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A developmental change in dolichyl phosphate mannose synthase activity in pig brain
The Biochemical Journal
|May 15, 1980
Summary
Dolichyl phosphate mannose synthase activity in pig brain membranes peaks during rapid development, with adult brains showing lower activity due to reduced accessible endogenous dolichyl monophosphate.
Area of Science:
- Biochemistry
- Neuroscience
- Developmental Biology
Background:
- Dolichyl phosphate mannose (Dol-P-Man) is crucial for N-glycosylation, a vital process in brain development.
- Dolichyl phosphate mannose synthase (DPMS) catalyzes Dol-P-Man biosynthesis.
- Understanding DPMS developmental regulation is key to comprehending brain maturation.
Purpose of the Study:
- To investigate the developmental changes in dolichyl phosphate mannose biosynthesis rate in pig brain white-matter membranes.
- To elucidate the biochemical basis for the observed developmental regulation of DPMS activity.
Main Methods:
- Measurement of initial rates of Dol-P-Man biosynthesis in white-matter membranes from pigs at various developmental stages.
- Enzymatic and biochemical characterization of DPMS activity using varying substrate concentrations and lipid acceptor availability.
- Comparison of DPMS activity in membranes from actively myelinating (3-week-old) and adult animals.
Main Results:
- DPMS activity increased from prenatal levels to a maximum at 3 weeks, then declined to adult levels after 8 weeks.
- Specific DPMS activity was ~3-fold higher in actively myelinating animals compared to adults when using endogenous acceptor lipid.
- Apparent K(m) values for substrates did not significantly vary, but the activity ratio decreased with added exogenous dolichyl monophosphate.
- DPMS activity in dolichyl monophosphate-depleted membranes showed a smaller increase in myelinating animals, suggesting endogenous lipid availability is critical.
Conclusions:
- Developmental changes in DPMS activity are primarily attributed to differences in the availability of endogenous dolichyl monophosphate.
- Adult white-matter membranes appear to have less accessible dolichyl monophosphate, limiting the synthase activity.
- This finding highlights the importance of lipid acceptor availability in regulating key glycosylation pathway enzymes during brain development.