TCA cycle Flashcards
4 sources of acetyl-CoA
pyruvate (glycolysis)
acetoacetate (ketone body)
acetate (ethanol)
palmitate (fatty acid)
how is acetyl-CoA formed from acetate?
acetyl-CoA synthase
what are the 2 types of acetyl-CoA synthase?
type1- liver, cytosol, used in FA synthesis
type2- heart/mm, mito matrix, feeds into TCA cycle
regulation of citrate synthase
inhibited: citrate
fates of excess citrate (3)
- inhibition of citrate synthase
- inhibition of phosphofructokinase-1
- conversion to fatty acid in cytosol by citrate lyase
MOA of aconitase
responsible for the conversion of citrate to isocitrate, contains iron-sulfur cluster, will shift OH from C3 to C2 so that first decarobylation can occur
describe the structure of a-ketoglutarate dehydrogenase
3 different enzyme complexes
describe E1 of a-ketoglutarate dehydrogenase
carries TPP and performs decarboxylation = CO2 leaves
describe E2 of a-ketoglutarate dehydrogenase
transfers 4C from a-ketoglutarate/TPP to CoASH with lipoic acid = succinyl-CoA forms
describe E3 of a-ketoglutarate dehydrogenase
transfers electrons from lipoid acid to FAD and then to NAD+ = NADH
what enzyme converts GTP to ATP?
nucleoside diphosphate kinase
MOA of succinate dehydrogenase
converts succinate to fumarate by removing double bond and transferring electrons to FAD to yield FADH2
what is unique about succinate dehydrogenase?
embedded in inner mito membrane, part of ETC, FADH2 is covalently attached via histidine, has iron-sulfur cluster that transfers electrons from FADH2 to coenzyme Q
fumarase deficiency
rare, AR, one of the only d/o of the TCA cycle enzymes that is not fatal “polygamists downs”
what is the high energy bond in acetyl-CoA and succinyl-CoA?
thioester bond with the acyl group
what makes the formation of acetyl-CoA favorable?
oxidative decarboxylation of pyruvate by pyruvate decarboxylase when pyruvate is acetly-coA source, other acetly-CoA sources use splitting of CC bonds
2 endergonic steps of TCA cycle
citrate- isocitrate (+1.5)
malate - oxaloacetate (+7.1)
still TCA cycle is -13.1 overall
alternative use for citrate
fatty acid synthesis
alternative use for a-ketoglutarate
amino acid synthesis, neurotransmitters (glutamate, GABA)
alternative use for succinyl-CoA
heme synthesis (contended with glycine to form d-aminolevulinic acid)
alternative use for malate
gluconeogenesis
alternative use for oxaloacetate
amino acid synthesis
what type of reactions will act to replenish TCA intermediates that have been extracted for other uses?
anapleurotic reactions= involve breakdown of amino acids to replenish all of the 4C intermediates that are removed
what is catapleurosis?
removing the TCA intemediates for biosynthesis (reverse of anepleurosis which is replenishing them)
what 3 aa are used to synthesize pyruvate?
serine, threonine, alanine
how can pyruvate be converted to oxaloacetate?
add CO2, ATP with pyruvate carboxylase and biotin = oxaloacetate
what 3 aa can be used to synthesize glutamate?
histidine, arginine, proline
how is glutamine converted to a-ketoglutarate?
direct transamination
what 3 aa can be used to form propionyl-CoA?
isoleucine, valine, methionine
what 2 aa can be used to form fumarate?
phenylalanine and tyrosine
action of citrate lyase
when citrate accumulates, citrate lyase converts citrate to acetyl-CoA and oxaloacetate hat can then be used for fatty acid synthesis
rate limiting step of TCA cycle
conversion of a-ketoglutarate to succinyl-CoA by a-ketoglutarate dehydrogenase
where is pyruvate dehydrogenase complex located?
mitochondrial matrix
describe the structure of the pyruvate dehydrogenase complex
3 catalytic units
2 regulatory units
3 catalytic units of pyruvate dehydrogenase complex
E1- dehydrogenase with TPP- removes CO2
E2- transacetylase with lipoamide- forms acetyl-CoA
E3- dehydrogenase with FAD- forms NADH
2 regulatory units of pyruvate dehydrogenase complex
1- PD kinase- phosphorylates serine and inhibits, + acetyl-CoA and NADH, - pyruvate
2- PD phosphatase- removes phosphate from serine to activate PD, + Ca
where is the m/c place to have a defect in PDHC?
E1
why is E3 of PDHC unique?
E3 gene is shared by a-ketoglutarate dehydrogenase
MOA of dichloroacetate
treatment for PDHC deficiency that works by inhibiting PD kinase, thereby increasing PDHC activity
what 2 enzymes will be affected by thiamine deficiency?
a-ketoglutarate dehydrogenase and pyruvate dehydrogenase bc they both need TPP as a cofactor in E1
how will arsenic and mercury affect PDHC and a-ketoglutarate dehydrogenase?
bind to sulfhydryl groups in the lipoamide and inactive it, treat with competitive inhibitor that 2,3-dimercaptopropanol (BAL)
