Mildly compromised tetrahydrobiopterin cofactor biosynthesis due to Pts variants leads to unusual body fat distribution and abdominal obesity in mice

Journal of Inherited Metabolic Disease
Germaine KornerBeat Thöny

Abstract

Tetrahydrobiopterin (BH4) is an essential cofactor for the aromatic amino acid hydroxylases, alkylglycerol monooxygenase, and nitric oxide synthases (NOS). Inborn errors of BH4 metabolism lead to severe insufficiency of brain monoamine neurotransmitters while augmentation of BH4 by supplementation or stimulation of its biosynthesis is thought to ameliorate endothelial NOS (eNOS) dysfunction, to protect from (cardio-) vascular disease and/or prevent obesity and development of the metabolic syndrome. We have previously reported that homozygous knock-out mice for the 6-pyruvolytetrahydropterin synthase (PTPS; Pts-ko/ko) mice with no BH4 biosynthesis die after birth. Here we generated a Pts-knock-in (Pts-ki) allele expressing the murine PTPS-p.Arg15Cys with low residual activity (15% of wild-type in vitro) and investigated homozygous (Pts-ki/ki) and compound heterozygous (Pts-ki/ko) mutants. All mice showed normal viability and depending on the severity of the Pts alleles exhibited up to 90% reduction of PTPS activity concomitant with neopterin elevation and mild reduction of total biopterin while blood L-phenylalanine and brain monoamine neurotransmitters were unaffected. Yet, adult mutant mice with compromised PTPS activity (i.e....Continue Reading

References

May 1, 1976·Journal of Clinical Pathology·R J LeemingD J O'Gorman
Jan 1, 1985·The American Journal of Clinical Nutrition·Y Matsubara, G E Gaull
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jun 11, 2002·Annual Review of Nutrition·Guoyao Wu, Cynthia J Meininger
May 6, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Nikolaj IhlemannChristian Torp-Pedersen
Jul 16, 2003·Journal of Neurochemistry·Bernadin Joseph, Charissa A Dyer
Dec 6, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Sharon C TaiPhilip A Marsden
Jul 22, 2004·American Journal of Physiology. Endocrinology and Metabolism·Thomas NyströmAke Sjöholm
Aug 4, 2004·European Journal of Nuclear Medicine and Molecular Imaging·Christophe A WyssPhilipp A Kaufmann
Oct 7, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Cynthia J MeiningerGuoyao Wu
Oct 29, 2004·Cell Biochemistry and Biophysics·Wenjuan ShiGuoyao Wu
Jan 22, 2005·Annual Review of Medicine·I Sadaf Farooqi, Stephen O'Rahilly
May 24, 2005·Nature Methods·Valérie Gailus-DurnerMartin Hrabé de Angelis
Apr 6, 2006·Circulation·Ulrich Förstermann, Thomas Münzel
Nov 14, 2006·European Journal of Pharmacology·Xi WangKikuo Kasai
Dec 15, 2006·Nature·Jean-Pierre Després, Isabelle Lemieux
Mar 7, 2009·Methods in Molecular Biology·Valérie Gailus-DurnerMartin Hrabé de Angelis
Aug 11, 2010·Biochemical and Biophysical Research Communications·Hyun Jin ParkMyeong Ho Jung
Oct 26, 2010·Lancet·Nenad BlauHarvey L Levy
Dec 15, 2010·Current Vascular Pharmacology·Salvatore De RosaMassimo Chiariello
Aug 27, 2011·The Biochemical Journal·Ernst R WernerBeat Thöny
Mar 30, 2012·The Journal of Endocrinology·Paramita M GhoshAmrita Kamat
Oct 12, 2012·Thrombosis and Haemostasis·Eileen McNeill, Keith M Channon
Jan 26, 2013·Diabetes·Kyoichiro Tsuchiya, Domenico Accili
May 23, 2014·Diabetes·Deimante SimaiteKlemens Raile

❮ Previous
Next ❯

Citations

Jun 24, 2017·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Benjamin S Pickard
Feb 6, 2020·Focus : Journal of Life Long Learning in Psychiatry·Benjamin S Pickard
Apr 30, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Hyoung Kyu Kim, Jin Han

❮ Previous
Next ❯

Related Concepts

Related Feeds

Asprosin

Asprosin is a fasting-induced hormone produced in the white adipose tissue to stimulate the hepatic release of glucose into the bloodstream. Discover the latest research on this protein hormone here.