Erythrocyte Biochemistry Flashcards
Human adults have _____ RBCs
We produce _____ RBCs per second
___% of hemoglobin is synthesized before the nucleus is extruded
The remaining ___% is made in the reticulocyte
25 trillion
2.4 million
65%
35%
Hemoglobin is a tetramer made of 2 _______ chains and 2 ________ chains
Hemoglobin contains 4 units of _______, which each contain a _______ iron atom, and they carry O2, heme is hydro______
Alpha-globin
Beta-globin
Heme
Ferrous (Fe2+)
Phobic
When there is a substitution of valine for glutamic acid at amino acid position #6 in B-globin, we see __________
Sickle cell anemia
Sickle cell anemia causes __________ of hemoglobin and ________ shaped RBCs which ____________ (also associated with __________ anemia)
Polymerization
Sickle-shaped
Impede circulation
Hemolytic
Hemoglobin in the muscle is called _________
It has a _______ affinity for O2 than Hemoglobin and has a _________ curve
Myoglobin
Higher
Hyperbolic
The steepest part of the dissociation curve of hemoglobin and oxygen affinity is from ______ pO2 with the low end corresponding to the onset of _________ and the high end corresponding to the onset of _______
20-40 torr
Exercise
Rest
The Oxygen dissociation curve of hemoglobin is shifted to the right by what factors?
Exercise, increased temperature, increased CO2, increased 2,3-BPG and decreased pH
What does positive cooperativity mean in regards to hemoglobin?
As one O2 binds to one heme, it facilitates the binding of O2 to another heme. Hb binds to O2 in a cooperative fashion.
When the ODC shifts to the right, Hb is giving up _______ to the _________
More O2
Tissues
Fetal Hemoglobin has a __________ affinity for O2 than the mother’s Hb because …
The fetal hemoglobin (HbF) curve is to the left or right of the normal Hb curve?
Higher
Because the baby needs to steal the mom’s O2 to get any
HbF is to the left
Iron readily exchanges _______and is the ideal catalyst for ______-________ reactions taking the dietary form of iron, ________ to a form usable in the blood, ____________.
Ions
Oxidation-reduction
Ferric 3+
Ferrous 2+
Because iron cannot freely diffuse across membranes, it involves several proteins. Name four.
Ferrireductase
DMT1 (divalent transporter)
Hephaestin
Ferroportin
Fe3+ is reduced to Fe2+ by ________
Dcytb. (Duodenal cytochrome b)
fe2+ is transported into the enterocyte by ________ on the apical surface
DMT1
Fe2+is transported outside the enterocyte cell into the blood by __________ with also requires _________ to perform the transport (changing Fe2+to Fe3+)
Ferroportin
Hephaestin (a ferroxidase)
_________ carries iron to tissues where it is needed, including the bone marrow undergoing erythropoiesis
It binds to iron with a _______ affinity and delivers iron safely in a ________ form.
Transferrin
High
Non-toxic
TfR stands for Transferrin Receptor and these mediate ___________
_________ have 800,0000 TfR per cell
In the cell, heme is made in the ___________
__________ is the protein that transports iron out of the endosome
Endocytosis
Erythroblasts
Mitochondria
DMT1
Organ disfunction due to iron overload is called ___________and may present as …
Treatment is _________
Hemochromatosis
Cirrhosis, arthritis, endocrinopathy, skin pigmentation, cardiomyopathy
(Usually manifest in 6th decade)
Treatment is blood-letting
A regulator of iron homeostasis that binds to ferroportin and causes internalization of ferroportin and its destruction by proteolysis is called ____________
This peptide is made by the ________
Hepcidin
Liver
When iron is high, hepcidin expression ________
And ferroportin levels ________
Increases
Decrease
When hepcidin decreases and ferroportin increases, iron must be _______ in the body
Low
HFE regulates _________ expression by binding to ________ which turns on ___________ expression
Hepcidin
TfR2
Hepcidin
If HFE is mutated, it cannot bind to _______ and there is no control over ________ because ________ wasn’t turned on
TfR2
Ferroportin activity
Hepcidin
The production of RBCs is dependent on which two vitamins?
Vitamin B12
&
Vitamin B9
Vitamin B12 is also known as _________
Vitamin B9 is also known as ________ or __________
Cobalamin
Folate or folic acid
Deficiency of vitamin B12 and folate causes ____________ anemia, which occurs as a result of diminished ___________ of __________ in the bone marrow erythroblasts
Megaloblastic
Synthesis
DNA
__________ anemias are characterized by large RBCs
What is another sign of this anemia on a slide
Macrocytic
Megaloblastic macrocytic anemia is seen as very large erythroblasts in the bone marrow as well as hypersegmented neutrophils (more than 5 lobes)
Folic acid, or pteroylglutamic acid, has 3 parts. Name them.
Pteridine
P-amino-benzocaine acid (PABA)
Chain of glutamate residues
Folate can exist as__________ which can be reduced to the active form of ________ by ___________
FH2
THF
Dihydrofolate reductase
The function of THF is to _________ ________ units (e.g. _______ groups) from doors to acceptors.
THF plays a vital role in _____ synthesis
Transfer
Carbon
CH3
DNA
THF becomes _____________ when the carbon side chain of serine is transferred to it, this is then transferred to ________to form ______ during which DHF is made and is then reduced by _________ to THF to restart the cycle
N5,10-methylene-THF
Deoxyuridylate (dUMP)
Deoxythymidylate (dTMP)
Dihydrofolate reductase
Folate is available as an N5-methyl-THF that needs to be ___________ in order to enter the folic acid cycle as THF. _________ is needed in order for this process to happen.
Demethylated
Cobalamin (B12)
If B12 is not available,the folate is stuck as ________
N5-methyl-THF
Cobalamin transfers the methyl group from N5-methyl-THF to ________ to create _________using the enzyme, ____________
Homocysteine
Methionine
Methionine synthase
Because a dietary deficiency of Vitamin B12 is rare, 85% of B12 deficiency is due to the lack of a protein called _______________
Intrinsic factor
In B12 absorption, dietary B12 binds to proteins called ________ made by gastric mucosa cells
R-binder proteins
Parietal cells of the stomach make ___________ and proteases from the pancreas degrade ________proteins in the duodenum, releasing ______
Then _________ carries B12 to the ileum where receptors bring it to the body
Intrinsic factor (44 kDa protein encoded by gene of Chr 11)
R-binder proteins
B12
Intrinsic factor
B12 receptor is _______
Cobalamin circulates through the blood carried by ___________
Cubulin
Transcobalamin
Pernicious anemia is a _____________ deficiency due to a lack of ____________ (which is necessary for absorption of the vitamin above)
This is a __________ __________ anemia
B12
Intrinsic factor
Megaloblastic macrocytic anemia
In order to determine whether a B12 deficiency is due to a failure of diet or absorption, the ___________ is used
Schilling Test
