B2.043 Metabolism and its Regulation Pt. 2 Flashcards
how can metabolic plasticity be altered?
suppressed by over consumption of food
lost in type 1 diabetes
what mechanisms maintain caloric homeostasis in the fed state?
glycogenesis
glycolysis
lipogenesis
what mechanism maintain caloric homeostasis in the fasted state?
glycogenolysis gluconeogenesis lipolysis fatty acid oxidation ketogenesis
what are the 4 primary mechanisms for switching between fed and starved states?
substrate supply
allosteric effectors
covalent modification
induction repression of enzymes
what substrate is necessary for glycogenesis and lipogensis?
dietary glucose
what substrate is required for ketone body synthesis by the liver?
high serum fatty acid concentration
what substrates must be available for protein synthesis?
all 20 AAs
when can the brain use ketone bodies?
when blood concentration is high
about 48 hours starved
what are the 3 primary substrates involved in allosterically affecting the fed state?
glucose
fructose 2,6-P2
Malonyl-CoA
what enzymes does glucose allosterically affect?
inhibits glycogen phosphorylase
stimulates glycogen synthase
stimulates glucokinase
what enzymes does fructose 2,6-P2 allosterically affect?
inhibits fructose 1,6 bisphosphatase
stimulates phosphofructo-1-kinase (PFK1)
what enzyme does malonyl-CoA allosterically affect?
inhibits carnitine palmitoyl coA transferase 1 (CPT1)
what is CPT1?
rate limiting enzyme in oxidation of fatty acids
inhibited in fed state bc don’t want fats you just made to be broken down immediately
what substrate is required to transport long chain fatty acids into the mitochondrial matrix space?
carnitine
where does fatty acid oxidation occur?
mitochondrial matrix space
what are the 2 primary substrates involved in allosterically regulating the fasted state?
long chain acyl coA
acetyl coA
what enzyme does long chain acyl CoA allosterically affect?
inhibits acetyl CoA carboxylase to prevent fat production
what enzymes does acetyl CoA allosterically affect?
inhibits pyruvate dehydrogenase (makes pyruvate)
stimulates pyruvate carboxylase (makes oxaloacetate and eventually glucose)
what is the primary covalent modification that affects switching between fed and starved states?
phosphorylation
nonphosphorylated = fed
phosphorylated = starved
high insulin
low glucagon
low cAMP
low PKA activity
fed state
low insulin
high glucagon
high cAMP
high PKA
starved state
what are the rate limiting enzymes impacted by induction-repression pathways in the fed state?
glucokinase- glycolysis
G6P dehydrogenase -pentose phosphate
acetyl-CoA carboxylase- fatty acid synthesis
in the well fed state, what enzyme accounts for 10% of total liver enzymes?
fatty acid synthase
what transcription factors does insulin act on?
inhibits forkhead transcription factor
stimulates SREBP-1