Uroporphyrinogen I is an isomer of

uroporphyrinogen III Uroporphyrinogen III is a tetrapyrrole, the first macrocycle, macrocyclic intermediate in the biosynthesis of heme, chlorophyll, vitamin B12, and siroheme. It is a colorless compound, like other porphyrinogens. Structure The molecular structure of ...

, a

metabolic intermediate Metabolic intermediates are compounds produced during the conversion of substrates (starting molecules) into final products in biochemical reactions within cells. Although these intermediates are of relatively minor direct importance to cell ...

in the

biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...

heme Heme (American English), or haem (Commonwealth English, both pronounced /Help:IPA/English, hi:m/ ), is a ring-shaped iron-containing molecule that commonly serves as a Ligand (biochemistry), ligand of various proteins, more notably as a Prostheti ...

. A type of

porphyria Porphyria ( or ) is a group of disorders in which substances called porphyrins build up in the body, adversely affecting the skin or nervous system. The types that affect the nervous system are also known as Porphyria#Acute porphyrias, acute p ...

is caused by production of uroporphyrinogen I instead of III.

Biosynthesis and metabolism

In living organisms, uroporphyrinogen I occurs as a side branch of the main

porphyrin synthesis Porphyrins ( ) are heterocyclic, macrocyclic, organic compounds, composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (). In vertebrates, an essential member of the porphyrin group is heme, wh ...

pathway. In the normal pathway, the linear tetrapyrrole precursor

preuroporphyrinogen Hydroxymethylbilane, also known as preuroporphyrinogen, is an organic compound that occurs in living organisms during the synthesis of porphyrins, a group of critical substances that include haemoglobin, myoglobin, and chlorophyll. The name is oft ...

(a substituted hydroxymethylbilane) is converted by the

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

uroporphyrinogen-III cosynthase into the cyclic

; which is then converted to

coproporphyrinogen III Coproporphyrinogen III is a metabolic intermediate in the biosynthesis of many compounds that are critical for living organisms, such as hemoglobin and chlorophyll. It is a colorless solid. The compound is a porphyrinogen, a class of compounds c ...

on the way to

porphyrin Porphyrins ( ) are heterocyclic, macrocyclic, organic compounds, composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (). In vertebrates, an essential member of the porphyrin group is heme, w ...

s like

. Uroporphyrinogen I is instead produced spontaneously from preuroporphyrinogen when the enzyme is not present. Uroporphyrinogen I synthesis from preuroporphyrinogen

Uroporphyrinogen I synthesis from preuroporphyrinogen

The difference between the I and III forms is the arrangement of the four carboxyethyl groups (

propionic acid Propionic acid (, from the Greek language, Greek words πρῶτος : ''prōtos'', meaning "first", and πίων : ''píōn'', meaning "fat"; also known as propanoic acid) is a naturally occurring carboxylic acid with chemical formula . It is a ...

, "P") and the four carboxymethyl groups (

acetic acid Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main compone ...

, "A"). The non-enzymatic conversion to uroporphyrinogen I results in the sequence AP-AP-AP-AP, whereas the enzymatic conversion into uroporphyrinogen III leads to reversal of one AP-group and hence an AP-AP-AP-PA arrangement. If synthesized, uroporphyrinogen I is then converted into coproporphyrinogen I by the same enzyme ( uroporphyrinogen decarboxylase) that acts on the III form; but that product, which is

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are toxic metals, toxic chemicals, microbe neurotoxins, radiation particles and even specific neurotransmitters when the system is out of balance. Also some types of dr ...

, then accumulates causing the

pathology Pathology is the study of disease. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in the context of modern medical treatme ...

congenital erythropoietic porphyria A birth defect is an abnormal condition that is present at birth, regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can range from mild to severe. Birth ...

References

{{Tetrapyrroles Tetrapyrroles