Unit 6 - Metabolic Integration Flashcards
what is the importance of the TCA? what are exceptions?
we can’t make glucose from FA
- OAA can be converted to glucose, but there is no NET conversion of ACoA to glucose
- exceptions: 3 C of glycerol backbone makes glucose in prolonged fasting (via lipolysis), and odd-chain FA make PCoA that becomes glucose
what is the major carbon source for anaplerotic (re-building stock) reactions?
pyruvate (from glucose, glucogenic AA, or cytosolic OAA via malate dehydrogenase and malic enzyme, but not significantly from fat)
what are the 5 major anaplerotic pathways?
- pyruvate carboxylase (make OAA)
- glu:a-KG transaminase and glu dehydrogenase (make a-KG)
- PCoA carboxylase and mmCoA epimerase + mmCoA mutase (make SCoA)
- AA –> fumarate
- asp:OAA transaminase (make OAA)
are catabolic and anabolic enzymes phosphorylated or dephosphorylated when active? what are examples?
catabolic: active when phosphorylated (AMP high, ATP low; release glucose)
- ex: phosphorylase kinase, glycogen phosphorylase, HSL
anabolic: inactive when phosphorylated (ATP high, AMP low; store glucose)
- ex: ACoA carboxylase, glycogen syntahse, HMG-CoA reductase
is epinephrine anabolic or catabolic?
catabolic; signals that E is needed right away
-stimulates breakdown, and inhibits synthesis of glycogen, fat, PRO
what is an example of futile cycle (waste ATP)? why does this happen?
adipocytes during fasting conditions
- 30-40% of NEFA made during lipolysis is re-esterified, instead of being released into circulation
- due to availability of glycerol-3-phosphate under fasting conditions
- acts as a brake on lipolysis, preventing too-rapid release of NEFA
- generates heat and contributes to hormonally controlled thermogenesis to regulate body mass
what happens in the fed state to:
- ACoA carboxylase
- HMG-CoA reductase
- HSL
- CREB (in fat cells)
- active, so more FA synthesis
- more active, so more cholesterol synthesis
- inactive, so less lipolysis, with unphosphorylated perilipin blocking access to fat droplets
- inactive, so decreased production of PEPCK (less gluconeogenesis)
what happens in the fasted state to:
- ACoA carboxylase
- HMG-CoA reductase
- HSL
- CREB (in fat cells)
- inactive, less FA synthesis
- less active, so less cholesterol synthesis
- active, so more lipolysis, with phosphorylated perilipin no longer blocking access to fat droplets
- active, so production of PEPCK for gluconeogenesis, TG resynthesis, and decreased NEFA
starvation
- insulin
- lipolysis
- KB production
- metabolic adjustments
- ketoacidosis
- low insulin/glucagon ratio, but always some insulin
- moderately high rate of lipolysis in fat cells
- moderate KB production by liver
- gradual/manageable adjustments (shift in use of KB as fuel, and excess is excreted by kidneys)
- no ketoacidosis (blood pH kept stable)
diabetes mellitus I
- insulin
- lipolysis
- KB production
- metabolic adjustments
- ketoacidosis
- NO circulating insulin
- uninhibited, max (runaway) lipolysis in fat cells
- max production of KB by liver, and production overwhelms removal
- -metabolism in extrahepatic tissues, kidney excretion, and exhalation of acetone
- metabolic ketoacidosis
how do epinephrine and glucocorticoid actions compare and contrast?
both generally encourage breakdown (counterregulatory hormones)
- E: stimulates glycogen breakdown, gluconeogenesis, and lipolysis
- G: stimulate lipolysis, AA release, and gluconeogenesis, BUT also stimulates glycogen synthesis
what is the Warburg effect?
aerobic glycolysis in cancer cells
- most ATP from glycolysis with release of lactate (pyruvate is used to make lactate, instead of TCA)
- cells take up lots of gln, which is converted to glu in mitochondria
what does inactivation of p53 do?
tumor suppressor gene
-promotes switch toward aerobic glycolysis, and away from use of TCA
