemoglobin is in the embryonic stage?
Epsilon
What hemoglobin is in the fetal stage?
Gamma
What hemoglobin is present throughout a persons life?
Alpha
What hemoglobin starts high before birth but drops after birth?
Gamma
What hemoglobin starts low before birth but then goes up after birth?
Beta
What is the correct order of heme synthesis?
Succinyl CoA + glycine Delta ALA Porphobilinogen Uroporphyrinogen Coprophorphyrinogen Protophorphyrinogen Heme
Tense hemoglobin has what?
2,3-DPG
A patient with pH of 7.035 will have what effect on hemoglobin saturation?
Shift to the right
What globin chain is turned on during embryonic development and stays on?
Alpha
