IPA Pathway assignment

Searching IPA Pathways for my gene "PAH".

Ingenuity Pathway Analysis: It is one of the best knowledge discovery and functional analysis tools.
Identifies the metabolic pathways, molecular networks and biological functions for a list of genes. Predicts the activation and inhibition of the transcription factors,as well as the biological and disease processes. IPA compares the affected pathways and phenotypes across multiple testing conditions.

http://norris.usc.libguides.com/IPA

There are two  drugs associated with the product of  PAH  called "5,6,7,8-tetrahydrobiopterin" and "sapropterin". The first drug  "5,6,7,8-tetrahydrobiopterin "  belongs to the category of "metabolic disorder drug". It's brand name is "Kuvan".

Drugs associated with PAH

I grew the pathways associated with PAH in humans only and which were directly related to my gene only while the all the disease were considered the biologic drugs and the 8 molecules were removed.
When the stringent filter was applied only one molecule called "Cyclin D1" located in the nucleus and associated with the family of transcription regulator and one relationship " E1" involved in the expression of human PAH mRNA was added to the gene.

 

I allowed the pathway to grow  and let all the molecules add to the newly formed pathway. This allowed the addition of 370 new molecules and 370 new relationships.
 
370 molecules and relationship grew
I applied the trim option after selecting all the molecules and  removing one relationship "Expression" and 372 molecules and 371 relationships were removed. There was nothing seen on the screen following is the screen shot.

372 molecules and 371 relationships removed after TRIM
 
The screen shot of the autolayout when a relaxed filter was used.
 

 There is only one relationship connected to my gene. It is expression relationship where Cyclin d1 (CCND1) mRNA (Nucleus)  by siRNA is involved in expression of human Phenylalanine Hydroxylase (cytoplasm).
 
 
There are no (zero)  Activation, Inhibition, or Protein -Protein Interaction relationship types connect to PAH.

The toggle subcellular layout screen shot looks like as under.
 

There are two Canonical pathways associated with PAH.
  • Phenylalanine Degradation I (Aerobic).
  • Tyrosine Biosynthesis IV.

Function of the Tyrosine Biosynthesis pathway. In humans L-Phenylanaline is an essential amino acid, it is either used for the synthesis of proteins or is converted to another amino acid L-tyrosine which is the precursor for catecholamine and thyroid hormone synthesis. The active tetramaric form of Phenylalanine Hydroxylase (PAH) is produced and the L-phenylalanine and tetryhydrobiopterin bind to the active site of the PAH and the catalysis  to L-tyrosine will occurr.

 
Phenylalanine hydroxylase (PAH) is an enzyme that catalyzes the hydroxylation of the aromatic side-chain of phenylalanine to generate tyrosine. PAH is pterin-dependent amino acid hydroxylases that uses tetrahydrobiopterin (BH4, a pteridine cofactor) and a non-heme iron for catalysis. Molecular oxygen is heterolytically cleaved with sequential incorporation of one oxygen atom into BH4 and phenylalanine substrate.
Phenylalanine hydroxylase is the rate-limiting enzyme of the metabolic pathway that degrades excess phenylalanine, mutations in PAH the encoding gene, can lead to a severe metabolic disorder called phenylketonuria.

References:

 







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