The TCA/Krebs/citric acid cycle

under which conditions, pyruvate is oxidized to acetyl-CoA and NAD+ is regenerated in the mitochondria

aerobic

TCA

acetyl-CoA enters the which cycle

An what group is transferred to Coenzyme A to generate acetyl CoA

acetyl

The two-carbon acetyl unit enters the TCA cycle, which processes it to make how many molecules of CO2 while generating high-energy electrons that can be used to make ATP

2

pyruvate dehydrogenase complex

a mitochondrial matrix enzyme, oxidatively decarboxylates pyruvate to form acetyl CoA

pyruvate dehydrogenase complex, This irreversible step commits the carbon atoms of the glucose to being what in the TCA cycle to make energy (or to being used to make fatty acids)

oxidized

pyruvate

occurs in the cytoplasm

import of what
into the mitochondria

occurs in the mitochondria

There are large pores in the mitochondrial which membrane and pyruvate can pass
through them, but getting through the inner mitochondrial membrane into the
mitochondrial matrix requires active transport (requires energy) via the mitochondrial
pyruvate carrier

outer

The pyruvate dehydrogenase (PDH) complex makes acetyl CoA by what decarboxylation

oxidative

The pyruvate dehydrogenase (PDH) complex = an irreversible oxidation process in which the carboxyl group is removed, forming what and reducing NAD+ to NADH

CO2

pyruvate

The synthesis of acetyl CoA from what consists of three
steps: a decarboxylation, an oxidation, and the transfer of
acetyl to CoA

The pyruvate dehydrogenase complex
consists of how many enzymes each with its own active site

three

The pyruvate dehydrogenase complex
consists of three enzymes each with its own active site
- two carry out the reaction

E1, E2

The pyruvate dehydrogenase complex
consists of three enzymes each with its own active site
- one regenerates the system

E3

The pyruvate dehydrogenase complex
consists of three enzymes each with its own active site
- how many coenzymes are necessary

5

coenzyme

Decarboxylation:
– Pyruvate dehydrogenase (E1) combines pyruvate with the what thiamine pyrophosphate (TPP; derived from vitamin B1) to form an TPP-hydroxyethyl intermediate and liberate a CO2

lipoamide

Oxidation:
– Pyruvate dehydrogenase (E1) then oxidizes the hydroxyethyl group to an acetyl group and transfers it to the coenzyme what.
The disulfide of what is reduced. The reaction yields acetyl–lipoamide, with an energy-rich thioester bond

Lipoamide, a coenzyme, is formed by the attachment
of the vitamin lipoic acid to a what residue

lysine

Formation of acetyl CoA:
– Dihydrolipoyl transacetylase (E2) catalyzes the transfer of
the acetyl group from acetyl–lipoamide to coenzyme A to form what

acetyl CoA

Regeneration:
- dihydrolipoamide dehydrogenase (E3) does what dihydrolipoamide to
lipoamide so it can be used again

oxidizes

NADH

. Regeneration:
An FAD is reduced to FADH2 in the process. These electrons are then passed to NAD+ reducing it to what

Pyruvate Dehydrogenase Forms Acetyl Coenzyme A from Pyruvate

This occurs twice per glucose, so how many NADH are formed by this
enzyme complex per glucose that enters glycolysis

2

Substrate channeling

the passage of intermediates from one enzyme directly to another enzyme without release

Conversion of pyruvate to acetyl CoA is a what step before TCA
cycle and oxidative phosphorylation - don’t do it unless energy is needed

irreversible

PDH activity is turned off when:
- ATP/ADP and NADH/NAD+ ratios are what

high

fuel

PDH activity is turned off when:
- ample fatty acids and acetyl-CoA are available as what

PDH activity is turned on when:
- energy demands are high resulting in a what ATP/ADP ratio

low

PDH activity is turned on when:
- what cycle intermediates are needed to make other molecules

TCA

phosphorylation

PDH kinase = inhibits the PDH complex by what

PDH kinase = inhibits the PDH complex by phosphorylation
- allosterically what by products of the PDH complex (ATP, NADH, acetyl CoA)

activated

PDH kinase = inhibits the PDH complex by phosphorylation
- allosterically what by substrates of the PDH complex (ADP, NAD+, pyruvate)

inhibited

PDH phosphatase = reverses the what by PDH kinase

inhibition

The Disruption of Pyruvate Metabolism Is the Cause of what

Beriberi

what deficiency results in insufficient pyruvate dehydrogenase activity because what is needed to make TPP

Thiamine

Insufficient pyruvate what activity causes the neuromuscular disease beriberi - symptoms include weakness, pain, and loss of feeling in the limbs, difficulty walking, mental confusion, and speech difficulties

dehydrogenase

The citric acid cycle what the acetyl fragment of acetyl CoA to CO2

oxidizes

In the process of oxidation, what-energy electrons are captured in the form of NADH and FADH

high

Metabolism

What breaks down other biomolecules into acetyl-CoA which enter the TCA cycle

metabolism

The TCA cycle is a hub for what

A key function of the citric acid cycle is to harvest high-energy electrons from what fuels

carbon

Two Stages of the Citric Acid Cycle
In the which stage, two carbons are introduced into the cycle when an acetyl group (2C) undergoes condensation with oxaloacetate (4C) to make citrate (6C)

first

citrate undergoes how many oxidative decarboxylations, generating two molecules of CO2 (1C) and a 4C compound

