TCA cycle Flashcards
Why does deficiency of thiamine/B1 cause beriberi - abnormalities in the peripheral nervous system, reflected in abnormal sensation and muscular weakness, and an enlarged heart?
Because these tissues rely heavily on oxidative metabolism (aerobic) to survive, and deficiency of thiamine disrupts the activity of pyruvate dehydrogenase (PDH) and alpha-ketogluarate in the citric acid cycle, because thiamine/B1 is a cofactors for both of these enzymes.
B1 Is also a cofactor for transketolase, which is in the PPP and allows for production of biomolecules.
When and how is PDH inactivated?
PDH is phosphorylated by a phosphatase into is inactive form when the cell/mitochondria is saturated with ATP or with the products of PDH reaction (AcetylCoA and NADH).
When and how is PDH activated?
PDH is dephosphorylated by a kinase into its active form when the cell/mitochondria is full of ADP and its substrates - pyruvate, NAD+.
At which steps is the TCA cycle regulated, and what are they limited by?
Reaction 3, catalyzed by isocitrate dehydrogenase (limited by availability of AcetylCoA) and reaction 4, catalyzed by alpha-ketogluarate (limited by NADH/NAD+ ratio and Ca2+ availability.
What cofactors do PDH and a-ketodehydrogenase require?
thiamine/B1, lipoid acid, coenzyme-A, FAD, NAD+
Where does the TCA occur?
inside the mitochondrial matrix
Which steps of TCA are irreversible and what reactions do they catalyze?
pyruvate dehydrogenase (pyruvate to AcetylCoA)
Citrate synthase (AcetylCoA to Citrate)
Isocitrate dehydrogenase (Isocitrate to a-ketoglutarate)
a-ketoglutarate dehydrogenase (a-ketoglutarate to Succinyl CoA)
If the cell is in high energy status with sufficient NADH, how does the TCA cycle stop producing NADH?
fatty acid biosynthesis is a major one.
Production of lactate from pyruvate is another major one.
Others would be glycogen synthesis in liver and muscle.
PPP in many cells until the NADPH stores are high
