Heme

Question 1

pyrophyrias

Answer 1

-diseases associated with defects in heme synthesis

Question 2

jaundice in newborns

Answer 2

-defects in heme breakdown

Question 3

porphin is composed of what

Answer 3

• 4 pyrroles

- porphyin ring is the same in all porphyrins

Question 4

what is heme in chemical terms

Answer 4

-a protoporphyrin with an iron atome

Question 5

what distinguishes the porphyrins?

Answer 5

the sidechains on the pyrrole

Question 6

how do type 1 and type 3 porphyrins differ

Answer 6

• 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

Question 7

problems with protoporphyrinogen 3

Answer 7

• 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

Question 8

protoporphyrin

Answer 8

this is the porphyrin of heme

-oxidized and has side chains

Question 9

heme is required for what molecules

Answer 9

• hemoglobin (most of the heme made is used for this and is made in pre-RBC cells
• cytochromes
• catalase
• peroxidase

Question 10

aminolevulinate synthase

Answer 10

• 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

Question 11

co synthase deficiency

Answer 11

• 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

Question 12

ALAS1 inhibitors

Answer 12

• found in the liver
• heme: allosteric, decreased mRNA stability, inhibits ALAS1 transport into mitochondria
• insulin: decreases transcription of ALAS1

Question 13

ALAS1 promoters

Answer 13

• found in the liver
• steroid hormones: increases ALAS1 expression
• cyt p450: upregulate heme synthesis

Question 14

ALAS2 inhibitors

Answer 14

• found in bone marrow

- heme: inhibits transport into the mitochondria

Question 15

ALAS2 promoters

Answer 15

• 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

Question 16

prophyrias

• mech
• therapy
• important management

Answer 16

• 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

Question 17

porphyria cutanea tarda

Answer 17

• vampires

- deficiency in uroporphyrin decarboxylase