PORPHYRIN AND HEME

METABOLISM
Porphyrins metal and protein
Hemoproteins
Heme
Hemoglobin
Iron
Globin chains
Protoporphyrin III (IX)

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

prefix or suffix ring substituents between rings
uro- acetate, propionate --
copro- methyl, propionate --
proto- methyl, propionate, vinyl
-porphyrinogen -- methylene
-porphyrin -- methene

Reactions for
Protoporphyrin IX

Step 1
Synthesis of d-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
Step 4 Conversion to protoporphyrin III
uro to copro
copro to proto
porphyrinogen to porphyrin
Step 5 Protoheme synthesis
insertion of ferrous iron
site of lead toxicity

1
2
3
3
4
4
5
Heme Proteins
Protoheme (or heme) + globin ~ hemoglobin
O
2
O
2
-
protoheme protohemin (or hemin) contains Fe
3+
Protohemin formation -- formation of superoxide
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
hemolytic
obstructive
Neonate
kernicterus
liver disease
Gilberts disease
Blood Proteins
serum albumin
haptoglobin
hemopexin
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