Biochem (8/20/2010) Hemoglobin Protein Structure

Front 1

what is MCV?

Back 1

mean corpuscular volume

average volume of red blood cells

Front 2

what is leukopenia?

Back 2

decreased amount of white blood cells in the blood

Front 3

what is MCHC?

Back 3

mean corpuscular hemoglobin concentration

concentration of hemoglobin in a given volume of packed red blood cells

Front 4

what is thrombocytopenia?

Back 4

decreased clotting factors in the blood

Front 5

what is the primary function of myoglobin?

Back 5

store oxygen in muscle for release during periods of oxygen deprivation

monomeric protein with heme

Front 6

what is the primary function of hemoglobin?

Back 6

carry oxygen from lungs to tissues

tetrameric protein (2 alpha and 2 beta subunits) with heme

Front 7

to what does oxygen bind in hemoglobin?

Back 7

protoporphyrin IX

binding exhibits cooperativity between the four subunits

Front 8

what are the four primary regulators of oxygen binding to heme?

Back 8

carbon dioxide
2,3-BPG
proton
chloride

(all increase the proportion of T state monomers/decrease the affinity for oxygen)

Front 9

what is the T state of hemoglobin?

Back 9

tense state

the state of tetramers in hemoglobin molecules without oxygen bound, yielding reduced affinity for oxygen

Front 10

what is the R state of hemoglobin?

Back 10

relaxed state

the state of tetramers in hemoglobin molecules with oxygen bound, yielding increased affinity for oxygen

Front 11

what is HbA?

Back 11

normal adult form of hemoglobin

Front 12

what is HbF?

Back 12

normal fetal form of hemoglobin

Front 13

why does fetal hemoglobin have a higher affinity for oxygen than does adult hemoglobin?

Back 13

fetal hemoglobin has to steal the oxygen from the maternal hemoglobin at the placental barrier

Front 14

what is carbamino-Hb?

Back 14

hemoglobin in the T state with carbon dioxide non-covalently bound to the N-terminal residues

Front 15

when are protons released from hemoglobin?

Back 15

when oxygen binds, leading to T -> transition

when carbon dioxide binds, leading to hemoglobin carbamate

both demonstrating that conformation and oxygen binding to hemoglobin are sensitive to hydrogen ion concentration

Front 16

on what residues of hemoglobin do protons bind and release?

Back 16

histidine residues

Front 17

why do the liver and spleen enlarge during hemoglobinopathy?

Back 17

liver and spleen continue to try to produce the same amounts hemoglobin as in fetal life

Front 18

what are the qualitative hemoglobinopathies?

Back 18

sickle cell anemia (HbS)

change in the quality of hemoglobin made

Front 19

what are the quantitative hemoglobinopathies?

Back 19

thalassemias (alpha and beta)

change in the quantity of hemoglobin made

Front 20

what is the difference between sickle cell anemia and sickle cell trait?

Back 20

sickle cell trait - heterozygous single nucleotide polymorphism in beta hemoglobin gene (no symptoms except in oxygen deprivation conditions)

sickle cell anemia - homozygous single nucleotide polymorphism in beta hemoglobin gene (disease actually manifests)

Front 21

what is the difference between HbC and HbS?

Back 21

two different changes in the same codon (codon 6) of the beta chain of hemoglobin

Front 22

what causes the sickle shape of HbS cells?

Back 22

polymerization of deoxy HbS in the red blood cells

(reduces deformability also)

Front 23

why is HbF commonly found in patients with sickle cell anemia?

Back 23

to compensate for the functional problems of the HbS molecules

Front 24

what is the effect of hydroxyurea treatment for sickle cell anemia?

Back 24

in some patients, induces the expression of HbF to compensate for HbS, but not effective for all patients

Front 25

what are the symptoms of sickle cell anemia?

Back 25

moderately severe hemolytic anemia
hyperbilirubinemia leading to mild icterus and jaundice
reticulocytosis
vaso-occlusive crises
increased susceptibility to infection b/c of altered splenic function

Front 26

what is icterus?

Back 26

yellowing of sclera of eyes

Front 27

what is reticulocytosis?

Back 27

increased immature red cells in blood

Front 28

why does sickle cell anemia survive evolutionarily?

Back 28

advantage against malaria - heterozygotes are protected against malarial parasites

Front 29

alpha thalassemia

Back 29

called HbH disease

absence of 3 alpha-subunits leads to beta-tetramers

hemoglobin bart's precipitate in cells forming inclusion bodies

due to reduced oxygen-carrying capacity, heart failure in utero causes marked edema (hydrops fetalis)

Front 30

what is Hb Bart's?

Back 30

hemoglobin barts

tetramers of hemoglobin gamma subunits

Front 31

what is hydrops fetalis?

Back 31

a condition in the fetus characterized by an accumulation of fluid, or edema, in at least two fetal compartments

(can be caused by HbH)

Front 32

beta-thalassemia

Back 32

absence of beta hemoglobin subunits, leading to alpha hemoglobin tetramers

alpha tetramers are very unstable, destroying red blood cells in marrow and spleen

Front 33

what are the different types of beta thalassemia?

Back 33

beta0 - no beta subunits made

beta++ - less beta subunits than normal

Front 34

what is HbA1c?

Back 34

glycosylated adult hemoglobin

since red blood cells have a defined life cycle (120 days), can indicate how high and how long diabetics remain hyperglycemic

Front 35

what is the average fasting blood glucose?

Back 35

112 (5-6% HbA1c)