2

Two Stages of the Citric Acid Cycle
In the what stage, oxaloacetate is regenerated to be use again

second

Two Stages of the Citric Acid Cycle

Both stages generate high-energy electrons (carried by NADH and FADH2) that are used later to power the synthesis of what in oxidative phosphorylation

ATP

In one ’turn’ of the cycle, citrate formed from one acetyl-CoA and oxaloacetate is oxidized to yield:
? CO2
? NADH
? FADH2
? GTP or ATP

2, 3, 1, 1

Two Stages of the Citric Acid Cycle
In the first stage, two carbons are introduced into the cycle by condensation of an acetyl group with a four-carbon compound, what

oxaloacetate

The six-carbon compound citrate molecule formed undergoes two oxidative decarboxylations, generating how many molecules of CO2.

2

synthase

Citrate what catalyzes the condensation of acetyl CoA with oxaloacetate to form citrate (via a citryl CoA intermediate)

PDH

CoA is regenerated to be reused by what

isocitrate

Aconitase catalyzes the formation of what from citrate via an intermediate

Aconitase catalyzes the formation of isocitrate from citrate via an
intermediate
- what reaction, but flux through pathway pulls reaction forward

endergonic

Isocitrate dehydrogenase catalyzes the oxidative decarboxylation of isocitrate, forming α-ketoglutarate and CO2 and capturing what-energy electrons as NADH

high

α-ketoglutarate dehydrogenase complex catalyzes the oxidative
decarboxylation of α-ketoglutarate to what-CoA and CO2

succinyl

α-ketoglutarate dehydrogenase complex catalyzes the oxidative
decarboxylation of α-ketoglutarate to succinyl-CoA and CO2
- what-energy electrons captured as NADH

high

Two dehydrogenases do oxidative carboxylation
- ? CO2 are formed
- ? NADH are formed

2, 2

oxaloacetate

Two Stages of the Citric Acid Cycle
In the second stage, what is regenerated

succinate

succinyl-CoA synthetase catalyzes the breakage of the thioester bond of
succinyl-CoA to form what

succinyl-CoA synthetase catalyzes the breakage of the thioester bond of succinyl-CoA to form succinate
- energy released drives the synthesis of a what bond in GTP or ATP

phosphate

Reaction Mechanism of Succinyl CoA Synthetase

The reaction involves formation of succinyl phosphate, a high- phosphoryl-transfer-potential compound, which can donate a phosphate to ADP in a what-level phosphorylation to form ATP

substrate

nucleoside diphosphate

what kinase = catalyzes the reversible interconversion of GTP and ATP

flavoprotein

succinate dehydrogenase = what that catalyzes the reversible
oxidation of succinate to fumarate and reduction of FAD to FADH

succinate dehydrogenase = flavoprotein that catalyzes the reversible oxidation of succinate to fumarate and reduction of FAD to FADH2
- integral protein of the mitochondrial what membrane in eukaryotes

inner

fumarase catalyzes the reversible what of fumarate to L-malat

hydration

?-malate dehydrogenase catalyzes the oxidation of malate to oxaloacetate, coupled to the reduction of NAD+ to NADH

L

A dehydrogenase forms a what

FADH2

Another dehydrogenase forms a third what

NADH

phosphorylation

An ATP or GTP is made by substrate-level what

The electrons from each NADH will generate how many ATP when used to reduce oxygen in the electron-transport chain

2.5

The electrons from one FADH2 will generate how many ATP with the reduction of oxygen in the electron-transport chain

1.5

the citric acid cycle directly generates how many ATP per cycle

1

one glucose will make how many ATP from the TCA cycle and ox phos

20

Aerobic Oxidation of Glucose Yields how many ATP in eukaryotes

30

Aerobic Oxidation of Glucose Yields how many ATP in prokaryotes

32

control

The key what points in the citric acid cycle are the reactions catalyzed by isocitrate dehydrogenase and α-ketoglutarate dehydrogenase

fluxes are affected by the concentrations of substrates and products:
end products ATP and NADH are what

inhibitory

fluxes are affected by the concentrations of substrates and products:
ADP and NAD+ are what

stimulatory

glucose

pyruvate dehydrogenase, which controls entry of what- derived acetyl CoA into the cycle, is
also regulated

PFK is what regulated by citrate, which reports on the status of the citric acid cycle and need for carbon building blocks for biosynthesis

negatively

The Citric Acid Cycle also has a Major Role in Several what Pathways (synthesis)

Anabolic

Anaplerotic

What Reactions Replenish Citric Acid Cycle Intermediates

chemical

anaplerotic reactions = what reactions that replenish intermediates
(from Gr. ‘to fill up’)

pyruvate what synthesizes oxaloacetate by the carboxylation of pyruvate. Important anaplerotic reaction in liver, kidney, and brown adipose tissue. The reaction uses ATP, but allows the cycle to continue

carboxylase