Clinical aspects of urea cycle dysfunction and altered brain energy metabolism on modulation of glutamate receptors and transporters in acute and chronic hyperammonemia.
In living organisms, nitrogen arise primarily as ammonia (NH3) and ammonium (NH4(+)), which is a main component of the nucleic acid pool and proteins. Although nitrogen is essential for growth and maintenance in animals, but when the nitrogenous compounds exceeds the normal range which can quickly lead to toxicity and death. Urea cycle is the common pathway for the disposal of excess nitrogen through urea biosynthesis. Hyperammonemia is a consistent finding in many neurological disorders including congenital urea cycle disorders, reye's syndrome and acute liver failure leads to deleterious effects. Hyperammonemia and liver failure results in glutamatergic neurotransmission which contributes to the alteration in the function of the glutamate-nitric oxide-cGMP pathway, modulates the important cerebral process. Even though ammonia is essential for normal functioning of the central nervous system (CNS), in particular high concentrations of ammonia exposure to the brain leads to the alterations of glutamate transport by the transporters. Several glutamate transporters have been recognized in the central nervous system and each has a unique physiological property and distribution. The loss of glutamate transporter activity in brain during acute liver failure and hyperammonemia is allied with increased extracellular brain glutamate concentrations which may be conscientious for the cerebral edema and ultimately cell death.
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu 608002, India. Electronic address: nvkbiochem@yahoo.co.in.
Vijayakumar
V
Natesan
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu 608002, India.
Renuka
R
Mani
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu 608002, India.
Ramakrishnan
R
Arumugam
D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004734:Energy Metabolism; D006801:Humans; D022124:Hyperammonemia / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism*; D014508:Urea / Q000378:metabolism*
D027322:Amino Acid Transport System X-AG; D017470:Receptors, Glutamate; D014508:Urea
Glutamate; Glutamate receptors; Glutamate transporters; Hyperammonemia; Urea cycle