Cytochrome P450 oxidoreductase deficiency (PORD) is a rare disease and

inborn error of metabolism Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of enzyme activities. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances (substrat ...

caused by deficiency of cytochrome P450 oxidoreductase (POR). POR is a 2- flavin

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that is responsible for the

transfer Transfer may refer to: Arts and media * ''Transfer'' (2010 film), a German science-fiction movie directed by Damir Lukacevic and starring Zana Marjanović * ''Transfer'' (1966 film), a short film * ''Transfer'' (journal), in management studies * ...

electron The electron (, or in nuclear reactions) is a subatomic particle with a negative one elementary charge, elementary electric charge. It is a fundamental particle that comprises the ordinary matter that makes up the universe, along with up qua ...

s from

NADPH Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require N ...

to all 50

microsomal In cell biology, microsomes are heterogeneous vesicle-like artifacts (~20-200 nm diameter) re-formed from pieces of the endoplasmic reticulum (ER) when eukaryotic cells are broken-up in the laboratory; microsomes are not present in healthy, l ...

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

(CYP450)

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 ...

s. This includes the

steroidogenic enzyme __NOTOC__ Steroidogenic enzymes are enzymes that are involved in steroidogenesis and steroid biosynthesis. They are responsible for the biosynthesis of the steroid hormones, including sex steroids (androgens, estrogens, and progestogens) and co ...

CYP17A1 Cytochrome P450 17A1 (steroid 17α-monooxygenase, 17α-hydroxylase, 17-alpha-hydroxylase, 17,20-lyase, 17,20-desmolase) is an enzyme of the hydroxylase type that in humans is encoded by the ''CYP17A1'' gene on chromosome 10. It is ubiquitously e ...

(17α-hydroxylase/17,20-lyase), CYP19A1 (aromatase), and

CYP21A2 Steroid 21-hydroxylase is a protein that in humans is encoded by the ''CYP21A2'' gene. The protein is an enzyme that Hydroxylation, hydroxylates steroids at the C21 position on the molecule. Naming conventions for enzymes are based on the subst ...

(21-hydroxylase);

CYP26B1 Cytochrome P450 26B1 is a protein that in humans is encoded by the ''CYP26B1'' gene. This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved ...

(metabolizes

retinoic acid Retinoic acid (simplified nomenclature for all-''trans''-retinoic acid) is a metabolite of vitamin A1 (all-''trans''-retinol) that is required for embryonic development, male fertility, regulation of bone growth and immune function. All-''trans ...

); and the

hepatic The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

- metabolizing CYP450 enzymes (e.g.,

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

), among many other CYP450 enzymes. Virilization of female infants in PORD may also be caused by alternative biosynthesis of

5α-dihydrotestosterone Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone primarily involved in the growth and repair of the prostate and the penis, as well as the production of ...

via the so-called "

androgen backdoor pathway The androgen backdoor pathway (the backdoor pathway of androgen biosynthesis) is a metabolic route in which androgens are produced from 21-carbon () steroids bypassing testosterone and androstenedione as intermediates. This process starts wi ...

". The ABS component of severe forms of PORD is probably caused by CYP26B1 deficiency, which results in retinoic acid excess and

defect Defect or defects may refer to: Related to failure * Angular defect, in geometry * Birth defect, an abnormal condition present at birth * Crystallographic defect, in the crystal lattice of solid materials * Latent defect, in the law of the sale o ...

s during

skeletal A skeleton is the structural frame that supports the body of most animals. There are several types of skeletons, including the exoskeleton, which is a rigid outer shell that holds up an organism's shape; the endoskeleton, a rigid internal fram ...

embryogenesis An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male ...

. All forms of PORD in humans are likely partial, as POR

knockout A knockout (abbreviated to KO or K.O.) is a fight-ending, winning criterion in several full-contact combat sports, such as boxing, kickboxing, Muay Thai, mixed martial arts, karate, some forms of taekwondo and other sports involving striking, ...

in mice results in death during

prenatal development Prenatal development () involves the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal de ...

Symptoms and signs

Symptom Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...

s of severe forms of PORD include

ambiguous genitalia Intersex people are those born with any of several Sexual characteristics, sex characteristics, including chromosome patterns, gonads, or sex organ, genitals that, according to the Office of the United Nations High Commissioner for Human ...

in males and females,

congenital adrenal hyperplasia Congenital adrenal hyperplasia (CAH) is a group of Genetic disorder#Autosomal recessive, autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the Biosy ...

, cortisol deficiency, and Antley–Bixler skeletal malformation syndrome (ABS), while symptoms of mild forms include

polycystic ovary syndrome Polycystic ovary syndrome, or polycystic ovarian syndrome, (PCOS) is the most common endocrine disorder in women of reproductive age. The name is a misnomer, as not all women with this condition develop cysts on their ovaries. The name origin ...

in women and

hypogonadism Hypogonadism means diminished functional activity of the human gonad, gonads—the testicles or the ovary, ovaries—that may result in diminished biosynthesis, production of sex hormones. Low androgen (e.g., testosterone) levels are referred t ...

in men. Maternal

virilization Virilization or masculinization is the biological development of adult male characteristics in young males or females. Most of the changes of virilization are produced by androgens. Virilization is a medical term commonly used in three medical a ...

also occurs in severe forms, due to

aromatase deficiency Aromatase deficiency is a rare condition characterized by extremely low levels or complete absence of the enzyme aromatase activity in the body. It is an autosomal recessive disease resulting from various mutations of gene CYP19 (P450arom) which ...

in the

placenta The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...

References

{{Defects of steroid metabolism Endocrine gonad disorders Rare diseases Intersex variations

Symptoms and signs

See also

References