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Q J Med 1999; 92: 495-503
© 1999 Association of Physicians

Hyperphenylalaninaemia in children with falciparum malaria

C.O. Enwonwu1,2, B.M. Afolabi3, L.A. Salako3, E.O. Idigbe3, H. Al-Hassan4 and R.A. Rabiu5

1 From the Departments of OCBS, School of Dentistry, and 2 Biochemistry, School of Medicine, University of Maryland, Baltimore, Maryland, USA, 3 Nigerian Institute of Medical Research, Lagos, 4 Specialist Hospital, Sokoto, and 5 Massey Street Children Hospital, Lagos, Nigeria

Received 5 February 1999 and in revised form 5 July 1999

Professor C.O. Enwonwu, Departments of Biochemistry and OCBS, Schools of Medicine and Dentistry, 666 West Baltimore Street, Room 4G31, Baltimore, MD 21201-1586, USA

Brain monoamine levels may underlie aspects of the cerebral component of falciparum malaria. Since circulating amino acids are the precursors for brain monoamine synthesis, we measured them in malaria patients and controls. Malaria elicited significantly elevated plasma levels of phenylalanine, particularly in comatose patients, with the Tyr/Phe (%) ratio reduced from 83.3 in controls to 39.5 in infected children, suggesting an impaired phenylalanine hydroxylase enzyme system in malaria infection. Malaria significantly increased the apparent Km for Trp, Tyr and His, with no effect on Km(app) for Phe. Using the kinetic parameters of NAA transport at the human blood–brain barrier, malaria significantly altered brain uptake of Phe (+96%), Trp (-28%) and His (+31%), with no effect on Tyr (-8%), compared with control findings. Our data suggest impaired cerebral synthesis of serotonin, dopamine and norepinephrine, and enhanced production of histamine, in children with severe falciparum malaria.


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