Disease relevance of pipecolate

• The distinctive astrocytic storage phenomenon and the liver changes are compared to the findings in Zellweger's syndrome and lysinuric protein intolerance, which are also associated with altered pipecolate metabolism [1].
• The pipecolate-incorporating enzyme for the biosynthesis of the immunosuppressant rapamycin--nucleotide sequence analysis, disruption and heterologous expression of rapP from Streptomyces hygroscopicus [2].

High impact information on pipecolate

• Elucidating the substrate specificity and condensation domain activity of FkbP, the FK520 pipecolate-incorporating enzyme [3].
• A pipecolate-dependent decarboxylation of [1-14C]malonate was demonstrated in cell-free extracts of R. leguminicola [4].
• The absence of the gene encoding lysine cyclodeaminase in the sequenced gene cluster and the rest of the genome of NRRL 30748 indicated the synthesis of pipecolate in this strain is not through the common lysine cyclodeamination route previously described for rapamycin and FK506/FK520 biosynthesis [5].
• [structure: see text] 2-Aryl-2,2-difluoroacetamido-proline and pipecolate esters are high affinity FKBP12 ligands whose rotamase inhibitory activity is comparable to that seen for the corresponding ketoamides [6].
• A third gene, fkbL, lies at one end of the cluster and encodes lysine cyclodeaminase which catalyzes alpha-deamination and cyclization of the lysine into pipecolate [7].

Biological context of pipecolate

• Three early D-lysine catabolic enzymes encoded by the OCT plasmid are a lysine racemase, the proposed conversion of D-lysine to delta 1-piperidine-2-carboxylate (P2C), for which we provide evidence, and P2C reductase which converts P2C to pipecolate [8].

Anatomical context of pipecolate

• The metabolic pathways in which peroxisomes are involved include the biosynthesis of ether phospholipids and bile acids, the oxidation of very long chain fatty acids, prostaglandins and unsaturated long chain fatty acids and the catabolism of phytanate and (in man) pipecolate and glyoxylate [9].

Associations of pipecolate with other chemical compounds

• In the presence of added proline derivatives, rapL mutants synthesized novel rapamycin analogs, indicating a relaxed substrate specificity for the enzyme catalyzing pipecolate incorporation into the macrocycle [10].

Gene context of pipecolate

• A series of novel, selective TNF-alpha converting enzyme inhibitors based on 4-hydroxy and 5-hydroxy pipecolate hydroxamic acid scaffolds is described [11].
• Surprisingly, in spite of the requirement for the wild-type proX gene for osmoprotective ability, no binding activity of labelled pipecolate with the periplasmic protein encoded by proX could be detected [12].
• The pipecolate region which extends from C24 to C10 including the pipecolate ring shows strongly conserved conformation in both solvents [13].

Analytical, diagnostic and therapeutic context of pipecolate

• Ten of twelve immunomycin nonproducing mutants lack detectable pipecolate-activating enzyme in Western blots [14].

References