MCT Block 3 Part 1
major substrate sources that enter TCA cycle correct answers carbohydrates (glucose)
fatty acids
ketone bodies
alanine
ethanol
what enzyme converts pyruvate to acetyl-coA correct answers pyruvate
dehydrogenase complex (PDC or PDH)
features of pdc correct answers -large multienzyme complex
-three types of protein subunits
-utilizes five cofactors
-regulated
what chemistry is used to convert a-ketoglutarate to succinyl-coA correct answers
same as PDH
E3 subunit is same protein that serves as E3 subunit of akg dh complex
3 enzymes of pdc correct answers -pyruvate decarboxylase (E1)
-dihydrolipoyl transacetylase(E2)
-dihydrolipoyl dehydrogenase (E3)
pdc 5 cofactors correct answers -thiamine pyrophosphate
-lipoic acid
-coenzyme A
-FAD
-NAD+
(Tender Loving Care For Nancy)
E1 reaction correct answers releases CO2 and attaches remaining carbons to
Thiamine-PPi
E2 reaction correct answers first moves carbon chain from TPP to lipoic acid, then
carbons are transferred to coenzyme A
E3 reaction correct answers uses tightly bound FAD to oxidize the lipoic acid back to
disulfide form, then transfers protons and electrons from FADH2 to NAD+ to form NADH
and H+ that are released from complex
,transcriptional regulation of pdc correct answers amount of enzyme reduced during a
fast and is increased by insulin when fed
allosteric regulation of pdc correct answers regulated by energy state of cell and by
substrates and products:
Inhibitory: nadh, acetyl-coA
activators: nad+, CoASH
pdc regulation by covalent modification (phosphorylation) correct answers -pyruvate
dehydrogenase kinase (complex associated, allosterically regulated)
-pyruvate dehydrongenase phosphatase (complex associated, regulated by calcium)
-principle form of regulation
-phosphorylated=inactive!
pdc kinase correct answers inhibited by adp & pyruvate
-pdc on (ATP/ADP)
activated by NADH and acetyl coA (PDC off)
pdc kinase occurs as correct answers tissue specific forms
where does phosphorylation of pdc occur? correct answers on pyruvate decarboxylase
subunit (E1)
where are 7/8 TCA enzymes located correct answers mitochondrial matrix
where is succinate dehydrogenase located correct answers inner mitochondrial
membrane
what does tca pathway accomplish correct answers complete oxidation of acetyl
groups to CO2
tca cycle yields energy as correct answers NADH, FADH2, GTP
TCA cycle is major source of correct answers reduced coenzymes for electron
transport and oxidative atp formation
what pathways besides tca cycle contribute reduced coenzymes for electron transport
and oxidative atp formation correct answers fatty acid oxidation
glycolysis
what are the energy yielding steps of tca cycle correct answers isocitrate dh
a-ketoglutarate dh
succinate thiokinase
succinate dh
malate dh
,what does isocitrate dh yield correct answers nadh + h+
what does a-ketoglutarate yield correct answers nadh + h+
what does succinate thiokinase yield correct answers gtp
what does succinate dh yield correct answers fadh2
what does malate dh yield correct answers nadh + h+
what is the energy yield in et/atp synthase correct answers 10 atp
E1 of a-ketoglutarate dh correct answers results in decarboxylation of a-ketoglutarate,
with transfer of other four carbons to tpp
what enzyme is complex II correct answers succinate dehydrogenase
in inner mitochondrial membrane, feeds electrons into electron transport pathway for atp
production
what reflects the energy status of a cell or energy charge correct answers ratio of
atp/adp and nadh/nad+
what kind of regulator is NADH correct answers major negative regulator
what kind of regulator is adp correct answers positive allosteric regulator
how is citrate synthase primarily regulated correct answers by availability of
oxaloacetate
how are the three enzymes that produce NADH regulated correct answers inhibited by
nadh
what is the rate limiting step of tca cycle correct answers isocitrate dehydrogenase
(allosteric enzyme)
how is a-ketoglutarate dh regulated correct answers inhibited by nadh (but not a
