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What is the general path that glucose takes to become Acetyl-CoA?

Glucose undergoes glycolysis, yielding pyruvate.

Pyruvate is oxidized by pyruvate dehydrogenase complex, yielding Acetyl-CoA.

What are the 3 stages of cellular respiration?

1. Production of Acetyl-CoA
2. Oxidation of Acetyl-CoA, yielding NADH and FADH2 and GTP
3. Oxidative phosphorylation: synthesis of ATP and reduction of oxygen to water.

Why is pyruvate a logical point of metabolic regulation?

It links two huge metabolic pathways: glycolysis and the citric acid cycle.

What are the different names for the citric acid cycle?

TCA: tricarboxylic acid cycle

Krebs cycle

What drives the production of ATP in the oxidative phosphorylation phase?

Electron flow.

What are the functional groups part of Coenzyme A? How does it bond with acetate?

B-mercaptoethylamine,

pantothenic acid,

adenine, and

ribose 3’-phosphate.

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It bonds to acetate via a thioester bond.

What cofactors are required for conversion of pyruvate to acetyl-CoA?

TPP, lipoate, FAD, NAD+, and CoA-SH.

What are the two end products of conversion of pyruvate?

Acetyl CoA + CO2

How does pyruvate from glycolysis enter the mitochondria?

MPC: mitochondrial pyruvate carrier.

Not passively diffused, MPC is a **pyruvate-specific symporter** coupled with H+.

What is E1 in the pyruvate dehydrogenase complex?

E1: pyruvate dehydrogenase

What is E2 in the pyruvate dehydrogenase complex?

E2: dihydrolipoyl (lipoate) transacetylase

What is E3 in the pyruvate dehydrogenase complex?

E3: dihydrolipoyl (lipoate) dehydrogenase

What is the overall reaction catalyzed by PDH complex?

oxidative decarboxylation

What is lipoate? Describe its structure and function. How is it bound to PDH?

One of the coenzymes required for conversion of pyruvate.

It was two thiol groups that undergo reversible oxidation to a disulfide bond.

It serves as an electron (hydrogen) and acyl carrier.

**It is covalently bound to E2 via lysine residue**.

What is the function of TPP?

Breaks an alpha carbonyl bond (which is unfavorable), carrying out the removal of a CO2 group from a molecule.

Describe the five steps that pyruvate undergoes to form Acetyl-CoA via the PDH.

1. Pyruvate is decarboxylated, yielding aldehyde (acetal).
2. Acetyl group is transferred to lipolylysine, yielding acetyl lipoyllysine.
3. CoA-SH binds to acetyl lipoyllysine, forming **acetyl CoA.**
4. *FAD oxidizes (meaning FAD is reduced itself) lipoyllysine to allow it to bind further acetyls again.*
5. *NAD+ is reduced to regenerate FAD.*

Steps 4 and 5 are regenerative steps to allow cyclic proliferation.

The PDH uses a method called substrate ________ to improve catalytic efficiency.

channeling

What is the importance of E2 with regard to “substrate channeling” ? (What is substrate channeling?)

Substrate channeling is the movement of intermediates directly from one enzyme to another without release. This occurs via E2 (lipoate)’s long side chain, which delivers intermediates to each enzyme.

What are the inputs and outputs of the citric acid cycle?

Input:

**1 acetyl-CoA**

Output:

**2 CO2**

**3 NADH**

**1 FADH2**

**1 GTP**

What are two functions of the citric acid cycle?

1. Energy production
2. Metabolite production required for anabolism of biomolecules (nucleic acids, proteins, sugars, and fats).

What are the net outputs of the citric acid cycle?

3 NADH

1 FADH

1 GTP

List the names of each intermediate of the citric acid cycle, in order, starting with oxaloacetate.

Oxaloacetate

Citrate

Cis-aconitate

Isocitrate

a-Ketoglutarate

Succinyl-CoA

Succinate

Fumarate

Malate

Oxaloacetate.

How many reactions within the citric acid cycle are reversible, and which ones?

3; two form CO2, and one is the formation of citrate.