Flashcards in Heme Deck (17)
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1
pyrophyrias
-diseases associated with defects in heme synthesis
2
jaundice in newborns
-defects in heme breakdown
3
porphin is composed of what
-4 pyrroles
-porphyin ring is the same in all porphyrins
4
what is heme in chemical terms
-a protoporphyrin with an iron atome
5
what distinguishes the porphyrins?
the sidechains on the pyrrole
6
how do type 1 and type 3 porphyrins differ
-type 3 is physiologic, its ring D is asymmetric to the other rings
-type 1 is a harmful biproduct which can result from deficiencies in heme synthesis
7
problems with protoporphyrinogen 3
-intermediates in heme synthesis
-can spontaneously oxidize and creat protoporhpyrin which is a conjugated double bond system
-can cause deposits in the skin, photosensitivity, and neurotoxicity
-oxidized product is insoluble, difficult to excrete
8
protoporphyrin
this is the porphyrin of heme
-oxidized and has side chains
9
heme is required for what molecules
-hemoglobin (most of the heme made is used for this and is made in pre-RBC cells
-cytochromes
-catalase
-peroxidase
10
aminolevulinate synthase
-this is the first step in heme prduction
-heavily regulated
-occurs in the mitochondria
-condenses glycine and succinyl CoA to make delta ALA
-slowest reaction in heme synthesis
-product is transported to the cytoplasm
11
co synthase deficiency
-this enzyme is typically responsible for uroporphyinogen type 3
-if defficient, uroporphyrinogen type 1 is formed which can be converted to coprophorynogen type 1
-these can be oxidized into conjugate double bond systems which deposit in the skin causing photosensitivity and is neurotoxic
12
ALAS1 inhibitors
-found in the liver
-heme: allosteric, decreased mRNA stability, inhibits ALAS1 transport into mitochondria
-insulin: decreases transcription of ALAS1
13
ALAS1 promoters
-found in the liver
-steroid hormones: increases ALAS1 expression
-cyt p450: upregulate heme synthesis
14
ALAS2 inhibitors
-found in bone marrow
-heme: inhibits transport into the mitochondria
15
ALAS2 promoters
-found in the bone marrow
-iron: increase translation of ALAS2 by removing an inhibitor from mRNA
-increase ferrochelatase activity
-transcription factors: coordinate globin genes and ALAS2 transcription
16
prophyrias
-mech
-therapy
-important management
-accumulation of toxin intermediates up to a point of a defect
-treated by decreasing activity of ALAS (can not give patient steroid hormones)
-important to eliminate conditions leading to increased use of free heme, CYPP450 reactive drugs
17
