Biosynthetic Studies on Tropolones and Corrins : 이은

국문 초록 (Abstract)

페니실리움계통의 곰팡이가 생성하는 트로필론들, 즉 스티피타톤산이나 퓨버룰론산 은 방향족 여섯원자고리화합물들이 고리확장반응을 일으켜 일곱원자고리를 만드는 과 정을 거쳐서 생합성되는 것을 확인하였다. 프로피오니박테리움에 존재하는 효소혼합물 들이 S-아미노레불린산이나 유로포르피리노젠 Ⅲ를코비리닉산으로 변환시키는 것을 발 견하였다. 이것은 비타민 B��＠�생합성의 주요과정을 효소단계에서 처음으로 실현한 것이다.

다국어 초록 (Multilingual Abstract)

Recent evidence suggests that hypertension in insulin
resistant states may result from impaired insulin regulation
of vascular smooth muscle cell (VSMC) Ca2+ transport.
Insulin has previously been shown to attenuate
vasoconstrictor responses to pressor agonists and accelerate
vascular smooth muscle (VSM) relaxation and VSM Ca2+ efflux.
To further determine the role of insulin in regulatin g VSMC
Ca2+, quiescent A7r5 cultured VSMC and human VSMC loaded
with fura 2-AM were incubated with or without 10-7 or 10-8 M
insulin for 1 hour; intracellular Ca2+ ([Ca2+]i) responses to
and rates of recovery from angiotensin II (AII) (200 nM ) and
arginine vasopressin (AVP) were studied fluorometrically in
stirred suspension. Insulin caused an increase in the peak
[Ca2+]i response to AI1 (Peak/baseline X 100=469*9 6 versus 288+74 , pcO.05) and a decrease in the peak Ca" response to
AVP (288+50 versus 389233, pcO.025). However, insulin also
caused a marked increase in the rate of [Ca*'li recovery to
baseline after stimulation with both AI1 (77.3k13.8 versus
30.6+6 nM/min , pcO.03) and AVP (pcO.OS), such that the
cumulative exposure to elevated [Ca2+li after stimulation
with either agonist (i.e., area under the ECa"li response
curve) was reduced with insulin treatment. Insulin also
caused comparable effects on Ca2' recovery in the human
cells but was without significant effect on peak Ca"
responses to AVP. It is concluded that accelerated removal
of cytosolic Ca2 * after agonist stimulation is likely to
contribute to insulin attenuation of vasoconstrictor
responses and acceleration of vascular relaxation. To
evaluate the linkage between this insulin-regulation of VSMC
[Ca'+]i and classical action s of insulin (i.e. glucose
transport and metabolism), cultured VSMCs s were incubated in
the presence or absence of insulin in a medium containing
either pyruvate, glucose, 3-0-methylglucose (3-0-MG) or 2-
deoxyglucose (2-DG). Insulin caused a 87% increase in
[Ca2']i recovery rate following stimulation with AVP
(~~0.01) and caused a marked increase in both plasmalemma
and sarcoplasmic reticulum Ca'* -ATPase gene expression in
the presence of glucose. Comparable increases in both
[Ca'+]i recovery and Ca2 +-ATPase expression were found when
glucose was replaced by 2-deoxyglucose. In contrast, no stimulation was found in either the glucose-free or 3-0-methylglucose-containing medium. Since both glucose
analogues are transported, but only 2-DG is phosphorylated,
this indicates that glucose transport and metabolism to
glucose-6-phosphate is essential for insulin regulation of
VSMC [Ca"]i, possibly via a glucose-6-phosphate-dependent
carbohydrate response element in the Ca'*-ATPase gene.