citric acid cycle Flashcards
TCA cycle - a biochemical hub of the intermediary metabolism:
- oxdizing carbons fuels for harvesting:
- it is ____ (e.g. catabolism and anabolism)
- source of precursors for
- takes place inside ____
- high energy electrons
- amphibolic
- biosynthesis
- mitochondria
other names of TCA cycle
Tricarboxylic acid cycle (TCA)
citric acid cycle
krebs cycle
precursor stage 1 of TCA
fats, polysaccharides, and proteins are reduced to fatty acids and glycerol, glucose and other sugars, and amino acids
precursor stage 2 of TCA
fatty acids and glycerols, glucose and other sugars, and amino acids are all converted to Acetyl CoA (common currency)
1 mol of NADH =
2.5 moles ATP
1 mol of FADH2 =
1.5 moles ATP
1 mol of GTP =
1 mol ATP
TCA cycle overview: oxidation of 2-carbon units to produce:
2 CO2 molecules
1 GTP
High energy electrons (3 NADH and 1 FADH2)
how is glucose converted into acetyl CoA?
glucose (6C) –oxidation–> 2 pryuvate (3C) –decarboxylation–> 2 Acetyl CoA (2C)
how are lipids converted into acetyl CoA?
TAG –> fatty acids –betaoxidation–> acetyl CoA (2C)
how are proteins converted to Acetyl CoA?
breakdown into various amino acids –> acetyl CoA
how is pyruvate converted to acetyl CoA?
- decarboxylation
- oxidation
- transfer acetyl group to CoA (by coupling with NAD+ –> NADH rxn)
aerobic glycolysis coupled with oxidative phosphorylation:
- pyruvate must enter:
- pyruvate utilizes:
- ______ catalyzes the decarboxylation of pyruvate
- the mitochondira
- mitochondrial pyruvate carrier (MPC)
- pyruvate dehydrogenase complex (PDC) or (PDH)
pyruvate dehydrogenase reaction:
- requires 3 enzymes:
- requires 5 coenzymes: catalytic cofactors and stoichiometric cofactors
- E1 (TPP), E2(Lipoic acid), E3(FAD)
2.
catalytic cofactors:
- thiamine pyrophosphate (TPP/Vitamin B1)
- lipoic acid
- FAD
stoichiometric cofactor:
- CoA
- NAD+
phosphorylated version of PDC/PDH is
inactive
dephosphorylated version of PDC/PDH is
active
overall reaction of pyruvate –> Acetyl CoA
pyruvate + NAD+ + CoA → Acetyl CoA + CO2 + NADH + H+
high [aceytl CoA] directly inhibits
E2
accumulation of ADP and pyruvate activates phosphatases which dephosphorylates ____
PDH/PDC (making it active)
increased levels of acetyl CoA will inhibit
PDH/PDC
the TCA cycle occurs under
aerobic conditions and procuces more energy from glucose than glycolysis
the TCA cycle takes place in the
mitochondria
what enzyme links glycolyis to the TCA cycle
pryuvate dehydrogenase (PDH/PDC)
first step of TCA cycle
4-carbon oxaloacetate + 2-carbon acetyl CoA +H2O → citrate
catalyzed by citrate synthase
step 2 of TCA cycle
citrate → isocitrate
catalyzed by aconitase
(because hydroxl group is not in proper location of oxidative decarboxylation)
step 3 of TCA cycle
isocitrate + NAD+ → a-ketoglutarate + NADH + H+ + CO2
catalyzed by isocitrate dehydrogenase
(rate-limiting step) (first of 4 redox rxns)
(NAD+ → NADH)
step 4 of TCA cycle
a-ketoglutarate + NAD+ + CoA → Succinyl CoA + NADH + H+ + CO2
via a-ketoglutarate dehydrogenase complex
step 5 of TCA cycle
succinyl CoA + GDP ⇔ Succinate + GTP + CoA
catalyzed by succinyl CoA synthetase
succinyl CoA contains a
high energy thioester bond
succinyl CoA synthetase is the only step that yields
a high energy phopho-transfer compount (ATP or GTP) (substrate level phosphorylation)
succinyl CoA synthetase isozymic forms:
- form that produces GTP is used in:
- form that produces ATP is used in:
- tissues that perform many anabolic reactions (liver)
- tissues that perofrm large amount of cellular respiration (skeletal and heart muscle)
step 6 of TCA cycle
succinate + FAD → Fumarate + FADH2
catalyzed by succinate dehydrogenase
(FADH2 is not released from the enzyme, but electrons are passed directly to Co-Q in the ETC
succinate dehydrogenase is located
in the inner mitochondrial membrane directly associated with ETC
step 7 of TCA cycle
fumarate → L-malate
catalyzed by fumarase
step 8 of TCA cycle
L-malate + NAD+ → Oxaloacetate + NADH + H+
catalyzed by malate dehydrogenase
high [acetyl CoA] directly inhibits
PDH/PDC complex subunit E2
(pyruvate + NAD+ → acetyl CoA + NADH → TCA cycle)
NADH inhibits
PDH/PDC complex subunit E3
(pyruvate + NAD+ → acetyl CoA + NADH → TCA cycle)
(ATP levels also inhibit PDH/PDC)
high [pyruvate] and high [ADP] activate
PDH/PDC activity
phosphatases are stimulated by
Ca2+ which increases to initiate muscle contraction
insulin can stimulate
fatty acid synthesis by activating phosphatases and increasing the conversion of pyruvate to acetyl CoA (a precursor for fatty acids)
activators of PDH/PDC
Ca2+, Mg2+ (via allosteric activation)
ADP, CoA, NAD+, pyruvate
insulin in adipose tissue, catecholamiens in cardiac muscle
inhibitors of PDH/PDC
acetyl CoA, NADH
acetyl CoA, ATP
arsenite
citrate synthase prevents
the wasteful hydrolysis of acetyl CoA
(first control site of TCA cycle)
oxaloacetate binds to citrate synthase first, then the enzyme
undergoes configurational changes to accept acetyl CoA
second control site of TCA cycle
isocitrate dehydrogenase
(allosterically stimulated by ADP) (NADH inhibits by directly displacing NAD+)
third control site of TCA cycle
a-ketoglutarate dehydrogenase
(this complex is similar to PDH/PDC)
(allosterically inhibited by its products- succinyl CoA and NADH)
buildup of citrate (due to regulation of isocitrate dehydrogenase) can be transported
to the cytosol and signal PFK to halt glycolysis
a-ketoglutarate that builds up from enzyme inhibition can be used for
synthesis of amino acids and purine bases
why is the TCA cycle anaplerotic
“fill up” rxns provide intermediates to replenish TCA cycle
2 major anaplerotic reactions
- degradation of amino acids
- carboxylation of pyruvate
- degradation of amino acids:
- Gln, Pro, His, Arg → replenishes a-ketoglutarate
- Thr, Met, Ile, Val → replenishes succinyl CoA
- Phe, Tyr, Asp → Fumurate
- carboxylation of pyruvate
* pyruvate (ATP + PC) → replenishes oxaloacetate
TCA cycle under fasting conditions
oxaloacetate → malate → gluconeogenesis → glucose
when energy needs are met, TCA cycle intermediates are
drawn for biosynthesis of other molecules
(citrate leaves mitochondria and forms fatty acids and sterols)
(a-ketoglutarate → glutamate → other amino acids → purines)
(succinyl CoA → porphyrins, heme, chlorophyll)
(oxaloacetate → asparate → other amino acids, purines/pyrimidines)
anaplerotic rxns are required during
states of low energy
