LECTURE 32 - TRANSCRIPTIONAL CONTROL OF METABOLISM Flashcards
what is homeostasis and what can disturbance of it lead to?
balance regulation of fuel intake storage and expenditure
disturbance: anorexia, obesity
can contribute to the aetiology of the metabolic syntron leading to diabetes, heart and kidney failure, fatty liver and cancer
what is progression of fatty liver disease to cancer
NAFL: non alcoholic fatty liver disease
NASH: non alcoholic steatohepatitis
how is metabolism controlled through short term regulation?
seconds to minutes
achieved through allosteric control and post translational modifications (PMT) of key enzymes in response to changes in metabolites or hormone signals
example: glycogen phosphorylase is sensitive to intracellular levels of AMP and phosphorylation in response to glucagon
how is metabolism controlled through long term regulation?
what do you need to know to understand transcriptional control
transcriptional control requires specific signals to be transduced to the cell nucleus where individual genes are gene network are targeted for regulation
what do metabolic transcriptional factors do
receive signals and bind DNA
CREB
ChREBP
SREBP-Ic
FoxO
CEBP
what are nuclear receptors and what do they do
what do metabolic coregulators do
what are the two types of coregulators and what do they do
PGC-1 alpha
what are regulators of PGC-I alpha
what are classic hormone ligands for nuclear receptors
what are the different superfamilies of nuclear receptors
what are metabolite ligands for nuclear receptors
what are orphan nuclear receptors
what are the functional domains of nuclear receptors?
what are the different nuclear receptors/DNA interactions?
how does ChIP sequencing work?
what are targets for ERRalpha?
nuclear receptors control all steps in the production of cellular energy from major substrates
they act as hubs that have ability to integrate multiple metabolic signals and control specific programs
-> coactivators can also do that