allosteric enzyme)
calcium activates what two tca enzymes in muscle correct answers isocitrate dh and a-
ketoglutarate dh
tca rate is dictated by correct answers rate of nadh use by electron transport, which is
regulated by need for atp
, anaplerotic reactions correct answers replaces lost intermediates to maintain pathway
when intermediates are removed, or speed it up for more energy production
what is the primary anaplerotic pathway for tca cycle correct answers pyruvate
carboxylase
(in tissues other than liver, propionyl-coA pathway is second most important)
what is a major source of added tca intermediaes in liver correct answers a-
ketoglutarate produced by transamination or by oxidative deamination of glutamate
hyperpyruvic acidemia correct answers -most often from defective E1 within pdc
complex (x linked pdhad gene)
-lots of hetero females have symptoms
-mutations can be in 1/5 other subunits or regulatory proteins
-low percent will respond favorably to large doses of B1
metaolic presenation of hyperpyruvic acidemia correct answers severe lactic acidosis in
newborn period that is fatal
neurologic presentation of hyperpyruvic acidemia correct answers hypotonic, lethargic,
mental retardation, seizures, minimal metabolic issues but cns structural abnormalities
thiamine deficiency correct answers impaired pdc leads to increased conversion
(reduction) of pyruvate to lactate
-lactic acidosis
-hypoglycemia from impaired gluconeogenesis
how does hepatic EtOH metabolism heighten lactic acidosis correct answers high nadh
drives ldh in lactate direction
isocitrate dh 1 correct answers cytosolic
-important roles in lipid metabolism and insulin release
isocitrate dh 2 correct answers mitochondria
-major role in controlling mitochondrial redox balance and mitigating cellular oxidative
damage
idh1 and 2 mutations correct answers -frequently mutated in gliomas and myeloid
leukemia
-r132 in idh1 or idh2 (r172)
-mutation of active site arginine blocks final oxidation, changing final product from a-
ketoglutarate to 2-hydroxyglutarate which accumulates to high levels
2-hydroxyglutarate correct answers strong inhibitor of a-ketoglutarate dependent
dioxygenases
-high levels results in epigenetic changes
major substrate sources that enter TCA cycle correct answers carbohydrates (glucose)
fatty acids
ketone bodies
alanine
ethanol
what enzyme converts pyruvate to acetyl-coA correct answers pyruvate
dehydrogenase complex (PDC or PDH)
features of pdc correct answers -large multienzyme complex
-three types of protein subunits
-utilizes five cofactors
-regulated
what chemistry is used to convert a-ketoglutarate to succinyl-coA correct answers
same as PDH
E3 subunit is same protein that serves as E3 subunit of akg dh complex
3 enzymes of pdc correct answers -pyruvate decarboxylase (E1)
-dihydrolipoyl transacetylase(E2)
-dihydrolipoyl dehydrogenase (E3)
pdc 5 cofactors correct answers -thiamine pyrophosphate
-lipoic acid
-coenzyme A
-FAD
-NAD+
(Tender Loving Care For Nancy)
E1 reaction correct answers releases CO2 and attaches remaining carbons to
Thiamine-PPi
E2 reaction correct answers first moves carbon chain from TPP to lipoic acid, then
carbons are transferred to coenzyme A
E3 reaction correct answers uses tightly bound FAD to oxidize the lipoic acid back to
disulfide form, then transfers protons and electrons from FADH2 to NAD+ to form NADH
and H+ that are released from complex
,transcriptional regulation of pdc correct answers amount of enzyme reduced during a
fast and is increased by insulin when fed
allosteric regulation of pdc correct answers regulated by energy state of cell and by
substrates and products:
Inhibitory: nadh, acetyl-coA
activators: nad+, CoASH
pdc regulation by covalent modification (phosphorylation) correct answers -pyruvate
dehydrogenase kinase (complex associated, allosterically regulated)
-pyruvate dehydrongenase phosphatase (complex associated, regulated by calcium)
-principle form of regulation
-phosphorylated=inactive!
