L-gulonolactone oxidase
Encyclopedia
L-gulonolactone oxidase (EC
1.1.3.8) is an enzyme
that catalyzes the reaction
of D-glucuronolactone
(also known as L-gulono-1,4-lactone) with oxygen
to L-xylo-hex-3-gulonolactone and hydrogen peroxide
. It uses FAD
as a cofactor
. The L-xylo-hex-3-gulonolactone (2-keto-gulono-gamma-lactone) is able to spontaneously convert to hexuronic acid (ascorbic acid
), without enzymatic action.
8p21
that corresponds to an evolutionarily conserved segment on either porcine chromosome 4 (SSC4) or 14 (SSC14). GULO produces the precursor to ascorbic acid
, which spontaneously converts to the vitamin ("vitamin C
").
The loss of activity of the gene for L-gulonolactone oxidase (GULO) has occurred separately in the history of several species. The loss of this enzyme activity is responsible for the inability of guinea pig
s to enzymatically synthesize vitamin C, but this event happened independently of the loss in the haplorrhini
suborder of primates, including humans. The remains of this non-functional gene with many mutations is, however, still present in the genome of the guinea pigs and in humans. The function of GULO appears to have been lost several times, and possibly re-acquired, in several lines of passerine
birds, where ability to make vitamin C varies from species to species. In addition, GULO activity has also been lost in all types of bats, regardless of diet.
Loss of GULO activity in the primate
order occurred about 63 million years ago, at about the time it split into the suborders haplorrhini
(which lost the enzyme activity) and the more primitive strepsirrhini
(which retained it). The haplorrhini ("simple nosed") primates, which cannot make vitamin C enzymatically, include the tarsiers and the simians (apes, monkeys and humans). The suborder strepsirrhini (bent or wet-nosed prosimians), which are still able to make vitamin C enzymatically, include loris
es, galago
s, potto
s, and, to some extent, lemur
s.
L-gulonolactone oxidase deficiency is called "hypoascorbemia" and is described by OMIM (Online Mendelian Inheritance in Man) as "a public inborn error of metabolism", as it affects all humans. There exists a wide discrepancy between the amounts of ascorbic acid other primates consume and what is recommended as "reference intakes" for humans. In its patently pathological form, the effects of ascorbate deficiency are manifested as scurvy
.
EC number
The Enzyme Commission number is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze....
1.1.3.8) is an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that catalyzes the reaction
Chemical reaction
A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...
of D-glucuronolactone
Glucuronolactone
Glucuronolactone is a naturally occurring chemical that is an important structural component of nearly all connective tissues. Glucuronolactone is also found in many plant gums.- Physical and chemical properties :...
(also known as L-gulono-1,4-lactone) with oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
to L-xylo-hex-3-gulonolactone and hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...
. It uses FAD
FAD
In biochemistry, flavin adenine dinucleotide is a redox cofactor involved in several important reactions in metabolism. FAD can exist in two different redox states, which it converts between by accepting or donating electrons. The molecule consists of a riboflavin moiety bound to the phosphate...
as a cofactor
Cofactor (biochemistry)
A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....
. The L-xylo-hex-3-gulonolactone (2-keto-gulono-gamma-lactone) is able to spontaneously convert to hexuronic acid (ascorbic acid
Ascorbic acid
Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
), without enzymatic action.
Gulonolactone oxidase deficiency
The non-functional gulonolactone oxidase pseudogene (GULOP) was mapped to human chromosomeChromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
8p21
Chromosome 8 (human)
Chromosome 8 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 8 spans about 145 million base pairs and represents between 4.5 and 5.0% of the total DNA in cells....
that corresponds to an evolutionarily conserved segment on either porcine chromosome 4 (SSC4) or 14 (SSC14). GULO produces the precursor to ascorbic acid
Ascorbic acid
Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
, which spontaneously converts to the vitamin ("vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
").
The loss of activity of the gene for L-gulonolactone oxidase (GULO) has occurred separately in the history of several species. The loss of this enzyme activity is responsible for the inability of guinea pig
Guinea pig
The guinea pig , also called the cavy, is a species of rodent belonging to the family Caviidae and the genus Cavia. Despite their common name, these animals are not in the pig family, nor are they from Guinea...
s to enzymatically synthesize vitamin C, but this event happened independently of the loss in the haplorrhini
Haplorrhini
The haplorhines, the "dry-nosed" primates , are members of the Haplorhini clade: the prosimian tarsiers and the anthropoids...
suborder of primates, including humans. The remains of this non-functional gene with many mutations is, however, still present in the genome of the guinea pigs and in humans. The function of GULO appears to have been lost several times, and possibly re-acquired, in several lines of passerine
Passerine
A passerine is a bird of the order Passeriformes, which includes more than half of all bird species. Sometimes known as perching birds or, less accurately, as songbirds, the passerines form one of the most diverse terrestrial vertebrate orders: with over 5,000 identified species, it has roughly...
birds, where ability to make vitamin C varies from species to species. In addition, GULO activity has also been lost in all types of bats, regardless of diet.
Loss of GULO activity in the primate
Primate
A primate is a mammal of the order Primates , which contains prosimians and simians. Primates arose from ancestors that lived in the trees of tropical forests; many primate characteristics represent adaptations to life in this challenging three-dimensional environment...
order occurred about 63 million years ago, at about the time it split into the suborders haplorrhini
Haplorrhini
The haplorhines, the "dry-nosed" primates , are members of the Haplorhini clade: the prosimian tarsiers and the anthropoids...
(which lost the enzyme activity) and the more primitive strepsirrhini
Strepsirrhini
The clade Strepsirrhini is one of the two suborders of primates. Madagascar's only non-human primates are strepsirrhines, and others can be found in southeast Asia and Africa...
(which retained it). The haplorrhini ("simple nosed") primates, which cannot make vitamin C enzymatically, include the tarsiers and the simians (apes, monkeys and humans). The suborder strepsirrhini (bent or wet-nosed prosimians), which are still able to make vitamin C enzymatically, include loris
Loris
Loris is the common name for the strepsirrhine primates of the subfamily Lorisinae in family Lorisidae. Loris is one genus in this subfamily and includes the slender lorises, while Nycticebus is the genus for the slow lorises....
es, galago
Galago
Galagos , also known as bushbabies, bush babies or nagapies , are small, nocturnal primates native to continental Africa, and make up the family Galagidae...
s, potto
Potto
The potto is a strepsirrhine primate from the Lorisidae family. It is the only species in genus Perodicticus...
s, and, to some extent, lemur
Lemur
Lemurs are a clade of strepsirrhine primates endemic to the island of Madagascar. They are named after the lemures of Roman mythology due to the ghostly vocalizations, reflective eyes, and the nocturnal habits of some species...
s.
L-gulonolactone oxidase deficiency is called "hypoascorbemia" and is described by OMIM (Online Mendelian Inheritance in Man) as "a public inborn error of metabolism", as it affects all humans. There exists a wide discrepancy between the amounts of ascorbic acid other primates consume and what is recommended as "reference intakes" for humans. In its patently pathological form, the effects of ascorbate deficiency are manifested as scurvy
Scurvy
Scurvy is a disease resulting from a deficiency of vitamin C, which is required for the synthesis of collagen in humans. The chemical name for vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus, which also provides the adjective scorbutic...
.
See also
- Ascorbic acidAscorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
/Vitamin CVitamin CVitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress... - OxidoreductaseOxidoreductaseIn biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule to another...
- ScurvyScurvyScurvy is a disease resulting from a deficiency of vitamin C, which is required for the synthesis of collagen in humans. The chemical name for vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus, which also provides the adjective scorbutic...