Porphyrins and Hemoglobin

Question 1

porphyrin basic structure

Answer 1

Cyclic
4x pyrrole rings
joined by methine bridges
Intermediates in heme synthesis. myoglobin, cytochromes

Question 2

Porphyrias

Answer 2

Rare disorders resulting from disturbances in heme synthesis

Question 3

Defects
Hemoglobinothapthies vs. thalaseemias

Answer 3

Hemoglobinopathies: Qualitative defects in the molecules
Thalassemias: Quantitative defects in the molecules

Question 4

Myoglobin found in..

Answer 4

Cardiac and skeletal muscle tissues

Question 5

Porphyrin isomers

Answer 5

4 isomers per porphyrin compound
type I/II occur naturally
Type III forms Heme
Sometimes Type I found in excess

Question 6

Porphyrin color

Answer 6

Photoactive
absorb @ 400 nm/emit @ 600-650 nm

Question 7

Uroporphyrin

Answer 7

8 carboxylic groups
Most soluable
Excreted renally

Question 8

Coproporphyin

Answer 8

4 carboxylic acid constituents
intermediate solubility
blood, urine, feces

Question 9

Heme made per ALA

Answer 9

1 heme per 8 ALA

Question 10

reaction locations for heme production

Answer 10

First and last 3: mitochondrion
all others: cytosol

Question 11

Heme controlled through __________

Answer 11

negative feedback loop

Question 12

Neuropsychiatric symptoms

Answer 12

Ab. pain, nausea, hypertension, paresthesia, etc
Excess of early precursors (ALA, PBG)
Porphyrias: ADP, AIP

Question 13

Cutaneous symptoms

Answer 13

Excess porphyrin intermediates
Conditions: CEP, PCT, EPP,XLP
Fragility of skin: CEP/PCT
Burning of skin: EPP/XLPP

Question 14

Neurocutaneous symptoms

Answer 14

excess precursor/intermediates
porphyrias: HCP, VP

Question 15

Acute porphyrias

Answer 15

Serious acute attacks
ADP, AIP: Neuropsychiatric
HCP, VP: neurocutaneous
AIP most common

Question 16

Non-acute porphyrias

Answer 16

CEP,PCT, EPP, XLPP
PCT most common
CEP - extreme photosensitivity

Question 17

Acute porphyrias testing

Answer 17

PBG in urin
if pos -> measure PBG to ID AIP
Fecal for AIP, VP, HCP

Question 18

Cutaneous Porphyrias

Answer 18

Porphyrin in random/timed urine
urine -> PCT/CEP
Plasma/whole blood -> EPP/XLPP

Question 19

Watson-Schwartz assay

Answer 19

Ehrlich’s reagent
max of 555nm

Question 20

HPLC

Answer 20

Porphyrin intermediates in urine

Question 21

Chromatographic analysis

Answer 21

IDs CEP

Question 22

fecal HPLC

Answer 22

differentiates acute AIP, HCP, VP

Question 23

Hemoglobin alpha genes

Answer 23

Chromosome 19

Question 24

Hemoglobin non-alpha genes

Answer 24

chromosome 11

Question 25

Hgb Lepore

Answer 25

Delta beta globin chain

Question 26

HGB Kenya

Answer 26

Gama beta globin chain

Question 27

Hemoglobinopathy Groups Amino acid sub

Answer 27

Hgb S, C ,D, E, O, G

Question 28

Hemoglobinopathy Groups Amino acid deletion

Answer 28

3 or multiples of 3 nucleotides Hgb Gun Hill

Question 29

Hemoglobinopathy Groups Elongated globin chains

Answer 29

Chain termination, frame shift Constant Spring

Question 30

Hemoglobinopathy Groups fused or hybrid chain

Answer 30

nonhomologous crossover Lepore and Kenya

Question 31

normal heme synthesis

Answer 31

Heme in the mitochondria globin in the cytoplasm adequate iron supply

Question 32

Hemoglobin S

Answer 32

6th position glutemic acid swapped for valine HbAS: sickle cell trait HbSS: sickle cell disease

Question 33

Hbg S testing

Answer 33

Solubility test (nonspecific) Cellulose acetate with alkaline pH

Question 34

Hbg C

Answer 34

6th position swapped for lysine Target cells and crystal structures

Question 35

Hgb C testing

Answer 35

Cellulose acetate. Moves with Hgb A2 Negative solubuility test

Question 36

Hgb SC

Answer 36

Most common mixed hemoglobinopathy No normal B chains bird cells

Question 37

Hgb SC testing

Answer 37

Pos solubility testing Cellulose acetate - equals amounts Hgb S and C

Question 38

Hgb E

Answer 38

26th position swap of lysine for glut. acid Microcytes and target cells

Question 39

Hgb E testing

Answer 39

Cellulose acetate - E moves with A2, C, O Citrate agar - E migrates w/ A

Question 40

Hgb D

Answer 40

121st position glysine subbed for glut. acid

Question 41

Hgb D testing

Answer 41

Cellulose acetate - D migrates w/ S citrate agar - D migrates w/ A

Question 42

Thalassemia

Answer 42

Reduced production of chains, but normal function

Question 43

Thal Minor

Answer 43

Heterozygous, asymptomatic, looks like iron deficiency

Question 44

Thal Major

Answer 44

Usually lethal before birth or shortly after

Question 45

Alpha thals

Answer 45

Chromosome 16, total of 4 genes Hydrop Fetalis - most severe. Hgb Bartz, tot. absence of a-chain. Stillborn Hgb H - a chain synth , .5 B chain synth. Moderate hemolytic anemia a-thal trait - two gene deletions. Micro/hypo anemia silent carrier - missing 1 gene. normal production

Question 46

B-thal

Answer 46

caused by gene mutation vice deletions homozygous - Cooley's anemia B+ -> reduced chain prod B0 -> no B-chains

Question 47

Analytical methods for porphyrins

Answer 47

Cellulose acetate EP - alkaline buffer (8.4-8.6) Citrate agar - acid pH (6-6.2) Hgb A2 quantification Acid Elution for Hgb F - the baby vs mom staining

Question 48

DNA testing

Answer 48

Definitive test for thals and hemopath. Specifics: gap-PCR HRM MLPA ASO SSCP NGS Don't worry too much about memorizing just kinda toss it around in the ol' noggin

Question 49

Review EP slides

Answer 49

Just do it. Slides 46/47

Question 50

Myoglobin

Answer 50

Skeletal and cardiac muscle only release on low O2 Tension 1 polypeptide and 1 heme group main role: xport O2 from muscle membrane to mitochondria

Question 51

Utility os myoglobin testing

Answer 51

muscle (cardiac) damage Rhabdomylosis MI muscular dystrophy