Term
| Name the tissues where heme biosynthesis is highest and indicate the major use of heme in those tissues |
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Definition
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Term
| Describe the general structural features of heme |
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Definition
| 4 pyrrole groups joined by bridging Carbons; N atoms coordinate the Ferrous ion in the middle; |
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Term
| Name the two simple molecules that contribute all the atoms for the organic portion of heme |
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Definition
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Term
| Describe the first step in heme biosynthesis, indicating the product of the reaction and the enzyme responsible |
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Definition
-Glycine + Succinyl CoA -> Delta-Aminolevulinic acid (ALA)
- enzyme is ALA synthase
- takes place in the mitochondria |
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Term
| Describe the differences between prophyrinogen intermediates and porphyrins and indicate whether or not porphyrinogens can be non-enzymatically converted to porphyrins |
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Definition
Porphyrinogens
• no double bonds at the bridging carbons
• colorless
Porphyrins
• double bonds at the bridging carbons
• colored, highly fluorescent, photodegradable
Porphyrinogens can be non-enzymatically oxidized to
porphyrins by light |
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Term
| Describe how heme biosynthesis is regulated in the liver |
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Definition
| - Heme acts via negative feedback on ALA synthase |
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Term
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Definition
| disease caused by a partial deficiency of one of the enzymes involved in heme biosynthesis |
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Term
1. Indicate which two intermediates of hemebiosynthesis are increased in acute intermittent porphyria
2. Which factors exacerbate the disease by inducing ALA synthase?
3. How can the feedback inhibition by heme be used in treatment? |
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Definition
-ALA and Porphobilinogen (PBG deaminase deficiency)
- reduction of heme decreases the feedback inhibition of ALA synthase, so even more ALA and Porphobilinogen is made
- intravenous administration of heme to suppress ALA synthase |
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Term
| What causes photosensitivity seen in many porphyrias |
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Definition
the accumulation of substances, such as porphyrinogens and porphyrins, that are reactive to light
- porphyrinogens can be turned into porphyrins by light and porphyrins are degraded by light |
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Term
| Name the cells that are primarily responsible for the degradation of hemoglobin |
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Definition
| -phagocytic cells of the reticuloendothelial system |
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Term
| Describe the fate of constituents of hemoglobin: globin, iron, and porphyrin |
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Definition
globin > free amino acids
iron > reutilized
heme > bilirubin > degraded |
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Term
| Name the products of porphyrin degradation by heme oxygenase and biliverdin reductase (Provide an alternate name for the second product) |
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Definition
-heme oxygenase catalyzes the formation of biliverdin
-biliverdin reductase catalyzes the formation of unconjugated bilirubin or "indirect bilirubin" |
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Term
| Describe how unconjugated bilirubin is carried in the plasma |
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Definition
| -as a complex with albumin |
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Term
| Describe the processes of uptake and conjugation of bilirubin and the secretion of conjugated bilirubin by the liver |
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Definition
- taken up in liver by active transport
- 2 glucuronic acid groups are attached to the unconjugated bilirubin to form a soluble conjugated bilirubin (bilirubin diglucuronide)
- conjugated bilirubin is actively secreted into the bile canaliculus |
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Term
| Define hyperbilirubinemia |
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Definition
-elevated bilirubin in serum (>1mg/dL)
-can be conjugated or unconjugated form, or both
-can lead to jaundice |
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Term
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Definition
- occurs when elevated bilirubin diffuses into tissues, making them appear yellow
- detectable when serum bilirubin reaches 2-2.5mg/dL |
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Term
| Define the clinical consequences of hyperbilirubinemia |
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Definition
-conjugated- benign, no toxic effects
-unconjugated- toxic to brain at conc. >25mg/dL ; if albumin is saturated, then the free floating unconjugated bilirubin can travel to the brain; as long as it is bound to albumin it cannot get to the brain |
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Term
| Describe some causes of hyperbilirubinemia |
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Definition
1. Hemolytic anemia
2. Hepatitis or cirrhosis
3. Bile duct obstruction- conjugated bilirubin can't be delivered to the intestine, so it will back up
4. Neonatal "physiological jaundice" |
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