Control of 6-(D-threo-1',2'-dihydroxypropyl) pterin (dictyopterin) synthesis during aggregation of Dictyostelium discoideum. Involvement of the G-protein-linked signalling pathway in the regulation of GTP cyclohydrolase I activity.
6-(D-threo-1',2'-Dihydroxypropylpterin (dictyopterin) has been identified in extracts of growing Dictyostelium dicoideum cells [Klein, Thiery and Tatischeff (1990) Eur. J. Biochem. 187, 665-669]. We demonstrate that it originates from GTP by de novo biosynthesis and that the first committed step is catalysed by GTP cyclohydrolase I, yielding dihydroneopterin triphosphate [neopterin is 6-(D-erythro-1',2',3'-trihydroxypropyl) pterin]. The GTP cyclohydrolase I activity is found in the cytosolic fraction and in a membrane-associated form. The level of a 0.9 kb mRNA coding for GTP cyclohydrolase I decreases to about 10% of its initial value within 2 h after Dictyostelium cells start development induced by starvation. In the cytosolic fraction, the specific activities of GTP cyclohydrolase I, as well as the concentrations of (6R/S)-5,6,7,8-tetrahydrodictyopterin (H4dictyopterin), follow this decline of the mRNA level. In the particulate fraction, however, the specific activities of GTP cyclohydrolase I and, in consequence, H4dictyopterin synthesis, transiently increase and reach a maximum after 4-5 h of development. The time-course of H4dictyopterin concentrations in the starvation medium closely correlates with its production in the membrane fraction. The activity of membrane-associated GTP cyclohydrolase I can be increased by pre-incubation of the cell lysate with guanosine 5'-[gamma-thio]triphosphate and Mg2+. This GTP analogue does not serve as a substrate and has no direct effect on the enzyme activity, indicating that a G-protein-linked signalling pathway is involved in the regulation of GTP cyclohydrolase I activity and thus in H4dictyopterin production during early development of D. discoideum.
Gütlich
M
M
GSF-Institut für Klinische Molekularbiologie und Tumorgenetik, München, Germany.
Witter
K
K
Bourdais
J
J
Veron
M
M
Rödl
W
W
Ziegler
I
I
D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000096:biosynthesis*; D015152:Blotting, Northern; D002851:Chromatography, High Pressure Liquid; D004023:Dictyostelium / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D004789:Enzyme Activation; D006136:GTP Cyclohydrolase / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015870:Gene Expression; D006160:Guanosine Triphosphate / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019761:Phosphorus-Oxygen Lyases; D011622:Pterins / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D011622:Pterins; D012333:RNA, Messenger; D001708:Biopterins; D006160:Guanosine Triphosphate; D000429:Alcohol Oxidoreductases; C022630:sepiapterin reductase; D006136:GTP Cyclohydrolase; D019204:GTP-Binding Proteins; D019761:Phosphorus-Oxygen Lyases; C043497:6-pyruvoyltetrahydropterin synthase; C003402:sapropterin