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67 Cards in this Set
- Front
- Back
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what is the most common porphyrin?
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heme
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what kind of rings link to form heme? how many?
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pyrrole rings; 4
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when heme is complexed with proteins to form cytochromes, what are the functions of those cytochromes?
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catalysis and electron transfer
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when heme is complexed with proteins to form peroxidases and catalase, what are the functions of these enzymes?
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decomposition of hydrogen peroxide
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what two compounds are needed to synthesize heme?
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succinyl CoA and Glycine
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synthesis of heme in the liver is produced by what compound? what about in bone marrow?
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cytochrome P450; hemoglobin
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where do the intermediate reactions of the synthesis of heme occur?
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cytosol
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which steps of the heme synthesis take place in the mitochondria?
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initial reaction and last three steps
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which two intermediates of the TCA cycle are responsible for amino acid synthesis?
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alpha-ketoglutarate and oxaloacetate
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which intermediate of the TCA cycle is responsible for FA synthesis?
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citrate
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which intermediate of the TCA cycle is responsible for glucogenesis?
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Malate
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what is the rate-limiting step of heme synthesis?
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succinyl CoA + glycine --> sigma aminolevulinic acid via sigma aminolevulinic acid synthase
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what type of phosphate is required for sigma aminolevulinic acid synthase to work correctly?
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pyridoxal phosphate
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what are the two forms of sigma-ALA in humans? how does the expression of these two forms vary?
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one gene is located on chromosome X synthase and one is linked on chromosome 3 synthase; the one located on chromosome X synthase is expressed in RBC precursors whereas the one located on chromosome 3 synthase is expressed throughout the body.
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mutations in the sigma-ALA on chromosome X synthase can lead to what type of anemia?
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sideroblastic
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how does heme regulate ALA synthase?
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in two ways: 1) by being a negative allosteric regulator and 2) by inhibiting the synthesis of ALA synthase.
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how is the transcription of sigma ALA synthase controlled? what is prevented?
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Iron binding element which prevents excessive formation of porphyrin intermediates when iron is low or absent
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how do many drugs result in increase of hepatic ALA synthase activity?
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the drugs are metabolized in the Cyt P450 monooxygenase system which leads to an increased consumption of heme, increasing the synthesis of ALA synthase.
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what molecule is condensed to form the pyrrole ring?
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delta-ala. Two of them.
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The enzyme that catalyzes the formation of the pyrrole ring is sensitive to inhibition by what? what is the enzyme?
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heavy metals (lead); delta- ALA dehydratase
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which step in the synthesis of heme occurs spontaneously?
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introduction of iron into protoporphyrin 9 - final step
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what inhibits the final step in the heme synthesis pathway? what enhances it?
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lead; ferrochelatase
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what are porphyrias caused by?
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inherited defects in heme synthesis
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what type of genetic disorders are porphyrias? except which one...
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autosomal dominant; erythropoetic protoporphyria which is recessive.
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Porphyrias classified as Hepatic are considered both? what about the ones classified as erythropoetic?
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acute and chronic; usually chronic
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what is the treatment for porphyrias?
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IV injection of hemin
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which two enzymes are particularly sensitive to inhibition by lead?
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Ferrochelatase and ALA dehydrogenase
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what is the enzyme that is deficient in acute intermittent porphyria?
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hydroxymethylbilane synthase
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which porphyrias result in photosensitive patients?
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erythropoietic protoporphyria, varigate porphyria, hereditary coproporphyria, porphyria cutanea tarda, and congenital erythropoeitic porphyria
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which porphyria does NOT accumulate its backed up intermediate into the urine?
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erythropoeitic protoporphyria
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what is the most common porphyria? what color is the urine?
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porphyria cutanea tarda; orange
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a patient comes in for a routin urine sample, the lab tech accidentally forgets to cap the urine sample and comes back to a container of black urine. What porphyria does this patient have?
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acute intermittent porphyria
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What is the lifespan of an RBC in the blood stream?
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60-120 days
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Into what system do RBCs go to die?
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reticuloendothelial system
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T/F
RBC phagocytosis occurs intravascularly in the blood stream and lysis occurs extravascularly in the reticuloendothelial system. |
FALSE.
Extravascularly - reticuloendothelial system by phagocytosis Intravascularly - lysis in blood stream |
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what are the three purposes of free intravascular hemoglobin?
