Project Title:
14.
Scope:
Nuclear Medicine Technology and Other Health Applications
Metabolism of Carbon Labeled Compounds
RX-01-03-(e)
(Cont'd)
tunity to investigate formation, turnover, and (uniquely possible with
C-13) even chemical structure of complex carbohydrates in serum glycoproteins, most of which contain galactose.
Other studies with labeled sugars are concerned with lipogenesis
in the liver and with plasma lipid formation and removal.
The differences
between starch and sucrose in their lipogenic and insulinogenic potential
are presently under investigation with human subjects.
These studies
(with sucrose-C-14, glycerol-H-3, and occasionally C-ll-labeled sugars)
help to clarify mechanisms of susceptibility to hyperlipemia and hyperinsulinism as affected by different diet (e.g., low or high sucrose)
or by steroids.
Possibly they can identify particular susceptibilities
in individual patients.
In this case, C-13 may be valuable diagnostically
in this area.
Because of known or suspected changes in diabetes and in steroid-
treated subjects, the metabolism of tryptophan-C-13 (or of tryptophan-C-14)
to 13¢0 {or 1 COz) and to intermediate metabolites in accessible body
fluids will be examined in such patients.
This unexplored direction may
provide new diagnostic parameters in certain metabolic diseases, in vitamin
deficiencies, e.g., pellagra, and in distrubances of the central nervous
system.
(Shreeve);
The following work was funded for FY 1973 and reported in
RX-O1-03(c})
(old code 06-03-Ol-c) but is reported here also for convenient
reference in relation to work in future years.
The objective of the project studying tryptophan metabolism in
normal animals and man and in various diseases using tryptophan metabolites
labeled in different positions of their structure with carbon-14 is to
see if there is any cause-effect relationship in the diseases studied.
The literature reports show that in several types of cancer patients
and patients with other diseases a significant increase occurred in the
levels of acetylkynurenine, kynurenine, kynurenic acid, hydroxykynurenine,
xanthurenic acid, and quinolinic acid.
The tryptophan metabolites, anthranilic acid carboxy1-C-14,
kynurepine-keto-C-14, kynurenine-ring-2-C-14, hydroxykynurenine-keto-C-14,
foxyanthranilic acid-carboxyl-C-14 have been synthesized. Procedures
Kected which utilized columns filled with paper pulp for the
ym of small quantities of the L- and D-isomers of tryptophan,
kynurenine, and hydroxykynurenine.
Size and resolving power of the
columns limit the quantity of material which may be resolved (50-300 mg)
and meet FDA specifications. These factors in turn limit the number and
the rate at which studies may be done. The metabolism of carbon-14 labeled
(See Continuation Sheet)
117192349
RX-81
.