IHL I - Hemoglobin Synthesis and Metabolism

Question 0

structure of heme

Answer 0

porphyrin ring with one iron chelated in the center by 4 nitrogens

iron has 6 binding sites

- 4 nitrogen
- 1 to protein structure
- 1 to oxygen

Question 1

two major components of hemoglobin

Answer 1

heme and blogin

heme 3%

Question 2

how many hemes per hemoglobin?

Answer 2

4 hemes (4 irons) each can carry 4 oxygen

16 O2 molecules per hemoglobin

Question 3

porphobilinogen

Answer 3

first step in heme synthesis

-succinyl CoA and glycine decarboxylation eventually give porphobilinigen

Question 4

delta-aminolevulinate synthase (ALA synthase)

Answer 4

committed step of heme synthesis
catalyzed reaction:
glycine and succinyl CoA > delta-aminolevulinic acid

(-) Heme - represses transcription of the enzyme

Question 5

PBG Synthase (porphobilinogen synthase)

Answer 5

aka ALA dehydratase

catalyzes reaction:
2x delta-aminolevulinic acid > porphobilniogen

occurs in the mitochondria

Question 6

protoporphyrin

Answer 6

condensation of four porphobilinogen > protoporphyrin

forms in the cytosol

iron is inserted into protoporphyrin by ferrochelatase

Question 7

ferrochelotase

Answer 7

inserts the iron into the protoporphyrin ring

occurs in the mitochondria

Question 8

sideroblastic anemia

Answer 8

due to mutation in the delta-aminolevulinic acid synthase (ALA synthase)

Question 9

porphyria

Answer 9

due to mutations in ALA dehydratase or PBG deaminase

- results in accumulation of these in the skin
- very photosensitive
- red-colored urine

Question 10

lead poisoning

Answer 10

inhibits ALA dehydratase and ferrochelatase

accumulation of molecules

- causes basophilic stiffling
	- little purple dots in the RBCs

Question 11

globin synthesis

Answer 11

in the cytoplasm of immature RBCs

somehow there is a balance of heme and globin
-unknown mechanism

Question 12

chromosome 16

Answer 12

alpha chains of globin

Question 13

chromosome 11

Answer 13

beta globin chains, as well as delta and gamma

Question 14

thalassemia

Answer 14

disruption of balance in the globin and heme synthesis

Question 15

hemoglobin synthesis

Answer 15

combination of heme and globin in the immature RBCs in bone marrow

Question 16

transferrin

Answer 16

transports iron in the body

Question 17

location on heme synthesis

Answer 17

mitochondria

Question 18

location of globin synthesis

Answer 18

cytoplasm ribosomes

Question 19

Hb A

Answer 19

normal adult hemoglobin

2 alpha and 2 beta chains

Question 20

variation in hemoglobin?

Answer 20

heme all the same

globin chains can be different

Question 21

Hb F

Answer 21

2 alpha and 2 gamma

fetal hemoglobin

Question 22

Hb A2

Answer 22

2 alpha and 2 delta

Question 23

hemoglobin through development?

Answer 23

conception to 3 months
	-have Gower hemoglobin (e and zeta)
		-not in adult
at 3 months until birth
	-Hb F forms (gamma chain production)
		-doesn't let oxygen go easily
at birth - beta chain is synthesized
	-Hb A1 (normal adult hemoglobin) > around 6 months
increased in delta chain is slight throughout life
	-increases Hb A2

Question 24

deoxyhemoglobin

Answer 24

without oxygen

Question 25

oxyhemoglobin

Answer 25

hemoglobin carrying oxygen

Question 26

pulse oximetry

Answer 26

infrared light measures absorption of deoxy and oxyhemoglobin -can compute the oxygen saturation levels

Question 27

methemoglobin

Answer 27

when Fe2+ oxidized to Fe3+ -due to oxidizing drugs > nitrites, sulfonamides cannot carry O2

Question 28

methemoglobin reductase

Answer 28

converts methemoglobin to hemoglobin

Question 29

sulfhemoglobin

Answer 29

partially denatured hemoglobin - RBC desctruction and hemolysis - cannot carry O2 due to sulfur drugs and aromatic amine drugs

Question 30

carboxyhemoglobin

Answer 30

hemoglobin carrying carbon monoxide elevated in individuals with carbon monoxide poisoning

Question 31

ferrous

Answer 31

Fe2+ binds oxygen

Question 32

ferric

Answer 32

Fe3+ cannot carry O2

Question 33

major sources of iron in the body?