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scavenge iron, prevent major iron losses and complex free heme (very toxic).
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where is the hemoglobin-haptoglobin complex metabolized? what does it form? what is its job?
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liver and spleen; iron-globin complex and bilirubin; prevents loss of iron in urine
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what does hemopexin bind? where is the complex taken up? How is iron stored?
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free heme; liver; bound to ferritin
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where does 75% of the heme come from?
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RBCs
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what is the normal daily load of bilirubin?
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250-300 mg
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what is the fate of both heme and globin when hemoglobin is degradation?
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heme is oxidized to bilivderin which is reduced to bilirubin and transported to the liver via albumin and globin is cleaved to amino acid.
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if the liver cannot properly transport, store or conjugate bilirubin, where does bilirubin accumulate?
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in the blood and certain areas of the brain
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what changes between a bilirubin molecule and a conjugated bilirubin molecule?
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a conjugated bilirubin molecule has two glucuronate residues transferred to the bilirubin. This makes the molecule more soluble for transportation and excretion.
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what are the three types of jaundice?
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prehepatic, intrahepatic and posthepatic
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what is the cause of prehepatic jaundice?
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hemolysis
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what are the 6 causes of intrahepatic jaundice?
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infection, chemical/drug, genetic errors: bilirubin metabolism, genetic errors: specific proteins, autoimmune and neonatal
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what are the 2 posthepatic causes of jaundice?
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intrahepatic bile ducts and extrahepatic bile ducts
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what converts conjugated bilirubin to urobilnogen?
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bacteria in the gut
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what are three possible results of excess RBC lysis?
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autoimmune disease, hemolytic disease of the nerbown and structurally abnormal RBCs
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intrahepatic jandice occurs due to the....
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impaired uptake, conjugation or secretion of bilirubin
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what is significant about the fecal matter and urine of the patient with posthepatic jaundice?
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pale colored stools (absence of fecal bilirubin and urobilin) and dark urine (increased conjugated bilirubin)
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In a complete obstruction of the biliary tree, what is absent from the urine?
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urobilin
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what is absent from the urine of a person with prehepatic jaundice?
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bilirubin
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T/F
Conjugated hyperbilirubinemis has less severe symptoms than unconjugated. |
TRUE!
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what is cringer-najjar syndrome?
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autosomal recessive disorder characterized by a complete absence or marked reduction in bilirubin conjugation.
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when do the symptoms of cringer-najjar syndrome usually assert themselves?
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at birth with a sever unconjugated hyperbilirubinemia.
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which populations have a higher incidence rate?
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amish and mennonites
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the individuals afflicted with cringer-najjar syndrome are at high risk for what? how are these individuals treated?
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kernicterus; phototherapy (10-12 hrs/day) and liver transplant by age 5
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what does dubin-johnson syndrome result from?
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mutations in the bile canalicular multispecific organic anion transporter. This transporter is involved in the excretion of many non-bile organic anions by an ATP requiring precess.
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why does the liver turn black in pts with dubin-johnson syndrome?
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lysosomal accumulation of pigment due to the mutations in the bile canalicular multispecific organic anion transporter.
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what differentiates rotor syndrome from dubin-johnson?
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The liver is not pigmented in Rotor syndrome.
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what differentiates Gilbert's syndrom from Crigler-najjar syndromes type 1 and 2?
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Gilbert's syndrome is more prevalent (5-10% of population vs 1/ 1 mil), the activity of glucuronyl transferase is higher in Gilbert's (25-30% vs 10% or absent), and the uncojugated bilirubin of crigler-najjar syndrome has to be above or below 375 vs the no specifications for Gilbert's syndrome besides unconjugated bilirubin.
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what is the percentage of newborns that develop neonatal jaundice?
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60%
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what drug is often given to mom prior to an induced labor of a premature infant? how does it work?
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phenobarbital; drug crosses the placenta and induces the synthesis of UDP glucuronyl transferase
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what is jaundice classified as pathological in babies?
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if it occurs within the first 24 hrs of life or takes longer than 10 days to resolve.
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what reaction is used to determine bilirubin concentration?
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Van der bergh
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what do you add to measure the total bilirubin as opposed to just the conjugated bilirubin?
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alcohol
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