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, respo ...

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 ba ...

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 use ...

protein catalyzes the conversion of pyrroline-5-carboxylate to

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...

, 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, 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 Pyrroline-5-carboxylate reductase 1, mitochondrial is an enzyme that in humans is encoded by the ''PYCR1'' gene. This gene encodes an enzyme that catalyzes the NAD(P)H-dependent conversion of pyrroline-5-carboxylate to proline. This enzyme may al ...

, 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 A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

, and in much higher forms than either of the other two isoforms. Although PYCR2 is an enzyme for

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 Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances ...

. The PYCR family also has been correlated with melanoma cells. PYCR2 as well as PYCR are abundant in

melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...

cells but not detected in melanocytes.

Function

Clinical significance

References

Further reading