PORPHYRIN AND HEME METABOLISM

Porphyrins metal and protein Hemoproteins

Heme Hemoglobin
Iron Globin chains Protoporphyrin III (IX)

PORPHYRINS
HC HC N H CH CH
NOMENCLATURE Types of substituents Symmetry I or III Oxidation between rings
Methylene -CH2 Methene -CH=

Pyrrolering

Heme

Protoporphyrin III
prefix or suffix urocoproproto-porphyrinogen -porphyrin ring substituents acetate, propionate methyl, propionate methyl, propionate, vinyl --between rings --methylene methene

Reactions for Protoporphyrin IX

Step 1 Synthesis of -amino levulinic acid

Mitochondrial location Rate limiting Pyridoxal phosphate (decarboxylase) Regulation of enzyme levels by iron and protohemin

Step 2 Synthesis of porphobilinogen

Also called porphobilinogen synthase Zinc-dependent Site of lead toxicity

Further Reactions
Step 3 Tetrapyrrole formation
synthesis of hydroxymethylbilane synthesis of uroporphyrinogen III uro to copro copro to proto porphyrinogen to porphyrin insertion of ferrous iron site of lead toxicity

Step 4 Conversion to protoporphyrin III

Step 5 Protoheme synthesis

1 2

3 4

4 5

Heme Proteins
Protoheme (or heme) + globin ~ hemoglobin Protohemin formation -- formation of superoxide
O2 O2

protohemeprotohemin(orhemin)containsFe 3+

Variations in heme Fe ligands 4, 5, or 6 Ferrous or Ferric Protoporphyrin III attachment to protein

Heme b

Heme c

Heme a

Iron-IRE

Porphyrias
Treatment Hematin (hemin hydroxide)

Heme Degradation Fig. 44.7 Page 839

Reactions Fig. 44.8 Page 840

Heme oxygenase Biliverdin reductase Serum albumin GSH S-transferase Bilirubin UDP-glucuronyl transferase

Spleen Macrophages Blood Liver

Heme Degradation
Features Reactions Jaundice Blood Proteins
serum albumin haptoglobin hemopexin

hemolytic obstructive Neonate kernicterus liver disease Gilberts disease

Blood So Far
Plasma Erythrocyte
Hemoglobin
Globin chains Protoporphyrin III Iron

Iron Balance

IRON METABOLISM
Fig. 44.6 Page 838

Iron Absorption
Low but regulated Ferrous iron conversion needed Heme iron by separate pathway Reducing agents aid uptake-vitamin C Factors in breast milk facilitate uptake (lactoferrin)

Promoters and inhibitors of non-heme iron absorption

Promoters: Ascorbic acid Meat Citric Acid Some spices -carotene Alcohol Inhibitors: Phytic acid Polyphenols Tannins Calcium
Adapated from Paul Sharp Kings College UK