Biochemistry: Coenzyme A and Pyruvate Metabolism

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Questions and Answers

What enzymatic reaction occurs to convert citrate into isocitrate?

Isomerization via cis-aconitate (correct)

Hydration

Oxidation

Decarboxylation

What is produced during the oxidative decarboxylation steps of the TCA cycle?

ATP

FADH2 (correct)

GTP

CO2 (correct)

Which enzyme catalyzes the conversion of malate to oxaloacetate?

Succin dehydrogenase

Citrate synthase

Aconitase

Malate dehydrogenase (correct)

What type of group acts as a coenzyme for aconitase during the isomerization process?

Iron-sulfur (Fe-S) center Signup and view all the answers

Which product is generated by substrate-level phosphorylation in the TCA cycle?

GTP Signup and view all the answers

What is the consequence of fluoroacetate poisoning on the TCA cycle?

Inhibition of aconitase Signup and view all the answers

What is a characteristic feature of the TCA cycle in relation to metabolism?

It intersects multiple other metabolic pathways Signup and view all the answers

Which of the following substrates enters the TCA cycle after being converted to Acetyl-CoA?

Pyruvate Signup and view all the answers

What is the primary function of Coenzyme A in cellular metabolism?

To accept and carry acetyl groups Signup and view all the answers

Which statement about coenzymes is true?

They fulfill their function and then dissociate from enzymes Signup and view all the answers

Which of the following is not a prosthetic group in the Pyruvate Dehydrogenase Complex?

Coenzyme A (CoA) Signup and view all the answers

What is the main consequence of thiamine deficiency in relation to pyruvate metabolism?

Inability to oxidize pyruvate appropriately Signup and view all the answers

What does the oxidative decarboxylation of pyruvate primarily produce?

Acetyl-CoA and CO2 Signup and view all the answers

How many turns of the TCA cycle occur per glucose molecule?

2 Signup and view all the answers

What is a characteristic feature of the Pyruvate Dehydrogenase Complex?

It prevents substrate theft through substrate channelling Signup and view all the answers

Which vitamin is NOT correctly associated with its function in metabolism?

Thiamine (B1) - part of CoA structure Signup and view all the answers

Study Notes

Coenzyme A and Coenzymes

Coenzyme A (CoA) is essential for accepting and transporting acetyl groups.
Coenzymes are transient molecules, participating in enzyme functions without being permanently part of the enzyme’s structure.

Conversion of Pyruvate to Acetyl-CoA

Pyruvate conversion is catalyzed by the Pyruvate Dehydrogenase Complex (PDC).
PDC requires five coenzymes for its function, including three prosthetic groups: Thiamine pyrophosphate (TPP), lipoyllysine, and FAD, all covalently bound.
NAD+ and CoA-SH function as co-substrates during this process.

Pyruvate Dehydrogenase Complex (PDC)

PDC can reach sizes up to 10 MDa and is found in the mitochondrial matrix of eukaryotic cells.
It consists of three functional proteins and coordinates three sequential enzymatic reactions:
- Enzyme 1: Converts pyruvate to a hydroxyethyl intermediate, followed by oxidation.
- Enzyme 2: Forms acetyl-CoA.
- Enzyme 3: Reduces FAD and oxidizes lipoyllysine, converting FADH2 to reduce NAD.

Advantages of Substrate Channelling in PDC

Substrate channelling maintains high local concentrations of substrates and prevents intermediates from diffusing away.
This mechanism enhances the efficiency of acetyl group use.

B Vitamins and Their Role

TPP is a derivative of Vitamin B1, while NAD+ corresponds to Vitamin B3 (niacin).
Coenzyme A contains pantothenic acid (Vitamin B5).
Riboflavin (B2) plays a role in the electron transport chain, and biotin (B7) is important for gluconeogenesis.
Thiamine deficiencies can disrupt normal pyruvate oxidation, particularly affecting brain function, leading to conditions like Beri-beri.

The TCA Cycle

Also known as the Tricarboxylic acid cycle, Krebs cycle, or citric acid cycle, it metabolizes acetyl-CoA.
The cycle produces byproducts including 2 CO2, 3 NADH, 1 FADH2, and 1 GTP, with each glucose molecule leading to two cycles.

TCA Cycle Steps

Steps involve citrate formation, isomerization, oxidative decarboxylation yielding NADH, substrate-level phosphorylation for GTP, and further oxidations to regenerate NADH.
Aconitase catalyzes the isomerization of citrate to isocitrate using an iron-sulfur coenzyme.

Key Points in TCA Cycle

α-Ketoglutarate Dehydrogenase has similar characteristics to PDC, employing identical coenzymes and mechanisms.
TCA intermediates serve as critical biosynthetic precursors, integrating various metabolic pathways.

Malate Shuttle

NADH generated in glycolysis cannot directly enter mitochondria; instead, it relies on the malate-aspartate shuttle.
Cytoplasmic malate dehydrogenase converts oxaloacetate to malate, which then enters mitochondria for regeneration of NADH.

Case Study: Fluoroacetate (1080)

Used to control feral dingo populations; poisoning leads to symptoms like excessive howling, seizures, and eventual death.
Fluoroacetate disrupts the TCA cycle by binding aconitase, resulting in elevated citrate levels causing hypocalcemia and decreased ATP production.

Summary

Cellular respiration consists of three stages, with the TCA cycle being the second stage.
Acetyl-CoA enters the TCA cycle with the net reaction producing reduced cofactors and CO2.
There are two oxidative decarboxylation steps within the cycle, crucial for cellular metabolism.

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Description

Explore the crucial role of Coenzyme A in acetyl group transport and the function of the Pyruvate Dehydrogenase Complex in converting pyruvate to acetyl-CoA. This quiz covers the essential coenzymes and enzymatic reactions involved in this metabolic pathway. Test your understanding of these fundamental biochemistry concepts!