This document summarizes the biosynthesis and degradation of porphyrin and heme. It discusses how glycine and succinyl CoA are condensed to form δ-aminolevulinate, the starting material for porphyrin synthesis. Four molecules of porphobilinogen then condense to form the porphyrin ring. A series of reactions incorporates iron to form heme. Heme is degraded through heme oxygenase to form biliverdin and bilirubin, which is transported to the liver bound to albumin.

1. Submitted by
T.Soundarya
I- M.Sc biochemistry
P19BC004
BIOSYNTHESIS AND DEGRADATION OF PORPHYRIN
AND HEME

2. SYNOPSIS :
 Introduction
 Biomedical importance
 Porphyrin
 Biosynthesis of heme
 formation of heme
 Degradation heme
 Conclusion
 References

3. INTRODUCTION :
 The heme speaks about:
“ I am the red of blood, responsible for respiration ;

5. Types of porphyrin :

6. • Heme isthe most important porphyrin
containing compound.
• It isprimarily synthesized in the liver &the
erythrocyte- producing cells of bone marrow
(erythroidc ells).
• Heme synthesis also occursto some extent in other
tissues.
• Mature erythrocytes lacking mitochondria are a
notable exception.

7. Formation of δ-aminolevulinate
• Glycine, a non-essential amino acid &succinyl CoA,
an intermediate in the citric acid cycle, are the
starting materials for porphyrin synthesis.
• Glycine combines with succinyl CoAto form
δ – aminolevulinate (ALA).
• Catalysed by a PLPdependent δ –
aminolevulinate synthase occursin the
mitochondria.
• It isa rate-controlling step in porphyrin synthesis

8. Synthesis of porphobilinogen
• Two molecules of δ -aminolevulinate condense to
form
 porphobilinogen (PBG) in the cytosol.
• Catalysed by a Zn-containing enzyme ALA
dehydratase.
• It issensitive to inhibition by heavy metals suchas
lead.

9. Formation of porphyrinring
• Porphyrin synthesis occursby condensation of four molecules
of porphobilinogen (PBG).
• Thefour pyrrole rings in porphyrin are interconnected by
methylene (-CH2)bridges derived from α- carbon of
glycine.
• Theinteraction of two enzymes-namely uroporphyrinogen I
 synthase &uroporphyrinogen lll cosynthase-results in
condensation of porphobilinogen followed by ring closure
& isomerization to produce uroporphyrinogen lll.

10. Conversion of uroporphyrinogen lll to
protoporphyrin lX
• Uroporphyrinogen decarboxylase decarboxylates
all the four acetate (A) side chains to form methyl
groups (M), to produce coproporphyrinogen.
• Coproporphyrinogen oxidase converts (oxidative
decarboxylation) two of the propionate side
chains (P) to vinyl groups (V) &results in the
formation of protoporphyrinogen

11. • Protoporphyrinogen oxidase oxidizes methylene
 groups (-CH2-) interconnecting pyrrole rings to
methenyl groups (=CH-).
• Thisleads to the synthesis of protoporphyrin lX.

12. Synthesisof heme from protoporphyrin
lX
• The incorporation of ferrous iron (Fe2+) into
protoporphyrin IX iscatalysed by the enzyme
ferrochelatase or heme synthetase.
• Thisenzyme can be inhibited by lead.

14. Effect of drugs on ALAsynthase
activity
• The activity of ALAsynthase ismarkedly increased by
the administration of a large number of drugs e.g.
phenobarbital, insecticides, carcinogens etc.
• These compounds are mostly metabolized by a
heme containing protein, cytochrome P450
• On administration of drugs, cellular levels of heme are
depleted due to its increased incorporation into
cytochrome P450.

15. Heme oxygenase
A complex microsomal enzyme, heme oxygenase
utilizes NADPH &O2 and cleaves the methenyl
bridges between the two pyrrole rings (A and B)
to form biliverdin.
Simultaneously, ferrous iron (Fe2+) isoxidized to
ferric form (Fe3+) & released.

16.  Biliverdin's methenyl bridges (between
the pyrrole rings Cand D) are reduced
to methylene group to form bilirubin
yellow pigment).
 Catalysed by an NADPH dependent
soluble enzyme, biliverdin reductase

18. Transport of bilirubin to liver
 Bilirubin is lipophilic &therefore insoluble in
aqueous solution.
 Bilirubin is transported in the plasma in a
bound (non-covalently) form to albumin.
 Albumin has two binding sites for bilirubin-a
high affinity site &a low affinitysite.

19.  Text book of Biochemistry – U Satyanarayana
 Text book of Biochemistry – DM Vasudevan
Text book of Biochemistry – MN Chatterjea
 Text book of Biochemistry – harper illustrated