Term
| The first step of heme synthesis requires _________ as reactants, _______ as a cofactor, ________ as an enzyme and produces_________. |
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Definition
1. Succinyl-CoA and Gly
2. vitamin B6 (pridoxal)
3. ALA synthase
4. ALA (levulinic acid) |
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Term
| What is the committed step of Heme synthesis? |
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Definition
| The first step- the formation of ALA, is the the committed step. |
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Term
| How is Heme production regulated? |
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Definition
| Heme production is regulated by the negative feedback of Heme on ALA synthetase |
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Term
| What is the first (early) site of Pb on Heme synthesis? |
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Definition
| Pb targets the ALA dehydratase enzyme (step 2) |
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Term
| What two enzymes of Heme synthesis does Pb affect? |
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Definition
| ALA synthetase and Ferrochelatase |
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Term
| Many steps of Heme synthesis are compartmentalized. Which ones occur in the mitochondria? |
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Definition
| Steps 1 & 6-8 occur in the mitochondria |
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Term
| How much Heme synthesis occurs in RBCs? |
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Definition
| None, because RBCs do not have mitochondria. However, there is increased Heme synthesis in Reticulocytes |
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Term
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Definition
| Porphyrias are inborn mutations in Heme biosynthesis. The 2 main types are accute intermittent and congenital erythropoietic |
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Term
| Describe accute intermittent porphyria |
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Definition
| Accute Intermittent Porphyria: the problem occurs early in the sequence of Heme biosynthesis -> accumulation of ALA and PBG -> neuropsychiatric symptoms |
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Term
| Describe congenital erythropoietic porphyria |
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Definition
| Congenital Erythropoietic Porphyria: Error occurs later in sequence of Heme biosynthesis. Accumulation of porphyrinogens in skin -> light sensitivity |
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Term
| Porphyrias: no matter where the block in Heme biosynthesis is, porphyrias lead to decreased ______ and, ergo, increased _______ biosynthesis. |
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Definition
1. Heme synthesis
2. ALA and PBG |
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Term
| How is bilirubin transported in the blood? |
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Definition
| Bilirubin is transported to the liver as a bilirubin-albumin complex in the blood |
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Term
| Hemin is degraded by ___________, a complex enzyme in the liver, spleen and bone marrow. |
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Definition
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Term
| Bilirubin breakdown in the gut leads to __________, which is then excreted in urine as _________. |
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Definition
1. Urobilinogen
2. Urobilin |
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Term
| Bilirubin consists of an open chain of four _______ rings. In heme, by contrast, these four rings are connected into a larger ring, called a ___________ ring. |
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Definition
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Term
| Oxidized bilirubin becomes ___________, which has a __________ color. |
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Definition
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Term
| In order to be water soluble, bilirubin must be conjugated with __________. |
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Definition
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Term
| What bilirubin derivative gives feces their brown color? |
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Definition
| Stercobilin (conjugated bilirubin -> mesobilirubinogen -> stercobilinogen -> stercobilin) |
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Term
| The glucuronic acid of conjugated bilirubin is derived from ___________ |
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Definition
| UDP-glucose (converted to UDP glucuronic acid by UDP-Glucose Dehyrdrogenase) |
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Term
| What is the name of the clinical test for serum bilirubin? |
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Definition
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Term
| "direct" bilirubin is a measure of what, and using what solvent? |
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Definition
| "Direct" bilirubin indicates conjugated bilirubin only. The test uses water as a solvent |
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Term
| "Total bilirubin" is a measure of what, and is done with what solvent? |
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Definition
| "Total Bilirubin" gives the amount of all serum bilirub, conjugated + unconjugated. It is done with methanol and water as solvents. |
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Term
| What does "Indirect Bilirubin" measure? |
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Definition
| "Indirect Bilirubin" measures the amount of non-conjugated bilirubin in the blood serum. (Total - direct = indirrect) |
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Term
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Definition
| An accumulation of bile pigments (bilirubin) |
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Term
| Very high levels of non-conjugated bilirubin and a slight increase in conjugated bilirubin indicates ___________ |
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Definition
| High non-conjugated bilirubin and a small conjugated bilirubin increase indicate a PRE-HEPATIC problem, as the ammount of bilirubin in the system is swamping the conjugation system |
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Term
| Very high non-conjugated bilirubin levels with a slight decrease (or no change) in conjugated bilirubin levels indicates ___________ |
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Definition
| This indicates an intra-hepatic problem. There may be a problem with the conjugation mechanism. |
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Term
| A very large incrase in conjugated bilirubin, and a small (or no) change in non-conjugated bilirubin indicates ______ |
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Definition
| This indicates a post-hepatic problem- bilirubin is conju |
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Term
| The inability of neonates to conjugate bilirubin (lack of UDP-glucuronic acid), can lead to what condition? |
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Definition
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