Porphyrin Metabolism Flashcards Preview

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Flashcards in Porphyrin Metabolism Deck (31):
1

The overall synthesis of heme requires what?

8 enzymes, pyridoxal phosphate, Mg2+, O2, and reducing substances

2

What are the byproducts of heme synthesis?

8 CoA, 14 CO2, 4 NH4

3

Where is heme synthesis located?

liver and erythropoietic tissue

4

Erythropoietic tissue forms heme for ____. Liver forms heme for incorporation into ____.

hemoglobin; cytochromes

5

The first step and the last three steps of heme synthesis are located where?

mitochondria; the rest are cytosolic

6

This is a mitochondrial enzyme coded for by nuclear genes, synthesized on cytosolic ribosomes, and transported into the mitochondria. It requires pyridoxal phosphate and Mg2+.

Delta-Aminolevulinic acid synthetase

7

This is a cytosolic enzyme. It allows two molecules of Aminolevulinic Acid (ALA) - formed by D-ALA syntehetase -to condense and form porphobilinogen. It is very sensitive to heavy metals (Pb).

Delta-Aminolevulinate dehydratase

8

This enzyme and coenzyme allow four molecules of porphobilinogen to condense head-to-tail, and become cyclized to form uroporphyrinogen.

Uroporphyrinogen I synthase I and Uroporphyrinogen III co-synthase (cytosolic)

9

In the absence of uroporphyrinogen III co-synthase, what occurs, in regards to production of uroporphyrinogen.

In the absence of Uroporphyrinogen III co-synthase, large amounts of uroporphyrinogen I are formed, while in the presence of Uroporphyrinogen III co-synthase, essentially only isomer III is produced.

10

Urophyrinogen decarboxylase (cytosolic) catalyzes the sequential decarboxylation of the four acetic acid side chains to methyl groups. What is this enzyme inhibited by?

iron salts

11

What is the role of corproporphyrinogen oxidase, what does it require, and where is it located?

converts the propionic acid groups of ring A and B to vinyl groups. It is specific for the type III isomer.

It requires O2 but no other cofactor or metal

It is located in the mitochondria

12

This enzyme is specific for protoporphyrinogen IX, requires O2, and reducing substances. The product, protoporphyrin IX is more water insoluble than previous precursors.

protoporphyringoen oxidase (mitochondrial)

13

This is the last enzyme found in heme synthesis. It inserts ferrous iron into protoporphyrin IX to yield heme. It is sensitive to heavy metals and is membrane associated.

Ferrochelatase (mitochondria)

14

What is the rate limiting step of heme synthesis in the liver?

D-ALA synthetase

15

Heme inhibits ALA synthetase at three points. What are they?

inhibition of the synthesis of the enzyme
inhibition of transport of the enzyme into the mitochondria
allosteric inhibitor of the enzyme activity

16

Repression of the synthesis of ALA synthetase is very efficient. Why?

the half-life is short, about 60 min

17

If a patient came in with ALA dehydrase deficiency due to a defect in ALA dehydrase, what would be the major symptom and biochemical finding?

symptom: neurological

biochemical finding: ALA urine

18

If a patient came in with acute intermittent porphyria and a defect in uroporphyrinogen I synthase, what would be the major symptom and biochemical finding?

symptom: neurological

biochemical finding: ALA, PBG urine

19

If a patient came in with congenital erythropoietic porphyria and a defect in uroporphyrinogen III cosynthase, what would be the major symptom and biochemical finding?

symptom: photosensitivity

biochemical finding: uroporphyrin urine, serum and feces

20

If a patient came in with porphyria cutanea tarda and a defect in uroporphyrinogen III decarboxylase, what would be the major symptom and biochemical finding?

symptom: photosensitivity

biochemical finding: uroporphyrin, urine and feces

21

hereditary coproporphyria/defect in coproporphyrinogen oxidase

symptom: photosensitivity and neurological

biochemical finding: ALA, PBG, coproporphyrin urine; coproporphyrin feces

22

variegate porphyria/defect in protoporphyrinogen oxidase

symptom: photosensitivity and neurological

biochemical finding: ALA, PBG, coproporphyrin urine; protoporphyrin feces

23

erythropoietic protoporphyria/ferrochelatase

symptoms: photosensitivity

biochemical finding: protoporphyrin erythrocytes and feces

24

Describe heme catabolism

1. Heme oxygenase of the reticuloendothelial cells - heme is released and converted to biliverdin
2. Biliverdin is converted to bilirubin by biliverdin reductase
3. Bilirubin is transported through the blood to the liver bound to albumin
4. Bilirubin is conjugated to form a diglucoronide in the liver
5. In the colon, bilirubin diglucoronide is converted to urobilinogen by intestinal bacteria

25

What is the only known source of endogenous CO?

Heme oxygenase

26

In the feces, urobilinogen becomes _____; In the urine, uroblinogen becomes ____

stercobilinogens; urobilins

27

Jaundice is yellowing of the skin due to increased plasma ____

bilirubin

28

Pre hepatic jaundice is due to production of bilirubin in excess of liver capacity to conjugate. Describe the status of serum, stools, and urine.

serum: increased total bilirubin with increased unconjugated bilirubin (direct)
stools: increased stercobilin excretion - normal color
urine: increased urobilin excretion

29

Hepatic jaundice is due to failure of liver to conjugate bilirubin. Describe the status of serum, stools, and urine

serum: increased total bilirubin with increased unconjugated bilirubin (indirect)
stools: decreased stercobilin - light color
urine: decreased urobilin excretion

30

Post hepatic jaundice is due to regurgitation of conjugated bilirubin into blood. Describe the status of serum, stools, and urine.

serum: increased total bilirubin with increased conjugated bilirubin (direct)
stools: decreased stercobilin - light color
urine: decreased urobilin - conjugated bilirubin is filtered by kidney and causes dark brown pigmentation of urine

31

Liver of neonate has limited capacity to conjugate bilirubin. True or false?

true