Heme Synthesis & Hemoglobin Flashcards Preview

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Flashcards in Heme Synthesis & Hemoglobin Deck (49):
1

What are the 3 main functions of heme?

transport of O2
electron transport
oxidation-reduction reactions (cyps)

2

Where is heme produced?

bone marrow-hemoglobin
liver-cyps
all other cells EXCEPT mature erythrocytes

3

What is a porphyrin?

cyclic tetrapyrroles capable of chelating to various metals to form essential prosthetitic groups for various biological molecules

4

What is heme?

Ferroprotoporphyrin IX

5

Does heme contain Fe3+ or Fe2+?

Fe2+

6

Where is ALAS localized to?

inner mitochondiral membrane

7

What is ALAS dependent on as a cofactor?

PLP (pyridoxal phosphate)

8

What are the 2 isoforms of ALAS? Location?

1-liver
2-erythroid/reticulocyte

9

Which isoform of ALAS undergoes feedback inhibition?

ALAS1-feedback inhibition by heme (at translational and transcriptional levels & mitochondrial import)
ALAS2-NOT regulated by feedback inhibition

10

How can lead poisoning affect the ALAD reaction?

Pb2+ can displace Zn2+ and eliminate catalytic activity, this leads to increased ALA in urine

11

What does lead poisoning mimic?

Acute porphyrias

12

What affects does ALA have on the brain?

it is toxic, causes the neurological effects of lead poisoning, Pb2+ may also directly affect nervous system

13

What does UROS do?

step 3 pt 2
converts uroporphyinogen III to the right isomer

14

What does ALAS do?

step 1
condenses glycine and succinyl Co-A to yield ALA

15

What does ALAD do?

step 2
condenses 2 molecules of ALA to form one molecule of PBG

16

What does PBGD do?

step 3 pt 1
form a linear tetrapyrrole

17

What does UROD do?

step 4
decarboxylates acetate side chains to methyl group

18

What does CPO do?

step 5
converts propionic acid side chains to vinyl groups

19

What does PPO do?

step 6
converts rpotoporphyrinogen IX to protoporphyrin IX

20

What does ferrochelatase do?

enhance the rate of Fe2+ into protoporphyrin IX insertion

21

What can inhibit ferrochelatase?

lead (increase protoporphyrin in urine)
iron deficiency

22

What is porphyria?

defect in heme biosynthesis
inherited or acquired

23

Inheritance of porphyria?

Al are AD except congential erythropoietic prophyria (AR)

24

What is the most common porphyria?

Porphyria cutanea tarda (PCT)

25

Most common acute porphyria?

Acute Intermittant Porphyria (AIP)

26

Most common erythropoietic porphyria?

Erythropoietic protoporphyria (EEP)
most common porphyria in childhood

27

What are symptoms of porphyrias with early defects?

accumulation of ALA, neurologic dysfunction

28

What are symptoms of porphyras with late defects?

sunlight induced cutaneous lesions, due to accumulation of cyclic tetrapyrroles, generare ROS

29

Acute porphyria symptoms? causes?

periodic acute attacks
abdominal pain, neuro defects, psych, red urine
casuses: drugs, environment, diet

30

chronic porphyria symptoms?

dermatologic disease that may or may not include liver and nervous system

31

What enzyme do RBCs contain that is needed for CO2 transport?

Carbonic anhdrase, RBCs carry bicarb

32

Hemoglobin vs myoglobin

hemoglobin: tetramer, signmoidal cooperative binding of O2
myoglobin: monomer in muscle, stores O2, normal binding curve/hyperbolic

33

What is methemoglobin?

Ferric form of hemoglobin

34

R vs T state

R: relaxed, high affinity for O2
T: taut, low affinity for O2

35

What effect does CO have on hemoglobin?

much higher affinity than O2
causes all four subunits to lock in R conformation, limiting O2 release

36

What allosteric regulators can reduce Hb affinity for O2?

H+, CO2, 2,3 DPG
(if O2 is high equilibirium is driven to the right and these will dissociate as Hb binds O2)

37

What are H+ and CO2 classified as in regards to their effect on hemoglobin?

heterotropic negative allosteric effectors

38

What is O2 classified as in regards to it's effect on hemoglobin?

positive homotropic allosteric effector (basis for O2 binding cooperativity)

39

How does 2,3 DPG work?

binds a site in central caity between the beta subunits, stabilizes T state, w/o Hb would have binding curve like myoglobin

40

What can cause an increase of 2,3 DPG?

high altitude, anemia, smoking

41

What affect does temperature have on O2 affinity?

incrased temperature, decreased O2 affinity (useful for O2 unloading w/fever)

42

Where are alpha globin genes located? how many?

chrom 16
4 total, 2/chrom

43

Where are beta globin genes located? how many?

chrom 11
2 total, 1/chrom

44

What are HbA, HbA2 & HbF, respectively?

a2B2, a2d2, a2g2

45

What is the mutation in sickle cell anemia? what does this cause?

Valine substituted for glutamic acid at AA6
valine causes sticky patch on deoxyHb, leads to polymerizatoin into long chains, causes sickle shape, decreased deformability and problems in microcirculation

46

What is HbS?

2 normal alpha chains, 2 sickle adult beta chains

47

What 3 variables does polymer formation depend on?

1. degree of deoxygenation
2. intracellular hemoglobin concentration
3. relative amount of HbF present

48

Beta Thalassemia

major: severe transfusion dependent anemia
two Affected alleles
minor: heterozygote have a mild asymptomatic microcytic anemia

49

alpha thalassemia

caused by mutations that result in reduced or absent synthesis of alpha globin chains
unpaired beta chains are more soluble than unpaired alpha chains, thus effects less severe than in beta thalassemias