MBC - Lecture 44 Word Scramble
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Question | Answer |
Lecture 44 | Heme Biosynthesis |
___ is the most common porphyrin in the body. | Heme |
Heme is complexed with ___, ___, and ___. | hemoglobin, myoglobin, and cytochromes |
Heme transports ___. | oxygen |
Heme is degraded and excreted in the gut and urine as a conjugate of ___. | bilirubin |
Glycine + Succinyl-CoA → ___ | 5-aminolevulinate (5-ALA)/ δ -aminolevulinate |
5-ALA goes through 7 enzymatic steps to produce ___. | heme |
δ- aminolevulinate synthase (ALAS) contains ___. | pyridoxal phosphate (PLP) |
Lead inactivates the following enzymes: | δ-aminolevulinic acid dehyrdatase, protoporphyinogen oxidase, and ferrochelatase |
Uroporphyrinogen decarboxylase acts on side chains of ___. | uroporphyinogen |
Deficiency of uroporphyrinogen decarboxylase leads to accumulation of ___. | uroporphyrinogen III |
___ inhibits uroporphyrinogen decarboxylase. | Iron salts |
Poryphria Cutenea Tarda | Most common porphyria, light sensitivity, recessive allele leading to 50% reduction of uroporphyrinogen decarboxylase activity with normal hepatic heme production, makes carrier sensitive to alcohol |
Heme biosynthesis begins and ends in the ___. | mitochondria |
Aminolevulinate Synthase (ALAS) | Catalyzes formation of 5-aminolevulinate (ALA) in the mitochondria from glycine and succinyl-CoA |
Aminolevulinate Dehydratase (ALAD) | Catalyzes formation of porphobilinogen (PBG) in the cytoplasm from ALA (aka porphobilinogen synthase) |
Ferrochelatase | Catalyzes formation of heme in the mitochondria by addition of Fe2+ to protoporphyrin |
Under conditions of low iron availability, ___ can be inserted, resulting in a fluorescent molecule. | zinc |
___ is a negative feedback inhibitor of 5-ALAS. | Heme |
3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) inhibits ___. | ferrochelatase |
Porphyria | Partial interruption in heme synthesis leading to excess porphyrin precursors in the liver |
___ and ___ are neurotoxins, measurable in urine. | ALA and porphobilinogen |
Symptoms of porphyria include: | abdominal pain, peripheral neuropathies, respiratory paralysis, and acute psychotic episodes |
Porphyria are often ___, but can be triggered by fasting, dieting, or a chemical/hormone/drug. | asymptomatic |
Heme is degraded to non-soluble ___. | bilirubin |
Heme is cleaved by ___ to form biliverdin. | heme oxygenase |
Biliverdin is reduced by ___ to form bilirubin. | biliverdin reductase |
Bilirubin is transported to the __ by conjugation with ___. | liver, albumin |
Conjugation of bilirubin and ___, making it soluble for excretion in bile. | glucuronic acid |
Glucuronyl Bilirubin Transferase | Catalyzes conjugation of bilirubin with glucuronic acid to form bilirubin diglucuronide |
Bilirubin diglucuronide is released to the intestine and degraded to ___. | urobilinogen |
75% of bilirubin is from ___. | red blood cells (250-350 mg/day) |
Majority is excreted in feces as ___. | stercobilin (brown color) |
Normal bilirubin levels are <___ micromoles per liter. | <17 |
Jaundice is clinically obvious when bilirubin levels are >___ micromoles per liter. | >50 |
Pre-Hepatic Jaundice | Increased bilirubin production by RBC breakage, blood extravasation, sickle cell anemia |
Intrahepatic Jaundice | Inability for liver to uptake, conjugate, or secrete bilirubin |
Post-Hepatic Jaundice | Obstruction of biliary excretion |
Hepatic Failure | Acetaminophen toxicity, 70 micromolar bilirubin |
Neonatal Jaundice | Common 48 hours after birth, after 10 days is abnormal, 150 micromolar bilirubin |
Obstructive Liver Disease | 230 micromolar bilirubin |
___ measured in blood as markers for liver function/damage. | Transaminases |
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