PORPHYRIN AND HEME

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

PORPHYRINS
HC

CH

HC

CH

N
H

Pyrrole ring

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

Heme

Protoporphyrin III
prefix or suffi x
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

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

4
5

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

protoheme

O2

protohemin (or hemin) contains Fe3+

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