Heme Biosynthesis Flip Class

Question 1

Structure of heme

Answer 1

4 pyroles (pent with N at top and two double bonds)

Either methyl, vinyl, or propionate
-arrangement of side chains is important for activity

Fe+2

Question 2

Heme aka

Answer 2

Protophyrin IX

Question 3

p450 class enzymes

Answer 3

Synthesized by heme

In liver-liver detox, synthesis of vit D, cholesterol syn, synthesis of bile and bile acids

Decrease in these enzymes leads to heme biosyn

Incrased sun after 4M

Question 4

Porphyrin precursors

Answer 4

ALA and PBG

Water soluble and are excreted and measured in urine

Question 5

Porphyrinogens

Answer 5

Larger-aqueous stability varies based on number of carboxylic acid (acidic) side chains

Biologiacally active

Reduced

Question 6

Porphyrins

Answer 6

Detected and measured in a labs

Oxidized-creates conjugation system that allows molecules to abosrt visible light
-Produces reactive species in tissue

Question 7

Heme biosynthesis pathway

8 steps

Answer 7

Succinyl CoA+glycine
-delta aminolevunlinic acid synthase
2 Delta aminovulnic acids
-delta aminovulinic acid dehhydratase
4 Porphobilinogen
-Porphobilinogen deaminase
Hyroxymethbilane
-UROIII Cosynthase
UROIII
-URO Decarboxlyase
COPROIII
-Copro Oxidase (all phyrinogen above)
Protophyrinogen IX
-Proto oxidase
Protophyrin 9
-Ferrochelatase and Fe2+
Heme

Question 8

what parts of heme biosyn are in mito

Answer 8

succinyal coa and glycine to ALA
and
Copro III to Heme

Question 9

ALAS=

Answer 9

Vit B6

Pyridoxal phosphate

Question 10

Committed step?

Answer 10

ALAS

Question 11

Inhibited by Fe

Answer 11

ALAS II

Question 12

Inhibited by Pb

Answer 12

ALAD, Ferro (less sensitive), Pyrimidine 5’ nucleotides

Question 13

Where is heme syn?

Answer 13

Bone marrow (85%)
Liver

Question 14

What stops heme syn

Answer 14

RBC mature

Question 15

1st step

Answer 15

Sucinyal CoA and glycine to delta Aminivulinate

b6

ALAS1 or housekeeping in liver
ALAS2 (inhabit by Fe)

Question 16

1st step inhib

difference with ALASII

Answer 16

hematin, hemin heme,(allosteric inhib)

Heme (inhibits alas to cyto)

Heme, insulin , glucose-repress trx of ALAS

Has IRE-translation blocked by Pb

Question 17

2nd step

Answer 17

2 molecules ALA to PBG by ALAD

ALAD contains Zn

1st precursor pyrole

Inhibited by Pb

Question 18

1st step activation

Answer 18

4M

Liver-metabolize p450 stuff

induce sun of p450-need heme

decrease concentration of heme in cells

Question 19

4m

Answer 19

meds, maladies, bleeding, malnutrition

increase p450 sun

Question 20

3rd step

Answer 20

4PBG+PBGD=HMB

Question 21

4th step

Answer 21

HMB+UROIIIS=UROIII+UROIIID=COPROI
or
high conc
HMB spont to UROI spont to COPROI

Question 22

URO III, COPROIII, Protophyrinogen IX

excretion

Answer 22

urine, urine and blie, blie

Question 23

Siderblastic anemia

Answer 23

ring siderblasts in bone marrow (excessive Fe accumulation)

Impaired heme biosyn

Microcytic and hypochromic

Mito metabolism problems

Nucleated RBC

Question 24

hereditary sidero anemia

Answer 24

X-linked-erythroid spec=ALAS2

mtDNA mistake

Question 25

Aquired

Answer 25

Myedisplasia-mtDNA pt muts Drugs-Isoniazid/ethanol Toxins-lead Nutritional-pyrixidoxine defeciency

Question 26

Trx Pb poisoning

Answer 26

chelators

Question 27

Pb poisioning presentation

Answer 27

lethary, ab discomfort, anemia, gingival and long bone pb line, headache convulsions, coma, renal failure

Question 28

Diagnosis of Pb poisoning

Answer 28

ALA in urine ZPP in blood (goes into protophyrin 9 instead of Fe) Basophilic stippling in peripheral smear

Question 29

Acute porphyria vs nonacute

Answer 29

acute-ALA/PBG up, decrease in heme-neuropsych signs and symtoms Nonacute-accumulation of porphyrinogens in skin and tissue, spontaneous oxidation of porhyringens to porphyrins, photosenstivity

Question 30

acute and non acute porphyria sims

Answer 30

mostly auto dom both have genetic and non genetic factors (some are auto rec tho)

Question 31

AIP

Answer 31

PBGD defieciency

Question 32

Symptoms of AIP

Answer 32

Accumulation of ALA and PBG -neurotoxic levels NO SKIN LESIONS Gi disorder, psych disorders, all at risk for liver cancer Attack of AIP after 4M 2nd most common

Question 33

PBG in urine

Answer 33

Brown/Red

Question 34

AIP trx

Answer 34

Avoid 4M, glucose loading, admin hemin/hematin, stop p450 syn DECREASE ALA SYN

Question 35

PTC

Answer 35

UROD Problem Acquired or autu dominant (familial PCT)

Question 36

Factors affect PTC onset and symptoms

Answer 36

4th/5th decade onset alc, fe overload, sunligh, HIV/HEP C/B bullae, hypertrichosis, heliotrope, sclerodermoid plaque, dark urine, milia

Question 37

milia, bullae, hypertrichosis, helitrope

Answer 37

milic-small white bumps in skin hypertrichosis-har growing in weird splot bullate-fluid filled blister (large) heliprope-purple-red face skin

Question 38

What causes bad things in PTC

Answer 38

ring intermediates getting hit by sunlight and become reactive O2 species

Question 39

PTC diagnosis

Answer 39

Uro to copro 3:1 instead or 5:1 more 8-7 carboxyl porphyrin fractions UROD in blood analysis

Question 40

Trx for PTC

Answer 40

No env exosures Sunscreen Fe Chelator Bleeding (reduces Fe stores and heme syn up)

Question 41

EPP

Answer 41

Autodom Ferrochelatase mutation Early childhood presentation SEVERE PHOTOSENSTIVITY Chornic liver diease