Term
*Describe the biochemistry of heme synthesis & degradation*
-in blood cells
-liver
-intestine
-kidney |
|
Definition
IN BLOOD CELLS:
Hemoglobin -> heme, globin
Heme --heme oxygenase--> biliverdin
Biliverdin --biliverdin reductase--> bilirubin (water-insoluble)
Bilirubin carried via blood to the liver
LIVER:
Bilirubin --2 UDP glucoronic acid--> bilirubin diglucuronide (water-soluble)
Bilirubin diglucuronide carried via bile duct to intestines
INTESTINE:
Urobilinogen formed by bacteria
->stercobilin excreted in feces
Urobilinogen reabsorbed into blood
KIDNEY:
-> urobilin excreted in urine |
|
|
Term
| Recognize the important enzymes in the regulation of heme synthesis, delta-aminolevulinate synthase (dALA), ALA dehydratase (ALA DH), and uroporphyrinogen I synthase (UPS), ferrocheletase |
|
Definition
in first step of heme synthesis, glycine + succinyl CoA --> d-ALA
2 d-ALA --ALA DH--> porphobilinogen
UPS is an enzyme involved in the series of rxns that form protoporphyrin IX
4 porphobilinogens ----> porphyrin
Ferrocheletase is the key enzyme that turns protoporphyrin IX -> heme |
|
|
Term
| Describe the pathway of porphyrin in hemoglobin synthesis |
|
Definition
Four porphobilinogens form the first in a series of porphyrins (hydroxymethylbilane, uroporphyrinogen III, coproporphyrinogen III, and protoporphyrinogen IX)
The porphyrins are altered by decarboxylation and oxidation, and protoporphyrin IX is formed
Protoporphyrin IX binds Fe2+, forming heme |
|
|
Term
|
Definition
| Result from deficiencies in the hemoglobin synthesis pathway |
|
|
Term
| Spleen & hemolysis of red cells |
|
Definition
| In hemolysis of red cells in the spleen and liver, macrophages attach to old RBCs and phagocytize them |
|
|
Term
|
Definition
damage to the brain centers of infants caused by increased levels of unconjugated bilirubin
BBB is immature in newborns; bilirubin penetrates, deposits in gray matter, can lead to brain damage or death |
|
|
Term
| Define the role of UDP-glucuronyl transferase |
|
Definition
Conjugating enzyme in the liver
converts unconjugated bilirubin (insoluble) to conjugated bilirubin (soluble) |
|
|
Term
| Describe the formation, excretion, and reabsorption of urobilinogen |
|
Definition
Water-soluble bilirubin diglucuronide is carried in the bile from the liver to the intestine, where it is transformed by bacteria into urobilinogen
Urobilinogen is excreted as stercobilin in the feces, and as urobilin in the urine |
|
|
Term
| Define urobilin, stercobilin |
|
Definition
Both form from urobilinogen
Urobilin: from kidneys, excreted into urine
Stercobilin: formed by bacteria in intestines, excreted in feces |
|
|
Term
|
Definition
| premature destruction of red cells before the usual life span |
|
|
Term
| Differentiate intravascular hemolysis (circulating in the vessels) from extravascular hemolysis in phagocytosis (especially phagocytes in spleen) |
|
Definition
IH: RBCs lyse in the circulation releasing Hb into plasma
-causes mechanical trauma, complement fixation, other toxic damage to RBC
-schistocytes!
-diffuse narrowing of microvasculature with fibrin deposition
-prosthetic heart valve with turbulent blood flow and shear forces
-hemoglobin-haptoglobin...
-hemoglobinemia, hemoglobinuria
-free Hb --> MHb
-free heme groups -> bilirubin -> jaundice
-when liver is normal, jaundice is rarely severe
-within a few hrs, the plasma in a sample of centrifuged blood is clear and pink-red if significant IH (hemoglobinemia) - think transfusion rxn (antibodies coat RBC)
EC: in spleen, results in recycling of AA and iron
-spherocytes! |
|
|
Term
| Unconjugated vs conjugated hyperbilirubinemia |
|
Definition
| Unconjugated hyperb: results from hemolytic anemia, conjugation mechanism in liver is overwhelmed |
|
|
