LECTURE 33 - TRANSCRIPTIONAL CONTROL OF METABOLISM Flashcards
structure of HNF4 alpha (nuclear receptor)
central zone that incorporates surfaces from the two LBDs, the DBD of the upstream subunit and the hinge region of the downstream subunit
central zone is used by the different functional domains of HNF-4 alpha to communicate between each other
what can a mutation in HNF-4alpha cause?
MODY: maturity onset diabetes of the young
what are the activation and inhibition signals of HNF-4alpha?
what are mutations in HNF-4alpha that cause MODY 1?
characteristics of bile acids metabolism and their circulation?
most BAs are reabsorbed with 3-5grams being recycled multiple times each day
in the intestine BAs ar transported across the enterocytes lining into portal blood for circulation back to the hepatocytes sinusoids
BA production facilitates the excretion of lipids and steroids, but also aids in the absorption of dietary lipids and vitamins from the diet
how are bile acids synthesized?
what is the rate limiting step in cholesterol/BA metabolism?
what is the charge of BAs?
how is the CYP7alpha 1 gene expression controlled by nuclear receptors?
what is the cascade that controls CYP7alpha1 more precisely?
how is the Asbt gene controlled?
Asbt gene encodes ASBT, the major BA transport system in ileal enterocytes
deficiency in ASBT: significant BA
malabsorption disease
key concept: this pathway represents an example of the involvement of two signals: BAs and FGF15 regulating a cascade of transcription factors (FXR/RXR-> LRH/SHP-> LRH/RXR) with a switch between coactivators and corepressors resulting in the transcriptional control of BA synthesis and transport
what can too much high fructose corn syrup (HFCS) cause?
obesity, diabetes, MASLD, atherosclerosis, cardiometabolic and kidney diseases, cancer etc
why is HFCS harmful?
very harmful macronutrient
lipogenic sugar
distinct metabolism from glucose
impacts cellular signalling pathways, nutrient storage and insulin action
-> highest contributor is sugar sweetened beverages
what does a fructose rich diet do in humans?
rapidly increases intra abdominal adipose mass
the same diet increases de novo lipogenesis via generation of GA3P
how does fructose induce lipogenesis?
what metabolic pathways does fasting induce?
what is the transcription factor cascade that happens during fasting
what are patterns of the circadian system clock, some disregulations and the way to fix them?
the brain is the central clock and the other organs are the peripheral clocks
what is the master clock and how does it control peripheral clocks
how is circadian metabolism controlled by transcriptional control?
what are the core clock genes
what controls the core clock?
