Term
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Definition
| contain 4 pyrrole rings linked together to form a macrocyclic compound that binds iron at the center. = tetrapyrroles |
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Term
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Definition
| iron protoporphyrin IX. most abundant tetrapyrrole in vertebrates |
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Term
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Definition
| glycine+succinylCoA>ALA (delta-aminolevulinic acid). catalyzed by ALA synthase which requires pyridoxal phosphate and is inhibited by heme. (committed and rate-limiting step of hepatic porphyrin synthesis, takes place in the mitochondria.) |
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Term
| heme synthesis steps 2 on |
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Definition
| 2ALA> porphobilinogen (in cytosol, inhibited by lead). 4 porphobilinogens>hydroxymethylbilane, which is cyclized to produce uroporphyrinogen III. side chain modifications > protoporphyrin IX. |
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Term
| when does heme become heme? |
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Definition
| when iron joins with protoporphyrin IX via ferrochelatase. (blocked by lead) |
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Term
| where is heme synthesized |
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Definition
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Term
| regulation of heme synthesis / in bone marrow specifically |
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Definition
| liver's cytochrome P450 monooxidase system consumes heme to detoxify things. drugs that are metabolized in this cycle use up heme. this upregulates ALA synthase. lead, heme inhibit process. / erythropoietin and the availability of iron. |
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Term
| regulation of hemoglobin synthesis |
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Definition
| 2 alpha and 2 beta globin protein chains, each attached to a heme group that can bind oxygen or CO2. *It is crucial to maintain a balanced ratio of the globin protein chains of hemoglobin with heme: excess heme turns off ALA synthase and excess globin turns off globin protein synthesis (and these two also regulate each other= elf2/HCI) |
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Term
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Definition
| is a translation factor that initiates the translation of globin protein and is inactivated when phosphorylated by HCI (heme-controlled inhibitor), which is only active when heme is not available to suppress its function. therefore, low heme leads to the inactivation of globin synthesis. |
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Term
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Definition
| defects in heme synthesis, all autosomal dominant except congenital erythropoietic porphyria. when the accumulated intermediate is a tetrapyrrole, you get photosensitivity. |
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Term
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Definition
| most common of the porphyrias. chronic disease of liver and bone marrow. deficiency of uroporphyrinogen decarboxylase, accumulation of uroporphyrin. dark red urine and photosensitivity. |
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Term
| acute intermittent porphyria |
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Definition
| defect in porphobilinogen deaminase. ALA and porphobilinogen accumulate (no photosensitivy - only one!) = GI pain, neurologic/psychiatric symptoms, cardiovascular symptoms. episodes may be preceded by drugs that consume P450 heme, activating ALA synthesis. (do NOT give phenobarb and send home, it will make it worse.) |
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Term
| erythropoietic protoporphyria |
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Definition
| deficiency in ferrochelatase causes protoporphyrin to accumulate > photosensitivity |
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Term
| congenital erythropoietic porphyria |
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Definition
| defect in uroporphyrinogen III synthase = accumulation of uroporphyrinogen I and coproporphyrinogen I. photosensitivity. |
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Term
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Definition
| 85% of cells programmed to die are at end of 120 day cycle. within splenic macrophage, heme and globin are separated. heme decyclized to biliverdin, which is reduced to bilirubin, which binds to albumin in the blood. hepatocytes conjugate bilirubin with 2molecules glucuronic acid (to improve solubility), releasing bilirubin glucuronide into bile. in intenstine, is metabolized by bacteria to urobilinogen. |
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Term
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Definition
| stercobilin (brown feces) or urobilin (yellow urine) |
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Term
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Definition
| normal bilirubin = 300mg/day, capacity=3000mg/day, but any more lysis and you get jaundice. (ex. sickle cell anemia, g6pd deficiency, pyruvate kinase deficiency) |
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Term
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Definition
| liver damage = more unconjugated bilirubin. stools are pale, urine is dark, patients experience anorexia and nausea. high serum levels of AST, ALT |
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Term
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Definition
| cancer or gall stones in bile duct. abdominal pain and nausea, dark urine, pale stool. |
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Term
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Definition
| first 4wks = can't conjugate bilirubin. if level rises above capacity for albumin to bind this poorly soluble compound in blood, toxic encephalopathy occurs. treat with blue fluorescent light, makes it soluble. |
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Term
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Definition
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Term
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Definition
| oxidases (H2O2), bile pigments, chlorophyll, coenzyme b12 not in humans |
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Term
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Definition
| inhibited by lead; enzyme that binds 2ALA into porphobilinogen |
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Term
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Definition
| heme, glucose. inducted by phenobarb, alcohol, hypoxia. |
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Term
| t/f ferrochelatase allows iron to bind with heme |
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Definition
| false - iron and heme bind spontaneously, but ferrochelatase is a catalyst |
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Term
| excess iron is toxic due to |
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Definition
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Term
| serum iron is complexed to / cellular... |
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Definition
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Term
| carnivores absorb ___ but humans don't as effectively |
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Definition
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Term
| erythropoietic porphyrias |
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Definition
| cutaneous symptoms, appear in early childhood, some complicated by liver cirrhosis |
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Term
| what color is urobilinogen? |
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Definition
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Term
| how are different porphyrins distinguished from one another? |
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Definition
| by types and distribution of side groups |
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