Heme Synthesis and Degradation, and the Porphyrias

Question 1

Hemoproteins

Answer 1

Need essential heme cofactor to function

Question 2

Cytochrome P450

Answer 2

Important hemoprotein involved in ET and metabolism

Question 3

Heme types

Answer 3

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

Question 4

Heme synthesis starting mateirals

Answer 4

Succinyl-CoA and Glycine

Question 5

Heme synthesis locations

Answer 5

Starts in mito, moves to cyto, back into mito

Question 6

1st 3 steps of heme synthesis

Answer 6

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

Question 7

Final 5 steps of heme synthessi

Answer 7

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

Question 8

Sites of heme synthesis

Answer 8

Almost all cells
85% in erythroid
14 in hepatocytes

Question 9

In hepatocytes,

Answer 9

Heme is required for insertion into cytochromes

Question 10

ALA-synthase regulation

Answer 10

Hemin (3+ Fe) inhibits along with glucose

Barbituations stimulate

Question 11

In erythroid cells, heme syntehsis controlled by

Answer 11

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

Heme must last for 120 days

Question 12

Porphyrias

Answer 12

Def in heme synthesis

Question 13

Lead poisoning

Answer 13

Inhibits ALA dehydratase and ferrochelatase

Question 14

Acute intermittent porphyria major symptoms and products

Answer 14

Neurovisceral

Urinary ALA and PBG

Question 15

Porphyria cutanea symtpoms and products

Answer 15

Photosnesitivty

Urinary 7-carboxylate porphyrin, fecal isocoproporphyrin

Question 16

Acute intermittent porphyria mutation, tx, symptoms,

Answer 16

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

Use glucose/hemin to tx

Question 17

Prophyria cutane tarda mutation and symptoms and tx

Answer 17

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

Question 18

Barbituates and porphyrias

Answer 18

NEVER prescribe because activates ALA_synthase

Question 19

Heme degradation steps

Answer 19

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

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

Question 20

Biliverdin and bilirubin colors

Answer 20

Verdin - blue green
Rubin - red yellow

Change from biliverdin to bilirubin responsible for bruise

Question 21

Bilirubin modified by

Answer 21

UGT1A in heptaocytes to increase solubility and aid in excretion

Question 22

Bilirubin transport

Answer 22

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

Question 23

Hyperbilirubinemia

Answer 23

Jaundice

Yellow coloring of skin and eyes

Question 24

Neonatal jaundice

Answer 24

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