TCA cycle is a central pathway for___ ____ from several metabolic pathways when acetyl CoA can be generated

-recovering energy

Acetyl CoA is oxidized in the TCA cycle, where intermediates are

utilized in a circular pathway

Glycolysis occurs in the cytoplam and doesnt require energy. Meanwhile, the TCA cycle occurs in the

mitochondria

The TCA cycle allows for the oxidation of pyruvate to CO₂ under_____conditions, and yields about ______ATP

-aerobic

-36

Do the electrons from glucose oxidation feed into the electron transport pathway, driving synthesis of ATP?

YES

What is Acetyl CoA oxidized to?

CO₂

Electrons stored as NADH and FADH2 are delivered to a________ to the
final electron acceptor O2.

-membrane-associated electron-transport chain

Electron transfer is coupled
to a proton gradient across the membrane to drive the
synthesis of ATP in a process known as____

-oxidative phosphorylation.

How many electrons are removed when a complete oxidation of glucose to CO₂ occurs?

-24 electrons

How many total electrons are in PDHC?

-4 electrons total in 2 pyr-> acetyl-CoA

How many total electrons are in TCA cycle?

-8 electrons for each acetyl CoA (16 total)

These electrons are stored as ___ and ___ used to fuel oxidative phosphorylation.

-NADH

-FADH₂

Flavin coenzymes can exist in three oxidation states

FAD, FMN, and riboflavin

The three oxidation states allows for flavin coenzymes to participate in

one-electron or two-electron transfer reactions.

Catalyze many reactions in biological systems and work with many electron donors and acceptors

Flavoproteins

FADH₂ can transfer either __ or __ e^- at a time

-1

-2

FADH, FAD, FADH₂ are made form the vitamin

riboflavin

What structure is this?

FADH₂

What structure is this?

FAD

What is the source of acetyl CoA?

pyruvate

The reaction that converts pyruvate to acetyl CoA is catalyzed by the

-pyruvate dehydrogenase complex (PDC or PDHC)

permeable to anything smaller than 5 kD

Outer membrane

permeable only to O₂, H₂O, and CO₂

Inner membrane

How does pyruvate make its way into the mitochondrial matrix?

-it travels through a channel in the outer membrane and an H⁺/pyruvate symporter in the inner membrane

From pyruvate to Acetyl CoA:

oxidation by NAD⁺ and formation of a thioester

What is the function of CoA?

-a carrier of acetyl and other acyl groups

What is the reaction of a pyruvate DH complex?

What three enzymes is pyruvate dehydrogenase made of?

_pyruvate dehydrogenase(E1)

-Dihydrolipoyl transacetylase (E2)

-Dihydrolipoyl dehydrogenase (E3)

What are the 5 cofactors of pyruvate dehydrogenase?

-TPP

-NAD

-FAD

-Lipoic Acid

-CoA

Pyruvate conversion to Acetly CoA

What is the purpose of TPP cofactor?

facilitates decarboxylation

What is the purpose of lipoic acid?

-bound to a lysyl residue to form lipoamide that is reduced to from dihydrolipoamide

-serves as a swinging arm to transfer intermediates from E1, E2, E3

Arsenic poisoning is a toxic compound that binds to

sulfhydryl compounds

The inactivation of lipoamide-containing compounds such as pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase__-

halts respiration

Arsenic compounds are more toxic to______ and was used to treat ___,___,___

-microorganisms

-syphilis, bacteria, and parasitic diseases

TPP( vitamin B1/thiamine) deficiency results in

pain, paralysis, wasting, and heart failure

TPP being used in pyruvate DH

In pyruvate decarboxylase, hydrooxyethyl-TPP is

cleaved to release acetaldehyde +TPP

In pyruvate DH reaction, hydroxyethyl-TPP transfers H₃C-(C=O)- to_____ and ____occurs producing dihydrolipoate

