PMID- 31105574
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 10
DP  - 2019
TI  - Propagation of Plasma L-Phenylalanine Concentration Fluctuations to the 
      Neurovascular Unit in Phenylketonuria: An in silico Study.
PG  - 360
LID - 10.3389/fphys.2019.00360 [doi]
LID - 360
AB  - Phenylketonuria (PKU) is an inherited metabolic disease characterized by 
      abnormally high concentrations of the essential amino acid L-phenylalanine (Phe) 
      in blood plasma caused by reduced activity of phenylalanine hydroxylase (PAH). 
      While numerous studies have shown association between high plasma Phe 
      concentration and intellectual impairment, it is not clear whether increased Phe 
      fluctuations also observed in PKU affect the brain as well. To investigate this, 
      time-resolved in vivo data on Phe and competing large neutral amino acid (LNAA) 
      concentrations in neurons are needed, but cannot be acquired readily with current 
      methods. We have used in silico modeling as an alternative approach to 
      characterize the interactive dynamics of Phe and competing LNAAs (CL) in the 
      neurovascular unit (NVU). Our results suggest that plasma Phe fluctuations can 
      propagate into the NVU cells and change there the concentration of LNAAs, with 
      the highest magnitude of this effect observed at low frequency and high 
      amplitude-to-mean ratio of the plasma Phe concentration fluctuations. Our model 
      further elucidates the effect of therapeutic LNAA supplementation in PKU, showing 
      how abnormal concentrations of Phe and CL in the NVU move thereby toward normal 
      physiologic levels.
FAU - Taslimifar, Mehdi
AU  - Taslimifar M
AD  - The Interface Group, Institute of Physiology, University of Zurich, Zurich, 
      Switzerland.
AD  - Epithelial Transport Group, Institute of Physiology, University of Zurich, 
      Zurich, Switzerland.
FAU - Buoso, Stefano
AU  - Buoso S
AD  - The Interface Group, Institute of Physiology, University of Zurich, Zurich, 
      Switzerland.
AD  - Institute for Diagnostic and Interventional Radiology, Zurich University 
      Hospital, Zurich, Switzerland.
FAU - Verrey, Francois
AU  - Verrey F
AD  - Epithelial Transport Group, Institute of Physiology, University of Zurich, 
      Zurich, Switzerland.
AD  - Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, 
      Switzerland.
AD  - National Center of Competence in Research, Kidney Control of Homeostasis, Zurich, 
      Switzerland.
FAU - Kurtcuoglu, Vartan
AU  - Kurtcuoglu V
AD  - The Interface Group, Institute of Physiology, University of Zurich, Zurich, 
      Switzerland.
AD  - Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, 
      Switzerland.
AD  - National Center of Competence in Research, Kidney Control of Homeostasis, Zurich, 
      Switzerland.
AD  - Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20190402
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC6454150
OTO - NOTNLM
OT  - L-phenylalanine fluctuation
OT  - amino acid transporter
OT  - large neutral amino acid
OT  - neurovascular unit
OT  - phenylketonuria
EDAT- 2019/05/21 06:00
MHDA- 2019/05/21 06:01
PMCR- 2019/04/02
CRDT- 2019/05/21 06:00
PHST- 2018/10/23 00:00 [received]
PHST- 2019/03/14 00:00 [accepted]
PHST- 2019/05/21 06:00 [entrez]
PHST- 2019/05/21 06:00 [pubmed]
PHST- 2019/05/21 06:01 [medline]
PHST- 2019/04/02 00:00 [pmc-release]
AID - 10.3389/fphys.2019.00360 [doi]
PST - epublish
SO  - Front Physiol. 2019 Apr 2;10:360. doi: 10.3389/fphys.2019.00360. eCollection 
      2019.