the citric acid cycle

what is the CAC also known as

the tricarboxylic acid cycle or Krebs cycle

What are the membranes of the mitochondria

the inner and outer membranes

what are cristae

they are extensions of the inner membrane, layers of sac-like structures that fill the interior of the mitochondria and are connected to the inner membrane by a short tube

where is the mitochondria matrix

it is inside the inner membrane

when is pyruvate produced

it is produced during glycolysis

what is the oxidation process of pyruvate

a carboxyl group is removed from pyruvate, releasing carbon dioxide

NAD+ is reduced to NADH

an acetyl group is transferred to coenzyme A, resulting in acetyl CoA

what is the pyruvate processing net reaction

oxidative decarboxylation of pyruvate and the first carbons of glucose to be fully oxidized to become CO2

What is the conversion of pyruvate to acetyl-CoA regulated by

it is regulated by feedback inhibition, it will stop when the products of PDC (NADH and acetyl-CoA) are abundant and the PDH is phosphorylated and inhibited through shape change

What is the conversion of pyruvate to acetyl-CoA catalyzed by

it is catalyzed by the pyruvate dehydrogenase complex (PDC)

what are the 5 coenzymes that are involved in the pyruvate dehydrogenase complex

thiamine pyrophosphate (TPP), lipoate (lipoid acid), FAD, NAD+, and coenzyme A-SH (CoA-SH)

What does E1 Pyruvate dehydrogenase require and what are the first two steps of oxidative decarboxylation of pyruvate

it requires TPP

step 1: decarboxylation of pyruvate and release of CO2

step 2: oxidation and transfer to lipoamide, the electrons reduce lipoamide and form a thioester

what is a thioester

it is a lipoamide attached to E2

What is step 3, 4, and 5 of the oxidative decarboxylation of pyruvate, with the involvement of E2 dihydrolipoyl transacetylase

step 3: it is transfer of acetyl group to Coenzyme A: acetyl coA

step 4: deoxidation of the reduced lipoamide cofactor (dihydrolipoamide) via electron transfer to FAD

step 5: regeneration of the oxidized FAD cofactor which forms NADH (product 2)

what are coenzymes

they are not a permanent part of the enzymes structure, they associate, fulfill a function and dissociate

what is the function of CoA

its only function is to accept and carry acetyl groups they will carry the remaining carbon from glucose to the citric acid cycle to be further oxidized.

when is CoA-SH removed

it is removed in the first part of the citric acid cycle

what is the reactant that enters the citric acid cycle from glycolysis

Acetyl-CoA is the reactant

What feeds into the citric acid cycle

multiple metabolic pathways in the cell will feed molecules into it and multiple intermediated from the citric acid cycle can be used as reactants in other metabolic pathways

what does it mean for the citric acid cycle to be amphibolic

it means that it involves both catabolism and anabolism

what are the sequence of events in the citric acid cycle

step 1: C-C bond formation between acetate (2C) and oxaloacetate (4C) to make citrate (6C)

step 2: isomerization via dehydration/rehydration

steps 3-4: Oxidative decarboxylations to give 2 NADH

step 5: substrate-level phosphorylation to give GTP

step 6: dehydrogenation to give FADH2

step 7: hydration

step 8: Dehydrogenation to give NADH

what are characteristics of step 1, C-C bond formation by condensation of acetyl-CoA and oxaloacetate

condensation of acetyl-CoA and oxaloacetate,

the only reaction with a C-C bond,

rate limiting step of the CAC,

activity is largely dependent on [oxaloacetate],

it is highly thermodynamically favorable/irreversible which is regulated by substate availability and product inhibition

what are the characteristics for step 2, isomerization by dehydration/rehydration

elimination of H2O from citrate gives a cis C=C bond,

addition of H2O to cis aconite is stereospecific,

thermodynamically unfavorable/reversible so the product concentration is kept low to pull the reaction forward

what is citrate

it is a tertiary alcohol and a poor substrate for oxidation

what is isocitrate

it is a secondary alcohol and a good substrate for oxidation

what are the characteristics of step 3, oxidative decarboxylation by isocitrate dehydrogenase

isocitrate loses one carbon by oxidative decarboxylation which will release CO2 and produce one NADH,

the isozymes are specific for NADP (cytosolic) or NAD+ (mitochondrial)

it is highly favorable/irreversible and regulated by [ATP]

what are the characteristics of step 4, oxidative decarboxylation by alpha ketoglutarate dehydrogenase

it is another oxidative decarboxylation that produces NADH and CO2,

it will produce succinyl-CoA which is similar in structure to Acetyl-CoA

its complex is similar to pyruvate dehydrogenase because they will have the same coenzymes with identical mechanisms but different active sites to accommodate different sized substrates.

