Porphyrins and Hemoglobin

porphyrins

chemical intermediates in the synthesis of hemoglobin, myoglobin, and other respiratory pigments called cytochromes

clinical significance of porphyrins

aid in the diagnosis of porphyrias, which result from disturbances in heme synthesis

significance of elevated porphyrins

indicates a metabolic block in heme synthesis

porphyrins specimen

blood, urine, stool

three porphyrin compound

protoporphyrin (PROTO) → stool

uroporphyrin (URO) → urine

coproporphyrin (COPRO) → urine and stool

elevated levels indicate abnormal heme synthesis

two main sources of porphyrin synthesis

liver and bone marrow

porphyria

enzyme deficiencies that result in overproduction of heme precursors in the bone marrow or liver

hemoglobin role

transport oxygen and carbon dioxide

hemoglobin structure

hgb = 4 heme + globin

heme = porphyrin ring + iron

globin = 2 pairs of unlike polypeptide chains

hemoglobinopathies

defects in hgb structure

thalassemias

defects in the rate and quantity of hgb production

four possible types of abnormal globin production

1. amino acid substitution

2. amino acid deletion

3. elongated globin chains (termination, frame shift)

4. fused/hybrid chains from chromosomal crossovers

two major categories of thalassemias

alpha thalassemia: alpha globin chain absent

beta thalassemia: beta globin chain absent

three factors hgb production depends on

adequate iron supply

normal heme synthesis

normal globin synthesis

transferrin

plasma protein that transports iron to immature RBCs in bone marrow

haptoglobin

plasma protein that prevents plasma hgb loss through renal excretion

qualitative defect

defect in structure (hemoglobinopathies)

quantitative defect

defect in rate of synthesis (thalassemias)

most common hemoglobinopathies

Hgb S, hgb C, hgb SC

thalassemic RBC morphology

microcytic and hypochromic

thalassemia minor

heterozygous thalassemia, mimics iron deficiency, one type of globin chain synthesis is affected 

thalassemia major

homozygous thalassemia, severe and lethal, both globin chain synthesis affected

myoglobin

heme protein found in skeletal and cardiac muscle

used to dx MI and muscle wasting disorders