Protoporphyrin IX is an
organic compound, classified as a
porphyrin, that plays an important role in living organisms as a precursor to other critical compounds like
heme (
hemoglobin) and
chlorophyll. It is a deeply colored solid that is not soluble in water. The name is often abbreviated as PPIX.
Protoporphyrin IX contains a
porphine core, a
tetrapyrrolemacrocycle with a marked
aromatic character. Protoporphyrin IX is essentially planar, except for the N-H bonds that are bent out of the plane of the rings, in opposite (trans) directions.[2]
Nomenclature
The general term protoporphyrin refers to porphine derivatives that have the outer
hydrogen atoms in the four
pyrrole rings replaced by other functional groups. The prefix proto often means 'first' in science nomenclature (such as
carbon protoxide), hence
Hans Fischer is thought to have coined the name protoporphyrin as the first class of porphyrins.[3] Fischer described iron-deprived heme becoming the "proto-" porphyrin, particularly in reference to Hugo Kammerer's porphyrin.[4][5] In modern times, 'proto-' specifies a porphyrin species bearing methyl, vinyl, and carboxyethyl/propionate side groups.[6]
Fischer also generated the
Roman numeral naming system which includes 15 protoporphyrin analogs, the naming system is not systematic however.[7] An alternative name for heme is iron protoporphyrin IX (iron PPIX). PPIX contains four
methyl groups −CH3 (M), two
vinyl groups−CH=CH2 (V), and two
propionic acid groups −CH2−CH2−COOH (P). The suffix "IX" indicates that these chains occur in the circular order MV-MV-MP-PM around the outer cycle at the following respective positions: c2,c3-c7,c8-c12,c13-c17,c18.[7]
The
methine bridges of PPIX are named alpha (c5), beta (c10), gamma (c15), and delta (c20). In the context of heme, metabolic biotransformation by
heme oxygenase results in the selective opening of the alpha-methine bridge to form
biliverdin/
bilirubin. In this case, the resulting
bilin carries the suffix IXα which indicates the parent molecule was protoporphyrin IX cleaved at the alpha position. Non-enzymatic oxidation may result in the ring opening at other bridge positions.[8] The use of Greek letters in this context originates from the pioneering work of
Georg Barkan in 1932.[9]
Properties
When UV light is shone on the compound, it
fluoresces with a bright red color.
It Is also the component in egg shells that give them their characteristic brown color.[10]
Natural occurrence
The compound is encountered in nature in the form of
complexes where the two inner hydrogen atoms are replaced by a
divalent metal
cation. When complexed with an
iron(II) (ferrous) cation Fe2+, the molecule is called
heme. Hemes are
prosthetic groups in some important proteins. These heme-containing proteins include hemoglobin,
myoglobin, and
cytochrome c. Complexes can also be formed with other metal ions, such as
zinc.[11]
Protoporphyrin IX is an important precursor to biologically essential prosthetic groups such as heme, cytochrome c, and chlorophylls. As a result, a number of organisms are able to synthesize this tetrapyrrole from basic precursors such as
glycine and
succinyl-CoA, or
glutamic acid. Despite the wide range of organisms that synthesize protoporphyrin IX, the process is largely conserved from bacteria to mammals with a few distinct exceptions in higher plants.[12][13][14]
In the biosynthesis of those molecules, the metal cation is inserted into protoporphyrin IX by enzymes called
chelatases. For example,
ferrochelatase converts the compound into
heme B (i.e. Fe-protoporphyrin IX or protoheme IX). In chlorophyll biosynthesis, the enzyme
magnesium chelatase converts it into
Mg-protoporphyrin IX.
Described metalloprotoporphyrin IX derivatives
Protoporphyrin IX reacts with iron salts in air to give the complex FeCl(PPIX).[15] Heme coordinated with chlorine is known as hemin. Many metals other than Fe form
Heme-like complexes when coordinated to PPIX. Of particular interest are
cobalt derivatives because they also function as oxygen carriers.[16] Other metals—nickel, tin, chromium—have been investigated for their therapeutic value.[17]
Palepron is the disodium salt of protoporphyrin IX.[18]
^Winslow S. Caughey; James A. Ibers (1977). "Crystal and Molecular Structure of the Free Base Porphyrin, Protoporphyrin IX Dimethyl Ester". J. Am. Chem. Soc. 99 (20): 6639–6645.
doi:
10.1021/ja00462a027.
PMID19518.