pdc kinase correct answers inhibited by adp & pyruvate
-pdc on (ATP/ADP)
activated by NADH and acetyl coA (PDC off)
pdc kinase occurs as correct answers tissue specific forms
where does phosphorylation of pdc occur? correct answers on pyruvate decarboxylase
subunit (E1)
where are 7/8 TCA enzymes located correct answers mitochondrial matrix
where is succinate dehydrogenase located correct answers inner mitochondrial
membrane
what does tca pathway accomplish correct answers complete oxidation of acetyl
groups to CO2
tca cycle yields energy as correct answers NADH, FADH2, GTP
TCA cycle is major source of correct answers reduced coenzymes for electron
transport and oxidative atp formation
what pathways besides tca cycle contribute reduced coenzymes for electron transport
and oxidative atp formation correct answers fatty acid oxidation
glycolysis
what are the energy yielding steps of tca cycle correct answers isocitrate dh
a-ketoglutarate dh
succinate thiokinase
succinate dh
malate dh
,what does isocitrate dh yield correct answers nadh + h+
what does a-ketoglutarate yield correct answers nadh + h+
what does succinate thiokinase yield correct answers gtp
what does succinate dh yield correct answers fadh2
what does malate dh yield correct answers nadh + h+
what is the energy yield in et/atp synthase correct answers 10 atp
E1 of a-ketoglutarate dh correct answers results in decarboxylation of a-ketoglutarate,
with transfer of other four carbons to tpp
what enzyme is complex II correct answers succinate dehydrogenase
in inner mitochondrial membrane, feeds electrons into electron transport pathway for atp
production
what reflects the energy status of a cell or energy charge correct answers ratio of
atp/adp and nadh/nad+
what kind of regulator is NADH correct answers major negative regulator
what kind of regulator is adp correct answers positive allosteric regulator
how is citrate synthase primarily regulated correct answers by availability of
oxaloacetate
how are the three enzymes that produce NADH regulated correct answers inhibited by
nadh
what is the rate limiting step of tca cycle correct answers isocitrate dehydrogenase
(allosteric enzyme)
how is a-ketoglutarate dh regulated correct answers inhibited by nadh (but not a
allosteric enzyme)
calcium activates what two tca enzymes in muscle correct answers isocitrate dh and a-
ketoglutarate dh
tca rate is dictated by correct answers rate of nadh use by electron transport, which is
regulated by need for atp
, anaplerotic reactions correct answers replaces lost intermediates to maintain pathway
when intermediates are removed, or speed it up for more energy production
what is the primary anaplerotic pathway for tca cycle correct answers pyruvate
carboxylase
(in tissues other than liver, propionyl-coA pathway is second most important)
what is a major source of added tca intermediaes in liver correct answers a-
ketoglutarate produced by transamination or by oxidative deamination of glutamate
hyperpyruvic acidemia correct answers -most often from defective E1 within pdc
complex (x linked pdhad gene)
-lots of hetero females have symptoms
-mutations can be in 1/5 other subunits or regulatory proteins
-low percent will respond favorably to large doses of B1
metaolic presenation of hyperpyruvic acidemia correct answers severe lactic acidosis in
newborn period that is fatal
neurologic presentation of hyperpyruvic acidemia correct answers hypotonic, lethargic,
mental retardation, seizures, minimal metabolic issues but cns structural abnormalities
thiamine deficiency correct answers impaired pdc leads to increased conversion
(reduction) of pyruvate to lactate
-lactic acidosis
-hypoglycemia from impaired gluconeogenesis
how does hepatic EtOH metabolism heighten lactic acidosis correct answers high nadh
drives ldh in lactate direction
isocitrate dh 1 correct answers cytosolic
-important roles in lipid metabolism and insulin release
isocitrate dh 2 correct answers mitochondria
-major role in controlling mitochondrial redox balance and mitigating cellular oxidative
damage
idh1 and 2 mutations correct answers -frequently mutated in gliomas and myeloid
leukemia
-r132 in idh1 or idh2 (r172)
-mutation of active site arginine blocks final oxidation, changing final product from a-
ketoglutarate to 2-hydroxyglutarate which accumulates to high levels
2-hydroxyglutarate correct answers strong inhibitor of a-ketoglutarate dependent
dioxygenases
-high levels results in epigenetic changes
