Heme biosynthesis involves 7 major steps to produce heme from its precursors. The major sites of heme biosynthesis are the liver and bone marrow. Disorders of heme synthesis can cause porphyrias, a group of inborn errors of metabolism associated with abnormalities in heme biosynthesis. Porphyrias are broadly classified into hepatic porphyrias, which affect the liver, and erythropoietic porphyrias, which affect red blood cell production.

1. HEME BIOSYNTHESIS AND
IT’S GENERAL OVERVIEW
PBL GROUP:A
4TH BATCH BMCTH (KU)

2. INTRODUCTION TO HEAMOGLOBIN
HAEMOGLOBIN
HEME + GLOBIN
HEME-PROSTHETIC GROUP (NON-PROTEINOUS PART)
GLOBIN-APOPROTIEN
HAEMOGLOBIN IS TETRAMERIC ALLOSTERIC PROTEIN MADE UP OF FOUR
POLYPEPTIDE CHAINS HAVING
TWO Α CHAIN -141 AMINO ACIDS
TWO Β CHAIN -146 AMINO ACIDS
BOND: NON-COVALENT STRUCTURES

4. OVERVIEW OF HEME
HEME IS COMPLEX OF PROTOPORPHYRIN IX HAVING FOUR
PYRROLE RING BRIDGE BY METHENYL GROUP WITH
CENTRALLY PLACED FERROUS IRON.
HAVING CO-ORDINATION NUMBER VI
IRON IS HELD IN THE CENTER OF THE HEME BY FOUR CO-
ORDINATED BONDS OF NITROGEN LINKAGE IN PORPHYRIN
RING.
ANOTHER TWO, ONE FOR HISTIDINE RESIDUE OF GLOBIN
MOLECULE AND WHEREAS THE OTHER POSITION IS AVAILABLE
TO BIND OXYGEN AND CARBONDIOXIDE AND SOMETIMES FOR

5. BIO SYNTHESIS OF HEME
IT CONSISTS OF 7 MAJOR STEPS WITH FORMATION OF
DIFFERENT INTERMEDIATE PRODUCT.
MAJOR SITES OF HEME BIOSYNTHESIS ARE THE IMMATURE
STEM CELLS OF LIVER
AND ALSO IN ERYTHROCYTE PRODUCING CELLS IN BONE
MARROW.

7. 1.ALA-DEHYDRATASE IS A ZINC CONTAINING ENZYME WHICH
GETS INHIBITED BY LEAD.
2.DRUGS LIKE BARBITURATES INDUCE HEME SYNTHESIS.
3.STEP CATALYZED BY FERROCHELATASE OR HEME SYNTHASE
IS ALSO INHIBITED BY LEAD
4.INH (ISONICOTINIC ACID) THAT DECREASES THE AVAILABILITY
OF PYRIDOXAL PHOSPHATE WHICH ULTIMATELY AFFECT THE
HEME SYNTHESIS.
5.HIGH CONCENTRATION OF CELLULAR GLUCOSE ALSO INHIBIT
ALA SYNTHASE.
6.ALA SYNTHASE IS RATE LIMITING ENZYME.

8. DISORDER OF HEME SYNTHESIS
1 PORPHYRIAS
 GROUP OF INBORN ERROR OF METABOLISM
ASSOCIATED WITH BIOSYNTHESIS OF HEME
CHARACTERIZED BY INCREASE IN PRODUCTION AND
EXCRETION OF PORPHYRINS
 PORPHYRIAS BROADLY CLASSIFIED AS
A. HEPATIC PORPHYRIAS
B. ERYTHROPOIETIC
PORPHYRIAS

9. Table-1: Major findings in disorders of porphyria