-lipoic acid

-oxidation

T or F: Humans can make lipoic acid (it is a vitamin)

false

The nucleophilic attack by CoA at carbonyl carbon results in transfer of acetyl group to CoA generating

acetyl CoA

When the acetyl group is transferred to CoA, FAD and NAD⁺ are used to

reclose (oxidize) S-S of lipoic acid

E2 is a proper

oxidation state

PDHC mechanism

KNOW THIS TABLE

Thiamine is a vitamin in B1 and can be found in

nuts, meats, and whole grains

Lipoic acid is made from fatty acid precursors in animals and can be found in

spinach, broccoli, yeast, rice bran, red organic meat

CoA biosynthesis requires cysteine pantothenate and ATP and is

lesser known than vit. B5 because all foods are a source of B5

FAD/FMN is synthesized from_____ and can be found in_____-

-riboflavin

-eggs, organ meats, low-fat milk, cereals, bread, and grain products

NAD⁺ biosynthesized from____, but relies on salvage pathways that use______

-tryptophan

-niacin

A long lasting drop or rise of ΔΨmvs normal levels may

induce unwanted loss of cell viability and be a cause of various pathologies

ΔΨmvs drives inward transport of____ and outward transport of _____

-cations

-anions

ΔΨmvs is an important factor in selection of

non-functional mitochondria

1. Entry of new carbon units into the TCA cycle is from pyruvate or oxidation of fatty acids

2. Transfer of the 2-C acetyl CoA to 4C OAA yields citrate

3. A dehydration-rearrangement yields isocitrate

4. two successive decarboxylation produce alpha-KG and then succinyl CoA

5. Multiple rearrangements to regenerate OAA

The chemical logic of the TCA cycle

reaction where 2C unit of acetyl CoA is introduced into the TCA cycle by addition to the 4C unit OAA to from citrate

1. Citrate synthase

The Cα of the acetyl group in acetyl-CoA is acidic and can be deprotonated to form a

carbanion

The carbanion is a strong ______that can attack the α-carbonyl of ______

-nucleophile

-oxaloacetate

Due to citrates poor oxidation, the enzyme___ catalyzes an isomerization reaction

2. aconitase

Aconitase uses an_____ to achieve stereospecificity

iron-sulfur cluster

Is a hydride removal followed by a decarboxylation and is a link to the electron transport pathway because it makes NADH

3. Isocitrate dehydrogenase

Isocitrate dehydrogenase produces the 1st NADH and the CO₂ released came from the

end of OXAL

α-ketoglutarate dehydrogenase catalyzes the_________of the TCA cycle

2nd oxidative decarboxylation

Enzyme is nearly identical to pyruvate dehydrogenase and the 2nd NADH is produced

4. α-ketoglutarate dehydrogenase

Uses 5 coenzymes: TPP, CoASH, lipoic acid, NAD⁺, and FAD

α-ketoglutarate dehydrogenase

α-Ketoglutarate dehydrogenase is a very __, _____ reaction

-exergonic

-irreversible

The 60 subunits are made up of:

-pyruvate dehydrogenase: 24(E1)

-dihydrolipoyl transacetylase: 24(E2)

-dihydrolipoyl dehydrogenase:12(E3)

Harvest "high energy" thioester bond to make GTP. Since succinate is symmetric, we can no longer distinguish which carbons came from acetyl coA

5. Succinyl-CoA synthetase

It is considered to be the substrate-level phosphorylation

Succinyl-CoA synthetase reaction

During Succinyl-CoA synthetase the mechanism involves formation of a ________to produce_____

-phosphohistidine

-succinate

A____is made after succinyl-CoA synthetase

nucleoside triphosphate

It is near equilibrium. DH->FADH₂ rather than NADH

6. Succinate dehydrogenase

(Δℰ^o‘= ℰ^o‘ (acceptor) - ℰ^o‘(donor))

Remember this!!

Reduction potential

Practice this math question

Succinate dehydrogenase contains three types of Fe-S centers:

a 4Fe-4S center, a 3Fe-4S, and a 2Fe-2S center

Succinate DH involves hydride removal by ____. This enzyme is part of the electron transport pathways in the inner _____

-FAD

-mitochondrial membrane

The electrons transferred from succinate to FAD(to form FADH₂) are passed to____in electron transport pathway

ubiquinone

Fumarase converts fumarate->malate by

adding water

Fumarase causes the

hydration across the double bond

Malate DH _____malate-> OAA

reversibly oxidizes

The carbon that gets oxidized received an OH group in the previous reaction. Is NAD⁺-dependent oxidation

8. Malate oxidation

The carbon atoms of Acetyl-CoA have diff. fates

Electrons stored as NADH and FADH₂ are delivered to a membrane associated ETC to the final electron acceptor O₂. Electron transfer is coupled to a proton gradient across the membrane to drive the synthesis of ATP in a process known as

oxidative phosphorylation