1.5.1.2	evolution	enzymes that reduce DELTA1-pyrroline-5-carboxylate and DELTA1-piperideine-6-carboxylate are aldimine reductases whereas enzymes that reduce DELTA1-piperideine-2-carboxylate and DELTA1-pyrroline-2-carboxylate (P2C/Pyr2C) are ketimine reductases (KRs)	743355	
1.5.1.2	malfunction	homozygous mutations in human PYCR2 lead to postnatal microcephaly and hypomyelination, including hypomyelinating leukodystrophy type 10. PYCR2 mutations are detected in patients with lethal microcephaly, loss of PYCR2 is proposed to impair mitochondria function and disrupt oxidative balance, namely NAD(P)+ levels. The R251C variant displays the least overall regular alpha-helical character of the PYCR2 proteins, yet the R251C variant also displays strong overall regular beta-strand or beta-sheet character	762678	
1.5.1.2	metabolism	catalyzes step 7 in the ornithine fermentation pathway	704292	
1.5.1.2	metabolism	mammalian tissues contain a Pyr5C/P6C reductase that is distinct from Pyr2C/P2C reductase. In higher eukaryotes Pyr5C is also generated by a mitochondrial isozyme Pyr5C synthetase (isozyme PYCR1, UniProt ID P32322). Lysine/ornithine catabolism and interconnected pathways with 5-carbon amino acid (L-glutamate gamma-semialdehyde, L-glutamate, L-ornithine, L-proline) metabolism in mammalian tissues, overview. Although the ketimine reductase (KR) is important in the formation of L-pipecolate in the brain, it is also an important source of L-proline. This proline (via proline oxidase) in turn is an important source of Pyr5C and hence of glutamate and to a lesser extent ornithine	743355	
1.5.1.2	metabolism	sequential binding mechanism with 1-pyrroline-5-carboxylate binding before NAD(P)H and NAD(P)+ releasing before L-Pro	762678	
1.5.1.2	metabolism	the enzyme is involved in the proline metabolism in the mitochondrion, overview	762678	
1.5.1.2	physiological function	L-proline has important roles in mammalian bioenergetics, cellular redox control, apoptosis and cancer. In mammals, Pyr5C reductase exists in two isoforms: a short form is present in the intestine that is feedback inhibited by ornithine and may be important in the synthesis of L-arginine from L-glutamate in the intestine. On the other hand, most other tissues express a long form of DELTA1-pyrroline-5-carboxylate reductase, which is thought to be important in the synthesis of L-proline from L-glutamate	743355	
1.5.1.2	physiological function	PYCR2 knockdown reduces cell viability, proliferation, migration, and invasion and increases apoptosis. PYCR2 knockdown increases Bax, cleaved caspase-3, and cleaved PARP levels and decreases Bcl-2, MMP-2, MMP-9, p-PI3K, p-AKT, and p-mTOR levels in colorectal cancer cells	762952	
1.5.1.2	physiological function	pyrroline-5-carboxylate reductase (PYCR in humans) catalyzes the final step of L-proline biosynthesis by catalyzing the reduction of L-DELTA1-pyrroline-5-carboxylate (L-P5C) to L-proline using NAD(P)H as the hydride donor. In humans, three isoforms PYCR1c, and PYCR3 are known. Isozyme PYCR3 is a cytosolic enzyme whereas PYCR1 and PYCR2 are identified as mitochondrial isozymes. PYCR2 not only drives cellular supply of L-proline but it is also important for redox cycling of NAD(P)H/NAD(P)+	762678	
1.5.1.2	physiological function	treatment with oxidized low-density lipoproteins decreases the cell number per field and causes the cells to round up. Knock-down of proline oxidase via small interfering RNA further reduces viability of cancer cells treated with oxidized low-density lipoproteins, decreases oxidized low-density lipoproteins-associated reactive oxygen species generation, decreases autophagy measured via beclin-1 protein level and light-chain 3 protein-I into LC3-II conversion. Single proline oxidase overexpression is sufficient to activate autophagy. It leads to autophagosomes accumulation and increases conversion of LC3-I into LC3-II.Beclin-1 gene expression is directly dependent on proline oxidase catalytic activity, namely the generation of prloine-oxidase-dependent superoxide	711685