it is highly thermodynamically favorable/irreversible which is regulated by product inhibition

What step has the last oxidative decarboxylation

step 4, it will produce the net full oxidation of all carbons of glucose of initial glucose molecule which entered glycolysis

what is succinyl-CoA

it is another higher-energy thioester bond, like acetylcoA

what are the characteristics of step 5, generation of GTP through thioester: substrate-level phosphorylation by succinyl-CoA synthetase

it is substrate level phosphorylationand the energy of thioester allows for incorporation of inorganic phosphate.

it goes through a phosphor-enzyme intermediate

it is slightly thermodynamically favorable/reversible due to the product concentration being kept low to pull the reaction forward

what are the characteristics of step 6, oxidation of an alkane to alkene by succinate dehydrogenase

succinate dehydrogenase is bound to mitochondria inner membrane and acts like complex 2 in the ETC.

the oxidation of the alkane to alkene requires FADH2 because oxidation potential of carbon-hydrogen bond is too low for production of NADH

FAD is covalently bound, which is unusual

it is near equilibrium/reversible due to the product concentration being kept low to pull the reaction forward

what are the characteristics of step 7, hydration across a double bond: fumarase

it is stereospecific so the addition of water is always trans and forms L-malate, OH- adds to fumarate then H+ adds to the carbanion, and it cannot distinguish between inner carbons

it is slightly thermodynamically favorable/reversible due to the product concentration being kept low to pull the reaction forward

what are the characteristics of step 8, oxidation of alcohol to a ketone and regeneration of oxaloacetate by malate dehydrogenase

final step

regenerates oxaloacetate for citrate synthase which produces NADH

highly thermodynamically unfavorable/reversible because the oxaloacetate concentration kept VERY low by citrate synthase which pulls the reaction forward

how many turns of the citric acid cycle occur for each glucose molecule oxidized by glycolysis

there are 2 turns for each oxidized glucose

what is the net oxidation of the CAC

it has a net oxidation of 2 carbons to CO2

what does the energy captured during the CAC transfer to

it transfers to NADH and FADH2

what does the CAC generate

it generates 1 GTP which can be converted to ATP

what are the intermediates of the CAC drawn off as

they are drawn off as precursors in many biosynthetic pathways and are amphibolic

what does anaplerotic mean

it means to fill up

what are the 4 anaplerotic reactions of the CAC

pyruvate to oxaloacetate through pyruvate carboxylase

phosphoenolpyruvate to oxaloacetate through PEP carboxylase or PEP carboxykinase

pyruvate to malate through malic enzyme

What are anaplerotic reactions

they are intermediates in the citric acid cycle that can be used in biosynthetic pathways (removed from cycle) and they must replenish the intermediates in order for the cycle and central metabolic pathway to continue

what are the 4 carbon intermediates formed by

they are formed by carboxylation of 3 carbon precursors

what converts pyruvate into acetyl CoA

a large multiunit subenzyme, pyruvate dehydrogenase complex

what does the citric acid cycle

it is an important catabolic process that makes GTP and reduced cofactors that could yield ATP and it plays an important anabolic roles in the cell

what are the two chemical mechanisms that change pyruvate to acetyl-CoA in the pyruvate dehydrogenase complex

dehydrogenation and decarboxylation

how many electrons are transferred to electron carriers after one turn of the citric acid cycle

there are 8 transferred to electron carriers after one cycle

how many NADH molecules are generates from the complete oxidation of one glucose

there are 10 produced

what enzymes catalyze an irreversible reaction in TCA cycle

citrate synthase: catalyzes condensation of Acetyl-CoA and ocaloacetate to form citrate

isocitrate dehydrogenase: converts isocitrate to alpha ketoglutarate releasing CO2 and generating NADH

alpha ketoglutarate dehydrogenase: converts alpha ketoglutarate to succinylcholine-CoA release CO2 and generating NADH