Flashcards in Hem & Onc - Pathology (Heme synthesis, porphyrias, & lead poisoning) Deck (17):
What 2 enzymes are affected by lead poisoning? What is the accumulated substrate in each instance? Where do they accumulate?
(1) Ferrochetelase - accumulation of protoporphyrin (2) ALA dehydratase - accumulation of delta-ALA; blood
What are the presenting symptoms of lead poisoning in general? What about specifically in children? What about specifically in adults?
Microcytic anemia, GI & kidney disease; Children - exposure to lead paint --> mental deterioration; Adults - environmental exposure (battery/ammunition/radiator factory) --> headache, memory loss, demyelination
What are the exposures for lead poisoning seen in children versus adults?
Children - lead paint; Adults - environmental exposure (e.g., battery/ammunition/radiator factory)
What is the affected enzyme in acute intermittent prophyria? What substrate(s) accumulate(s) as a result? Where does it/they accumulate?
Porphobilinogen deaminase; Porphobilinogen, delta-ALA, coporphobilinogen (urine)
What are the symptoms associated with acute intermittent porphyria?
(1) Painful abdomen (2) Port wine-colored urine (3) Polyneuropathy (4) Psychological disturbances (5) Precipitated by drugs, alcohol, and starvation; Think: "5 P's"
What is the treatment for acute intermittent porphyria, and why?
Glucose and heme, which inhibit ALA synthase
What is the affected enzyme in porphyria cutanea tarda? What substrate(s) accumulate(s) as a result? Where does it/they accumulate?
Uroporphyrinogen decarboxylase; Uroporphyrin; Urine = tea-colored
What are the signs/symptoms associated with porphyria cutanea tarda?
Blistering cutaneous photosensitivity, tea-colored urine
What is the most common porphyria?
Prophyria cutanea tarda
What is the rate-limiting step of the heme synthesis pathway?
dela-aminolevulinic acid synthase catalyzes the conversion of glycine + succinl-CoA to delta-aminolevulinic acid
What is the first step in the heme synthesis pathway? Where does it take place? What enzyme catalyzes this step?
Conversion of glycine + succinl-CoA to delta-aminolevulinic acid; Mitochondria; dela-aminolevulinic acid synthase
What 4 steps of the heme synthesis pathway take place in the cytoplasm? What enzymes catalyze them?
(1) delta-aminolevulinic acid (synthesized in mitochondria during first step of heme synthesis pathway) converted to porphobilinogen by delta-aminolevulinic acid dehydratase (2) Porphobilinogen converted to hydroxymethylbilane by Porphobilinogen deaminase (3) Hydroxymethylbilane converted to Uroporphyrinogen III (no enzyme specified in First Aid) (4) Uroporphyrinogen III converted to Coproporphyrinogen III by Uroporphyrinogen decarboxylase
Where is protoporphyrin synthesized, and from what precursor in the heme synthesis pathway?
Mitochondria; Coproporphyrinogen III
What is the final step in the heme synthesis pathway? Where does it take place? What enzyme catalyzes it?
Iron added to Protoporphyrin to synthesis Heme; Mitochondria; Ferrochetalase
What effect do low versus high heme levels have on ALA synthase activity?
Low heme --> increased ALA synthase activity; High heme --> decrease ALA synthase activity
Draw out the steps of the heme synthesis pathway, including precursors, enzymes, and locations of each major step.
See p. 388 in First Aid 2014 for visual at bottom of page