Sažeci 2. Hrvatskog kongresa medicinske biokemije - Klinički zavod ...

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Sažeci 2. Hrvatskog kongresa medicinske biokemije
SEKCIJSKA PREDAVANJA
S4/1
NOVEL OBSERVATIONS ON NITRIC OXIDE BIOLOGY:
AMINO ACID TRANSPORT AND THE IMMUNE
SYSTEM
C.A.R. Boyd
Department of Human Anatomy, University of Oxford, Oxford, UK
Nitric oxide (NO) has unexpectedly been found to have a critical
role in cell signalling, for example in the brain, in the immune response,
in cardiovascular and reproductive physiology. When the biosynthetic
pathways of NO production are activated, production of NO
can cause important clinical problems (e.g. septic shock). The cationic
amino acids arginine, lysine and histidine were shown more than 20
years ago to be transported in animal cells by a system (called y + )
which was characterised by its independence of extracellular sodium
ions and its ability to translocate in addition to these three amino
acids some neutral amino acids (e.g. homoserine) in the presence of
sodium. Over the last 5 years there have been three major developments.
The molecular identification of system y + as being via the CAT
family of gene products (having twelve transmembrane domains)
which have 3 characterized gene products (CAT1, CAT2A, CAT2B);
the realisation that in addition to y + there are transporters of very
high affinity for a broader range of amino acids as substrates
(systems y + L, b + 0 ) which are clearly distinct from system y + ; and the
understanding that arginine delivery, required as the substrate for
NO biosvnthesis, may be rate-limiting for NO production, i.e. that
the rate of cationic amino acid transport across the plasma membrane
may regulate NO production. Recent experiments show transport of
arginine to be a potential site for the regulation of tissue-specific NO
production and thus a target for therapeutic intervention for pathological
circumstances associated with abnormalities resulting from
stimulated NO production. Results of preliminary work on sepsis
patients will be reviewed with respect to observed alterations in
cationic amino acids transport found in human peripheral blood mononuclear
cells.
52 BIOCHEMIA MEDICA god. 6, br. 1, 1996.