Biosynthesis of heme





                                       Biosynthesis of heme

•             Initial compound for synthesis is succinyl-CoA (intermediate of CC)

•             Source of nitrogen is glycin

•             reactions are located in mitochondria and cytoplasma

•             Regulation: ALA-synthase





                               Synthesis of d-aminolevulinate (ALA)



                         Why some drugs increase activity of ALA-synthase?

For biotransformation (hydroxylation) of xenobiotics is necessary cytochrom P-450

                                Condenzation to substituted pyrrol

                                  Condenzation of porfobilinogen

                                  Condenzation of porphobilinogen

                   Decarboxylation of four acetates – formation of methyl groups

                          Formation of vinyl groups from two propionates

                                  Formation of conjugated system

                                Heme is coloured chelate with Fe^2+

        Porhyrias are caused by partial deficiency of one of the heme synthesizing enzymes

Primary (genetic)

•             Defective enzyme of heme biosynthesis

•             Overproduction and accumulation of intermediates (ALA, PBG)

•             Porphyrinogens in skin - fotosensibility





Secondary

•             Inactivation of enzymes as a consequence of disease or poisoning

•             Similar symptoms

                                           Heme proteins

                        CO and bilirubin are formed by degradation of heme