Glycogen, TCA Cycle and Mitochondria (Lecture 10) Flashcards
citric acid cycle
series of 8 enzymatic reactions that combine acetyl coa with oxaloacetate in order to generate CO2, NADH and FADH2 and regenerate the starting products of oxaloacetate
CAC is part of
aerobic glycolysis but does directly consume O2
how is CAC amphibolic
site of anabolism and catabolism
ANABOLISM:
CAC intermediates are the starting starting points of anabolic pathways (gluconeogenesis, FA synthesis, AA synthesis)
these are catapleyrotic reactions as for they deplete the pool of CAC intermediates
CATABOLISM:
CAC intermediates are the end point of catabolic pathways . the aerobic catabolism of carbohydrates, lipids and amino acids merge into the CAC (oxaloacetate from pyruvate carboxylase, AA degradation)
these are anapleurotic reaction, as for they replenish the depleted CAC intermediates
3 main functions of CAC
produce reducing equivalents in the for of NADH and FADH2 (these are e- carrying molecules that can donate their e- to the ETC)
produce intermediates for the biosynthesis of:
citrate –> fatty acids
alpha keto glutarate –> amino acids
removed carbon form the metabolite
does CAC generate energy
yes via reducing equivalents and 1 GTP is also formed
overall reaction of CAC shows that it generates
3 NADH FADH2 GTP CO2 CoA
what confers directionality
3 committing steps:
citrate synthase (acetyl coa–> citrate)
isocitrate dehydrogenase (isocitrate –> alpha KG)
alpha-KG dehydrogenase (alpha KG –> succinyl-coa)
citrate synthase
oxaloacetate + acetyl coa –> citrate
condensation from a 2C (acetyl coa) and 4C (ox.) to generate a 6C
the thirster bind in acetyl coa is used to synthesize citrate
there is a negative free energy, thus making is irreversible
aconitase
citrate to isocitrate
reversible isomérisation
isocitrate dehydrogenase
isocitrate + NAD+ –> alpha KG + CO2 + NADH + H+
dehydrogenase reaction generates NADH and decarboxylation releases a carbon via CO2
CO2 is derived from oxaloacetate
alpha KG dehydrogenase
alpha KG + CoA + NAD+ –> succinylcholine CoA + CO2 + NADH + H+
oxidative decarboxyaltion genres NADH and CO2, this provides the energy to generate the high energy intermediate: SUCCINYL COA
multi enzyme complex
succinyl coa synthase
succinyl coa + GDP + Pi –> succinate + GTP
uses energy of succcinyl coa to generate gtp
succinate dehydrogenase
succiante E-FAD –> E-FADH2 + fumarate
covalently bound to FAD
the succinate DH-FAD is oxidized to form succinate DH- FADH2. FAD is then rested by funnelling its e- into the ETC
where is FADH2 donated
the e- from FADH2 from succinate DH is donated to complex II to the ETC
fumarase
fumarate + H2O –> malate
malate dehydrogenase
malate + NAD= –> oxaloacetate + NADH + H+
final step of CAC
although its endergonic, the true delta G is 0 because :
- in vivo [malate]»> [oxalo]
the next reaction involving citrate synthase is highly exergonic, which allows the formation of citrate to be exergonic even at low [oxalo] (due to acetyl coats energy supplies by the thirster bond)
this implies that there is a coupling of both reactions to help CAC move forward
CAC balance sheet
3 NADH x 2.5 = 7.5 ATP
FADH2 x 1.5 = 1.5 ATP
GTP =ATP
total of 10 ATP
total of CAC, glycolysis and PDC = (10x2 bc 2 acetyl coa/glu) + 7 + (2.5 x 2 pyruvate/glu) = 32 ATP/glucose
regulation of citrate synthase
substrate availability of acetyl coa and oxaloacetate
in vivo acetyl coa and oxaloacetate do not saturate citrate synthase
the amount of acetyl coa is derived by PDC reaction
product inhibition via citrate the product of the reaction acts as a competitive inhibitor of oxaloacetate binding to the citrate synthase
competitive feedback, succinyl coa competes with acetyl coa to inhibit
allosteric inhibition via NADH (noty a product)
allosteric activation (ADP)
regulation of isocitrate dehydrogenase
product inhibition via NADH
allosteric activation via ADP and Ca2+
when isocitrate DH is inhibited,, the amount of isocitrate will build and since the aconite reaction is reversible, citrate will be regenerated and released in the cytoplasm
citrate in the cytoplasm activates acetyl coa carboxylase , thus activating FA synthesis and this inhibits PFK thus inhibiting glycolysis
surplus of citrate indicates
high energy
regulation of alpha keto glutarate DH
product inhibition via NADH and succinyl coa
allosteric activation via Ca2+
what does citrate also inhibit
PFK1 allosterically, which inhibits the conversion of F6P –> F1,6BP
the committing step to glucose metabolism
PDC is switched off when
energy charge is high, product inhibition via acetyl coa and NADH.
this activates PDH kinase
regulation of pyruvate carboxylase
one molecule of oxaloacetate required to run CAC
accumulation of acetyl via indicates that there e is a need for oxaloacetate in order to run CAC
excess pyruvate is converted into
oxaloacetate when carrboxylated
name the anabolic/catabolic processes of pyruvate
catabolic= synthesis of acetyl coa
anabolic = synthesis of oxaloacetate
