L4_Heme Metabolism

Question 1

How many pyroles in a porphyrin ring?

Answer 1

4

Question 2

How many members in a pyrole ring?

Answer 2

5

Question 3

name the order of the substituent groups on heme?

Answer 3

MVMVMPPM
m=methyl
p=propionate
V=vinyl

Question 4

what isomer of protoporphyrin is in heme?

Answer 4

protoporphyirn IX

Question 5

What is heme called if it has Fe3+

Answer 5

hemin

Question 6

Describe the differences between Heme A, B, and C

Answer 6

Heme A contains a modification to the number 2 vinyl group
Heme B is the standard
Heme C is covalently bound to cysteine residues of proteins through the two vinyl groups

Question 7

What is different about the axial ligands of Heme C when compared to A and B

Answer 7

It uses a methionine group as one of its axial ligands

Question 8

What are the two basic, simple precursors of Heme?

Answer 8

Glycine and Succinyl Coenzyme A

Question 9

How many ALA molecules to make a pyrole?

Answer 9

2

Question 10

How many glycine and Succinyl CoA to make an ALA?

Answer 10

1

Question 11

How many ALA per heme?

Answer 11

8

Question 12

How many glycine and Succinyl CoA per Heme?

Answer 12

8 each

Question 13

What does ALA stand for?

Answer 13

Aminolevulinate

Question 14

Where are most metabolic pathways normally regulated?

Answer 14

At the first step

Question 15

how many ALAs per porphobilinogen?

Answer 15

2

Question 16

What is the enzyme that converts 2 ALA to porphobilinogen?

Answer 16

ALA dehydrase

Question 17

Where does ALA dehydrase work?

Answer 17

cytosol

Question 18

What can inhibit ALA dehydrase?

Answer 18

lead, binds where a normal Zn cofactor normally binds

Question 19

What 2 enzymes does lead inhibit, what builds up in each of these situations?

Answer 19

it inhibits ALA dehydrase and results in a build up of ALA which resembles GABA and fucks up brain development. It also inhibits ferrochelatase which causes coproporphyrinogen III to build up in the serum.

Question 20

How many porphobiligens per uroporphyrinogen?

Answer 20

4

Question 21

Describe how porphobiligen gets to uroporphyrinogen III, where does this take place?

Answer 21

4 porphobiligens are condensed and cyclized into the tetrapyrole ring uroporphyrinogen I by urophorphyrinogen synthase. Uroporphyrinogen I is them isomerized to uroporphyrinogen III by uroporphyrinogen III cosynthase. This all happens in the cytosol.

Question 22

Describe how uroporphyrinogen III is converted into Protoporphyrin IX

Answer 22

Uroporphyrinogen decarboxyalse catalyses the decarboxylation of four acetyl side chains to methyl groups to make coproporphyrinogen III. Coproporphyrinogen oxidase decarboxylates the two propionyl side chains to vinyl groups to form protoporphyrinogen IX. Protoporphyrinogen oxidase removes six H atoms to form Protoporphyrin IX

Question 23

Where are Uroporphyrinogen decarboxylase, coproporphyrinogen oxidase and protoporphyrinogen oxidase located?

Answer 23

Uro is in the cytosol, the other 2 are in the mitochondrial matrix

Question 24

how is Protoheme IX made?

Answer 24

ferrochelatase inserts Fe 2+ into protoporphyrin IX in the mitochondria.

Question 25

Where does ALA synthase work?

Answer 25

In the mitochondria

Question 26

Where are the two main sites of heme biosynthesis?

Answer 26

The liver and erythroid cells (85%)

Question 27

What is heme used for in the liver?

Answer 27

Cytochrome P450s important oxidative enzymes involved in detoxification.

Question 28

Describe heme synthesis in erythroid cells?

Answer 28

It happens mainly once in their life and heme is a positive feedback process.

Question 29

How does the liver tend to regulate Heme synthesis? inhibited and induced?

Answer 29

By targeting ALA synthase. This step is feedback inhibited by heme (repression of mRNA synthesis, inhibition of translation of ALA mRNA, inhibition of import into the mitochondira, direct inhibition of the enzyme) heme synthesis is induce by toxins or substances that also induce cytochrome P450 (TYLENOL-acetaminophen)

Question 30

Why shouldnt you take Tylenol for a hangover?

Answer 30

becasue alcohol induce P450 synthesis. Acetominophen is broken down by P450 into hepatotoxic stuff.

Question 31

What are porpyrias? What is their inheritance pattern?

Answer 31

genetic deficiencies in heme metabolism. Enzymes are usually partially defective because fully defective would be lethal. (dominant inheritance due to haploid insufficiency)

Question 32

What is a major difference between hepatic porphyrias and erythopoietic porphyrias?

Answer 32

Hepatic are specific for the liver and attacks are generally induced, meaning under normal circumstances they work sufficiently. Erythropoietic are are chronic conditions.

Question 33

describe the defect and symptoms of Congenital erythropoietic porphyria. What builds up?

Answer 33

deficiency in Uroporphyrinogen III cosynthase leads to build up of Uro I and copro I. this causes anemia and the skin is photosensitive such that it ulcerates and forms disfiguring scars, red urine, teeth turn reddish brown and increased hair growth

Question 34

Describe the defect and symptoms of Protoporphyria and compare its severity to congenital erythopoietic porphyria. What build up?

Answer 34

Defect in ferrochelatase causes build up of copro III and symptoms similar to, but less severe than CEP

Question 35

Describe the defect and symptoms of acute intermittent porphyria. What builds up?

Answer 35

affects the liver. and is the most common porphyria. caused by partial deficiency of porphobilinogen deanimase (uroporphyrinogen synthase) under normal conditions you are fine, but when liver is stressed ALA and porphobilinogen build up. Abdominal pain, vomiting, diarrhea, neuro, red urine

Question 36

Describe the defects and symptoms of Porphyria cutanea tarda. What builds up? how can you treat it?

Answer 36

deficiency in uroporphyrinogen decarboxylase (sporadic or autosomal dominant but may be multifactorial) Asymptomatic until liver disorder is imposed, photosensitivity, can be casued by behavioral factors or environmental. Uro III builds up. depletion of the bodies iron stores often leads to remission of symptoms.

Question 37

What is porphyrin? what is porphyrinogen?

Answer 37

Porphyrin- oxidized tetrapyrrole | porphyrinogen - reduced tetrapyrrole

Question 38

What is a hallmark sign for sensitivity to the sun

Answer 38

Erythropoietic porphyrias