K**R
发帖数: 193 | 1 有什么方法能在实验中改变glycolysis rate？ |
h*******o
发帖数: 4884 | 2 in vitro or in vivo?
in vitro it is easy
You can use hexokinase inhibitor, such as 2-deoxyglucose,
You can use PDH activator, such as dicholoracetate
You can use Pyruvate transporter inhibitor, Thiazolidinediones
There are so many ways to manipulate cellular bioenergetic flux (glycolysis
or Mitochondrial OXPHOS), some may require digitonin or other similar
detergent to permeablize plasma membrane. |
p*****h
发帖数: 36 | 3 2-DG is a substrate of HK, not an inhibitor. But it cannot be further
metabolized by downstream enzymes. In this sense, it inhibits glycolysis.
DCA is dirty. So is TZD.
glycolysis
【在 h*******o 的大作中提到】
: in vitro or in vivo?
: in vitro it is easy
: You can use hexokinase inhibitor, such as 2-deoxyglucose,
: You can use PDH activator, such as dicholoracetate
: You can use Pyruvate transporter inhibitor, Thiazolidinediones
: There are so many ways to manipulate cellular bioenergetic flux (glycolysis
: or Mitochondrial OXPHOS), some may require digitonin or other similar
: detergent to permeablize plasma membrane.
|
h*******o
发帖数: 4884 | 4 2-DG can be considered as a suicide inhibitor of hexokinase, its
phosphoproduct by hexokinase, 2DG6P, inhibits hexokinase activity.
When dealing with metabolic flux, there is nothing that comes clean, that's
why such experiments need to be tightly controlled with multiple inhibitors/
reagents targeting different steps of metabolic pathway.
【在 p*****h 的大作中提到】
: 2-DG is a substrate of HK, not an inhibitor. But it cannot be further
: metabolized by downstream enzymes. In this sense, it inhibits glycolysis.
: DCA is dirty. So is TZD.
:
: glycolysis
|
p*****h
发帖数: 36 | 5 Suicide inhibitor is a term reserved for those capable of covalent
modification of enzyme active site. Of course at high concentrations, 2DG6P
as a substrate /product analogue inhibits several glycolytic enzymes
including HK and PFK.
It is for historical reasons that these drugs are dirty (phenotypic drug
screening came well before rational design). This is not to say there will
be no better drugs.
在 hellozero (hellozero) 的大作中提到: 】
s
inhibitors/ |
l**********1
发帖数: 5204 | 6 p53+TIGAR
PMID 19015259
J Biol Chem. 2009 284: 1748-54.
Structural and biochemical studies of TIGAR (TP53-induced glycolysis and
apoptosis regulator).
http://www.ncbi.nlm.nih.gov/pubmed/19015259
or
PMID 23999443
J Clin Invest. 2013 123: 3685-92.
Targeting lactate metabolism for cancer therapeutics.
http://www.ncbi.nlm.nih.gov/pubmed/23999443
【在 K**R 的大作中提到】
: 有什么方法能在实验中改变glycolysis rate？
|
K**R
发帖数: 193 | 7 暂时是invitro 多谢非常有用！
glycolysis
【在 h*******o 的大作中提到】
: in vitro or in vivo?
: in vitro it is easy
: You can use hexokinase inhibitor, such as 2-deoxyglucose,
: You can use PDH activator, such as dicholoracetate
: You can use Pyruvate transporter inhibitor, Thiazolidinediones
: There are so many ways to manipulate cellular bioenergetic flux (glycolysis
: or Mitochondrial OXPHOS), some may require digitonin or other similar
: detergent to permeablize plasma membrane.
|
h*******o
发帖数: 4884 | 8 any example of "clean" modulators of metabolic flux/glycolysis?
2DG6P
【在 p*****h 的大作中提到】
: Suicide inhibitor is a term reserved for those capable of covalent
: modification of enzyme active site. Of course at high concentrations, 2DG6P
: as a substrate /product analogue inhibits several glycolytic enzymes
: including HK and PFK.
: It is for historical reasons that these drugs are dirty (phenotypic drug
: screening came well before rational design). This is not to say there will
: be no better drugs.
: 在 hellozero (hellozero) 的大作中提到: 】
: s
: inhibitors/
|
h*******o
发帖数: 4884 | 9 pigfish was right, 2-DG usually is not called as hexokinase inhibitor but
glycolytic inhibitor.
There are many other metabolic modulators that you can use, but keep in mind
, they often come with primary and secondary impact of metabolic flux and
you should tightly control your study so that the outcome can be interpreted
properly.
【在 K**R 的大作中提到】
: 暂时是invitro 多谢非常有用！
:
: glycolysis
|
