TY - JOUR
T1 - Human de novo purine biosynthesis
AU - Pareek, Vidhi
AU - Pedley, Anthony M.
AU - Benkovic, Stephen J.
N1 - Funding Information:
We wish to thank Cyrielle Doigneaux and Ali Tavassoli for use of the proximity ligation assay images (). VP acknowledges financial support from the Huck Institutes of Life Sciences, PSU.
Funding Information:
This work was supported by the National Institutes of Health [grant number 5R01GM024129 to S.J.B.]. We wish to thank Cyrielle Doigneaux and Ali Tavassoli for use of the proximity ligation assay images (Figure 2(B)). VP acknowledges financial support from the Huck Institutes of Life Sciences, PSU.
Publisher Copyright:
© 2020 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021
Y1 - 2021
N2 - The focus of this review is the human de novo purine biosynthetic pathway. The pathway enzymes are enumerated, as well as the reactions they catalyze and their physical properties. Early literature evidence suggested that they might assemble into a multi-enzyme complex called a metabolon. The finding that fluorescently-tagged chimeras of the pathway enzymes form discrete puncta, now called purinosomes, is further elaborated in this review to include: a discussion of their assembly; the role of ancillary proteins; their locus at the microtubule/mitochondria interface; the elucidation that at endogenous levels, purinosomes function to channel intermediates from phosphoribosyl pyrophosphate to AMP and GMP; and the evidence for the purinosomes to exist as a protein condensate. The review concludes with a consideration of probable signaling pathways that might promote the assembly and disassembly of the purinosome, in particular the identification of candidate kinases given the extensive phosphorylation of the enzymes. These collective findings substantiate our current view of the de novo purine biosynthetic metabolon whose properties will be representative of how other metabolic pathways might be organized for their function.
AB - The focus of this review is the human de novo purine biosynthetic pathway. The pathway enzymes are enumerated, as well as the reactions they catalyze and their physical properties. Early literature evidence suggested that they might assemble into a multi-enzyme complex called a metabolon. The finding that fluorescently-tagged chimeras of the pathway enzymes form discrete puncta, now called purinosomes, is further elaborated in this review to include: a discussion of their assembly; the role of ancillary proteins; their locus at the microtubule/mitochondria interface; the elucidation that at endogenous levels, purinosomes function to channel intermediates from phosphoribosyl pyrophosphate to AMP and GMP; and the evidence for the purinosomes to exist as a protein condensate. The review concludes with a consideration of probable signaling pathways that might promote the assembly and disassembly of the purinosome, in particular the identification of candidate kinases given the extensive phosphorylation of the enzymes. These collective findings substantiate our current view of the de novo purine biosynthetic metabolon whose properties will be representative of how other metabolic pathways might be organized for their function.
UR - http://www.scopus.com/inward/record.url?scp=85096110005&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85096110005&partnerID=8YFLogxK
U2 - 10.1080/10409238.2020.1832438
DO - 10.1080/10409238.2020.1832438
M3 - Review article
C2 - 33179964
AN - SCOPUS:85096110005
SN - 1040-9238
VL - 56
SP - 1
EP - 16
JO - Critical Reviews in Biochemistry and Molecular Biology
JF - Critical Reviews in Biochemistry and Molecular Biology
IS - 1
ER -