Biochem Flashcards
How is oxygen released from Hemoglobin (Hb) in the tissues?
Accumulation of waste products (CO2 and H+) will enter blood passing by tissue that needs oxygen and will displace the O2 from Hb.
How is oxygen binding to Hb favored in the lungs?
Once the blood reaches the lungs any H+ bound to Hb is released and bound to bicarb which is then converted to carbonic acid and CO2. The CO2 accumulates and is released into the alveoli. The high oxygen saturation in the alveoli and pulmonary capillaries also forces H+ and CO2 to be released from Hb.
Two components required for the synthesis of heme.
Glycine
Succinyl CoA
What should a physician suspect if a patient presents and PE notes bright red blood?
CO poisoning
How does O2 stabilize the Hb protein when it binds?
The heme portion of Hb is held in place by hydrophobic interactions with the rest of the globin proteins. It is only covalently linked at the F helix in position 8 (F8) using a histidine residue. Once O2 binds the Fe ion in heme, the entire complex can also form an ionic interaction with the histidine residue in the E helix at position 7 (E7) which stabilizes the whole 4 subunit protein.
The increased stabilization increases the affinity for more O2 to bind
Hb protein subunits in high concentration only in embryonic Hb.
Zeta subunits
Hb subunits only in high concentration in fetal Hb.
Gamma subunits
How does pH affect the oxygen saturation curve of Hb?
Low pH shifts the curve to the right indicating decreased affinity of Hb for O2.
How does an acidic pH stabilize the deoxy form of Hb?
H+ binds the N terminis of the Histidine residue at position 146 in the beta subunits giving the nitrogen a positive charge. This allows an ionic interaction with an Aspartate residue (with a negative charged C terminis) at position 94 in beta subunits. The interaction stabilizes the whole protein.
How does CO2 stabilize the deoxy form of Hb?
CO2 binds with terminal amino groups to form carbamate salt bridges between different ends of helices within the protein.
How does 2,3 bisphosphoglycerate (BPG) aid H+ and CO2 in releasing O2 from Hb to oxygenate tissues?
During hypoxic states the BPG protein is synthesized and acts in a similar mechanism to H+ by displacing the oxygen and stabilizing the deoxy state.
Why does fetal Hb have a higher affinity for O2?
Ensures that the fetus is able to get oxygen from the maternal blood. The mechanism is due to fetal Hb having a less affinity for BPG.
What affect does alpha and beta thalassemia have on Hb?
Alpha Thalassemia: means a defect in the alpha protein synthesis so the Hb has only beta subunits.
Beta Thalassemia: defect in beta protein synthesis so Hb has only alpha subunits.
Most common cause of alpha vs. beta thalassemia.
Alpha: deletion
Beta: point mutation
Why are alpha mutations worse in utero than in adults?
Alpha subunits are in both fetal Hb and adult Hb. It can impair fetal development in the Hb does not function properly. However in adults there are two genes (two from each parent so 4 total) that code the alpha subunits so a mutation in one gene is not that detrimental.
(Beta has only 1 gene, so mutations are more symptomatic in adults)
