Pyrroline-5-carboxylate reductase family, member 2 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...
that in humans is encoded by the PYCR2
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Function
This gene belongs to the
pyrroline-5-carboxylate reductase
In enzymology, a pyrroline-5-carboxylate reductase () is an enzyme that catalyzes the chemical reaction
:L-proline + NAD(P)+ \rightleftharpoons 1-pyrroline-5-carboxylate + NAD(P)H + H+
The 3 substrates of this enzyme are L-proline, NAD+, and ...
family. The encoded
mitochondrial
A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...
protein catalyzes the conversion of pyrroline-5-carboxylate to
proline, which is the last step in proline biosynthesis.
Loss of PYCR2 does not lead to a gross defect in mitochondrial protein synthesis, but loss of function of PYCR2 leads to increased apoptosis under oxidative stress.
Clinical significance
Mutations in the PYCR2 gene have been identified as the cause of a unique syndrome characterized by postnatal
microcephaly
Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it ...
,
hypomyelination
Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be l ...
, and reduced cerebral white-matter volume. Hypomyelination and the absence of wrinkly skin makes this condition distinct from that caused by previously reported mutations in the gene encoding PYCR2’s isozyme,
PYCR1, suggesting a unique and indispensable role for PYCR2 in the human CNS during development. This is substantiated by the fact that PYCR2 mRNA is moderately expressed in the developing human
brain
The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head ( cephalization), usually near organs for special ...
, and in much higher forms than either of the other two isoforms. Although PYCR2 is an enzyme for
proline biosynthesis, systemic deprivation of proline does not appear to be the pathogenetic mechanism of this condition, given that plasma amino acid analysis in two affected individuals did not show low proline levels. Furthermore, mitochondrial protein synthesis was not affected in PYCR2-deficient cells. Therefore, deficiency of proline, as a building block of proteins, might not be the major pathophysiology. However, proline has been reported as a non-enzymatic antioxidant that suppresses apoptosis, and therefore local proline biosynthesis in neurons might be important for neuronal protection against
oxidative stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal re ...
.
The PYCR family also has been correlated with melanoma cells. PYCR2 as well as PYCR are abundant in
melanoma cells but not detected in melanocytes.
References
Further reading
*
*
{{gene-1-stub