Answer 33

heme and nonheme

Question 34

nonheme

Answer 34

can be either ferric or ferrous ferrous absorbed more readily -reduced at the membrane by ferric reductase

Question 35

ferric reductase

Answer 35

reduces iron at the membrane so it can be transported

Question 36

DMT-I

Answer 36

cotransporter of Iron and H+ ions into the enterocyte

Question 37

mobilferrin

Answer 37

binds to the free iron in the enterocyte and transport to basolateral membrane

Question 38

hemochromatosis

Answer 38

too much iron given phlebotomys and chelating agents (to bind iron)

Question 39

iron storage locations?

Answer 39

spleen, liver, duodenum spleen - old RBCs broken down

Question 40

apoferritin

Answer 40

part of the iron buffer system ferritin is the storage form of iron

Question 41

RBC destruction

Answer 41

circulate for 120 days > then become senescent RBCs

Question 42

erythrocyte energy production?

Answer 42

glycolysis and pentose phosphate 90% glucose in glycolysis

Question 43

glycolysis in erythrocytes

Answer 43

formation of ATP which mantains the membrane ion pumps (ATP) and reoxidation of hemoglobin (NADH)

Question 44

pentose phosphate pathway in erythrocytes

Answer 44

provides NADPH to maintain the reduced state of glutathione and sulfhydryl groups

Question 45

spleen

Answer 45

"red cell graveyard" red blood cells lose size and become rigid as they age

Question 46

polycythemia

Answer 46

rate of RBC synthesis > degradation

Question 47

anemia

Answer 47

RBC destruction > synthesis

Question 48

hemoglobinemia

Answer 48

intravascular hemolysis of RBCs due to conditions such as hemolytic anemia, autoimmune processes, transfusion reactions, and drug-induced hemolysis > free Hg in plasma

Question 49

hemoglobinuria

Answer 49

increased Hg in the urine excess Hg is nephrotoxic in kidneys***

Question 50

three components of Hg breakdown

Answer 50

Fe, protoporphyrin, and globin broken down heme oxygenase -forms CO and biliverdin biliverdin reduced to bilirubin

Question 51

Hemoglobin S

Answer 51

sickle cell anemia beta chain position 6 glutamic acid changed to valine*** missense mutation > results in Hg S synthesis

Question 52

Sickle Cell Anemia

Answer 52

hemoglobin is susceptible to polymerization - causes sickling - results in inflexibility and hemolysis

Question 53

Thalassemias

Answer 53

quantitative defect -imbalance in heme to globin ration due to mutations in globin chain synthesis

Question 54

microcytic hypochromic anemia

Answer 54

small in size and decrease in color

Question 55

alpha thalassemia

Answer 55

decreased alpha globin synthesis | -results in excess of beta and gamma chains

Question 56

hemoglobin H disease

Answer 56

loss of 3 out of 4 alpha globin genes in adult | -results in Hg H (hemoglobin tetramers)

Question 57

thalassemia major

Answer 57

loss of all 4 alpha chain globin results in formation of Hemoglobin barts (gamma tetramers) -can cause hydrops fetalis

Question 58

hydrops fetalis

Answer 58

incompatible with life -hepatosplenomegaly caused by loss of all 4 alpha globin chains

Question 59

beta-thalassemia

Answer 59

excess of alpha globin chains elevated Hg F and Hg A2 different ranges: minor > major

Question 60

beta-thalassemia minor

Answer 60

heterozygous | -asymptomatic, may require genetic counseling

Question 61

beta-thalassemia major

Answer 61

homozygous disorder significant imbalance of alpha and beta chains -sever anemia in early life requires life-long RBC transfusion untreated, death in first decade aka cooley's anemia