Heme Synthesis and Degradation, and the Porphyrias Flashcards Preview

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Flashcards in Heme Synthesis and Degradation, and the Porphyrias Deck (24)
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1

Hemoproteins

Need essential heme cofactor to function

2

Cytochrome P450

Important hemoprotein involved in ET and metabolism

3

Heme types

A - chain
B - kind in hemoglobin
C - attached to protein

4

Heme synthesis starting mateirals

Succinyl-CoA and Glycine

5

Heme synthesis locations

Starts in mito, moves to cyto, back into mito

6

1st 3 steps of heme synthesis

ALA-synthase takes glycine and succinyl-CoA to 5-aminolevulinic acid

ALA-dehydratase takes 5-animolevulinic acid to porphobilinogen

PBG-deaminase takes porphobilinogen to hydroxymethylbilane

7

Final 5 steps of heme synthessi

UPG 3 synthase takes hydroxymethylbilane to urophorphyrinogen 3

UPG 3 decarboxylase takes uroporphyrinogen 3 to coproporphyrinogen 3

CPG oxidase takes coproporphyrinogen 3 to protoporphyrinogen 9

PPG-oxidase takes protoporphyrinogen 9 to protoporphyrin 9

Ferrochelatase uses iron to take protoporphyrin 9 to heme B

8

Sites of heme synthesis

Almost all cells
85% in erythroid
14 in hepatocytes

9

In hepatocytes,

Heme is required for insertion into cytochromes

10

ALA-synthase regulation

Hemin (3+ Fe) inhibits along with glucose

Barbituations stimulate

11

In erythroid cells, heme syntehsis controlled by

Heme differentiation...if not enough iron, then ferrochelatase step cannot work

Heme must last for 120 days

12

Porphyrias

Def in heme synthesis

13

Lead poisoning

Inhibits ALA dehydratase and ferrochelatase

14

Acute intermittent porphyria major symptoms and products

Neurovisceral

Urinary ALA and PBG

15

Porphyria cutanea symtpoms and products

Photosnesitivty

Urinary 7-carboxylate porphyrin, fecal isocoproporphyrin

16

Acute intermittent porphyria mutation, tx, symptoms,

PBG deaminase mutation
Ab pain, port wine urine, polyneuropathy, psych issues
Exacerbatedb y alcohol and some drugs

Use glucose/hemin to tx

17

Prophyria cutane tarda mutation and symptoms and tx

Most sporadic (some auto dom)
Def in UPG 3 decarboxylase

Blistering and photosensitivity

Reduce exposure to sun, alcohol, anti-malarial drugs...remove iron from system

18

Barbituates and porphyrias

NEVER prescribe because activates ALA_synthase

19

Heme degradation steps

HMOX - Takes heme to biliverdin 9 (uses NADP and O2)

biliverdin reductase - takes biliverdin 9 to biliubin 9...uses NADPH

20

Biliverdin and bilirubin colors

Verdin - blue green
Rubin - red yellow

Change from biliverdin to bilirubin responsible for bruise

21

Bilirubin modified by

UGT1A in heptaocytes to increase solubility and aid in excretion

22

Bilirubin transport

In macrophage...breakdown to bilirubin

Transport to hepatocyte...conjugate and moved to intestine

In intestine, converted to urobilinogen...some of this converted to stercobilin...some moves to kidney

In kidney, convered to urobilin and excrete

23

Hyperbilirubinemia

Jaundice
Yellow coloring of skin and eyes

24

Neonatal jaundice

Due to immature UGT enzymes plus high turnover rate of RBC s to replace HbF with HbA

Apparent after 24 houts...resolved after 1-2 weeks

Phototherapy isomerizes bilirubin to more soluble form