Tetrapyrrole synthesis: heme syntheiss, porphyrias and catabolism

Question 1

What is heme structurally madde of?

Answer 1

Four pytole units forming a modified tetrapyrrole

Question 2

What metal ion does heme contain?

Answer 2

Fe2+ (ferrous iron)

Question 3

What are the main four functions of heme?

Answer 3

1 - Transport
2 - Sensor
3 - Electron transport
4 - Enzyme activity

Question 4

What metal does chlorophyll contain and what is its function?

Answer 4

Mg2+
Used in phhotosynthesis

Question 5

What is the central ion in vitamin B12?

Answer 5

Co2+ (cobalt)

Question 6

What enzymes require vitamin B12 as a cofactor?

Answer 6

Methionine synthase
Methylmalony-CoA mutase

Question 7

What is teh function of coenzyme F430, and what metal does it contain?

Answer 7

Mehtyl-CoM reductase
Contains Ni2+ (nickle)

Question 7

What structural feature allows tetraphyrolles to bind metal ions?

Answer 7

A large macrocylic ring

Question 7

What is siroheme used for, and what metal does it contain?

Answer 7

Sulfiite/nitrite reductase
Contains Fe2+

Question 8

What role do delocalised electrons in tetrapyrroles play?

Answer 8

Contribute to thier function (e.g., light capture in photosynthesis)

Question 8

Why is the metal ion important in tetrapyrroles?

Answer 8

It enables redox activity (e.g., Fe2+ <-> Fe3+)

Question 8

What are linear tetrapyrroles called?

Answer 8

Bilanes

Question 9

What are two human bile pigents that are bilanes?

Answer 9

Bilirubin
Biliverdin

Question 10

What are bilins used for in photosynthestic organisms?

Answer 10

Light harvesting (e.g., phycobilins in cyanobacteria and red algae)

Question 11

What are phycobilins often referred to?

Answer 11

Algal biles

Question 12

What is a modified tetrapyrrole?

Answer 12

A molecule composed of four pyrrole units used to bind metal ions in biological systems

Question 13

Why are modified tetrapyrroles important?

Answer 13

They play fundamental roles in metabolism, including 02 transport, electron transfer, and enzymatic reactions

Question 14

What do all meodified tetrapyrroles share strucurally?

Answer 14

A common macrocylic framework due to a branched biosynthetic pathway

Question 15

Which modified tetrapyrrole is synthesised by humans?

Answer 15

Heme

Question 16

What are the two amin stages of heme synthesis?

Answer 16

1 - Constrution of the macrocyle
2 - Modification of the macrocyle

Question 17

What is the goal of the macrocyle construction stage?

Answer 17

Formation of an unsymmetrical macrocylic ring

Question 18

What is the aim of the macrocyle modification?

Answer 18

To make the molecule more hydrophobic and aromatic

Question 19

What are the steps in macrocycle formation in heme synthesis?

Answer 19

1 - 2x 5-Aminoleculininc acid –>
2 - Porphobilinogen –>
3 - Hydroxymethylbilane –>
4 - Uroporphyrinogen III (first macrocyle intermediate)

Question 20

What are the steps in macrocycle modification in heme synthesis?

Answer 20

1 - Uroporphyrinogen III –>
2 - Coproporphyrinogen III –>
3 - Protoporphyrinogen IX –>
4 - Protoporphyrin IX –>
5 - Heme

Question 21

Who discovered the biosynthesis of ALA and how?

Answer 21

David Shemin used 15N-glycine tracinf and found heme has half-life of 50-55 days matching the lifespan of a red blood cell

Question 22

What is the significance of 5-Aminolevulinic acid (ALA)?

Answer 22

It is the precursos molecule in the biosyntheiss of heme

Question 23

How is Fe2+ made available for heme synthesis?

Answer 23

Through coordinated uptake, storage in ferritin, and delivery to ferrochelatase

Question 24

What enzyme inserts Fe2+ into protoporphyrin IX?

Answer 24

Ferrochelatase

Question 25

Why is iron delivery tightly regulated in heme synthesis?

Answer 25

To prevent toxic free iron accumulation and enzure synchrony with heme production

Question 26

Where does heme synthesis occur in the cell?

Answer 26

In the mitochondrion (compartmentalised process)