Heme Flashcards
1
Q
pyrophyrias
A
-diseases associated with defects in heme synthesis
2
Q
jaundice in newborns
A
-defects in heme breakdown
3
Q
porphin is composed of what
A
- 4 pyrroles
- porphyin ring is the same in all porphyrins
4
Q
what is heme in chemical terms
A
-a protoporphyrin with an iron atome
5
Q
what distinguishes the porphyrins?
A
the sidechains on the pyrrole
6
Q
how do type 1 and type 3 porphyrins differ
A
- 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
Q
problems with protoporphyrinogen 3
A
- 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
Q
protoporphyrin
A
this is the porphyrin of heme
-oxidized and has side chains
9
Q
heme is required for what molecules
A
- hemoglobin (most of the heme made is used for this and is made in pre-RBC cells
- cytochromes
- catalase
- peroxidase
10
Q
aminolevulinate synthase
A
- 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
Q
co synthase deficiency
A
- 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
Q
ALAS1 inhibitors
A
- found in the liver
- heme: allosteric, decreased mRNA stability, inhibits ALAS1 transport into mitochondria
- insulin: decreases transcription of ALAS1
13
Q
ALAS1 promoters
A
- found in the liver
- steroid hormones: increases ALAS1 expression
- cyt p450: upregulate heme synthesis
14
Q
ALAS2 inhibitors
A
- found in bone marrow
- heme: inhibits transport into the mitochondria
15
Q
ALAS2 promoters
A
- 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
Q
prophyrias
- mech
- therapy
- important management
A
- 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
Q
porphyria cutanea tarda
A
- vampires
- deficiency in uroporphyrin decarboxylase
