29.6 Conversion of Pyruvate to Acetyl CoA
3 min read•may 7, 2024
() is the key to turning into . This process bridges and the , kicking off in earnest.
The PDC is a team of enzymes that work together to break down pyruvate. It uses special helpers like to make the chemical reactions happen smoothly, ensuring our cells get the energy they need.
Pyruvate Dehydrogenase Complex
Process of oxidative decarboxylation
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- Pyruvate converted to acetyl by complex (PDC) in
- Involves removes carbon dioxide molecule and oxidizes remaining compound
- Pyruvate loses one carbon atom as , remaining two-carbon unit oxidized to form acetyl CoA
- Overall reaction:
- PDC multienzyme complex consists of three main components:
- Pyruvate dehydrogenase () catalyzes of pyruvate
- () transfers acetyl group to CoA
- () regenerates oxidized lipoamide
- Conversion process involves several steps and cofactors including thiamin diphosphate (), , coenzyme A (CoA), and
- This process links glycolysis to the
Role of thiamin diphosphate
- Thiamin diphosphate (TPP) cofactor derived from ###Vitamin_B1_()_0### essential for first step of pyruvate conversion
- TPP bound to active site of pyruvate dehydrogenase (E1 component of PDC)
- Key roles of TPP in first step:
- Acts as electron sink stabilizing negative charge on two-carbon unit after decarboxylation
- Facilitates cleavage of C-C bond between carboxyl group and α-carbon of pyruvate
- Reaction mechanism involving TPP:
- Reactive carbon of TPP forms covalent bond with carbonyl carbon of pyruvate
- Bond formation promotes decarboxylation releasing CO2 and leaving two-carbon intermediate
- Hydroxyethyl-TPP intermediate ready for next step in PDC reaction sequence
Key reactions in pyruvate dehydrogenase complex
- Decarboxylation (Pyruvate dehydrogenase, E1):
- TPP bound to E1 attacks carbonyl carbon of pyruvate forming covalent adduct
- Decarboxylation occurs releasing CO2 and generating hydroxyethyl-TPP intermediate
- (Dihydrolipoyl transacetylase, E2):
- Hydroxyethyl group transferred from TPP to lipoyl group of E2 forming intermediate
- Coenzyme A (CoA) attacks acetyl group forming acetyl CoA and reduced lipoamide
- Regeneration of oxidized lipoamide (Dihydrolipoyl dehydrogenase, E3):
- Reduced lipoamide oxidized by E3 using FAD as electron acceptor
- FAD regenerated by transferring electrons to forming NADH
- Overall process tightly regulated and coordinated with products of one reaction serving as substrates for next
- PDC example of where intermediates directly transferred between active sites without diffusing into surrounding medium
Cellular Respiration Overview
- Pyruvate conversion to acetyl CoA is a crucial step in cellular respiration
- Cellular respiration consists of several interconnected processes:
- Glycolysis: Glucose breakdown to pyruvate in cytoplasm
- Pyruvate conversion to acetyl CoA (covered in this guide)
- Citric acid cycle: Acetyl CoA oxidation in mitochondrial matrix
- : Electron transfer through protein complexes in inner mitochondrial membrane
- : ATP synthesis driven by proton gradient generated by electron transport chain
Key Terms to Review (34)
Acetyl CoA: Acetyl Coenzyme A (acetyl CoA) is a crucial metabolic intermediate that serves as the central hub for several important biochemical pathways, including the citric acid cycle, fatty acid synthesis, and the conversion of pyruvate to acetyl CoA. It is the primary entry point for the oxidation of carbohydrates, fats, and some amino acids to generate energy in the form of ATP.
Acetyl-Lipoamide: Acetyl-lipoamide is a cofactor involved in the conversion of pyruvate to acetyl-CoA, a crucial step in the metabolic pathway known as the citric acid cycle or Krebs cycle. It serves as a carrier molecule, transferring the acetyl group from pyruvate dehydrogenase to coenzyme A, thereby facilitating the entry of acetyl units into the Krebs cycle for energy production.
Acyl Transfer: Acyl transfer is a fundamental chemical reaction in which an acyl group (a carbonyl group attached to an alkyl or aryl group) is transferred from one molecule to another. This process is crucial in various biological and organic chemistry contexts, including the metabolism of carboxylic acid derivatives and the conversion of pyruvate to acetyl CoA.
Carboxylic acid, RCO2H: Carboxylic acids are organic compounds characterized by the presence of at least one carboxyl group (-COOH), where "R" represents the rest of the molecule that can be varying carbon-containing structures. These acids are widely recognized for their sour taste and strong odors, playing pivotal roles in biochemical processes and industrial applications.
Cellular Respiration: Cellular respiration is the metabolic process by which cells convert the chemical energy from nutrients into a form of energy that can be used by the cell, typically in the form of adenosine triphosphate (ATP). It is a crucial process that occurs in the mitochondria of eukaryotic cells and is essential for sustaining life.
Citric acid cycle: The Citric Acid Cycle is a series of chemical reactions used by all aerobic organisms to generate energy through the oxidation of acetate derived from carbohydrates, fats, and proteins into carbon dioxide. Additionally, it provides precursors for certain amino acids as well as the reducing agent NADH that is used in numerous other biochemical reactions.
Citric Acid Cycle: The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a series of chemical reactions that occur in the mitochondria of cells. It is a key metabolic pathway that generates energy in the form of ATP through the oxidation of acetyl-CoA derived from the breakdown of carbohydrates, fats, and proteins.
CO2: Carbon dioxide (CO2) is a colorless, odorless gas that is a byproduct of cellular respiration and combustion processes. It is a crucial molecule in the context of polar covalent bonds and dipole moments, as well as the conversion of pyruvate to acetyl CoA during cellular metabolism.
CoA: Coenzyme A (CoA) is a crucial cofactor involved in numerous metabolic pathways, particularly in the conversion of pyruvate to acetyl CoA, a key step in cellular energy production through the citric acid cycle.
Decarboxylation: Decarboxylation is a chemical reaction that involves the removal of a carboxyl group (–COOH) from a molecule, typically resulting in the release of carbon dioxide (CO2). This process is important in various organic chemistry reactions and metabolic pathways.
Dihydrolipoyl Dehydrogenase: Dihydrolipoyl dehydrogenase is an enzyme that plays a crucial role in the conversion of pyruvate to acetyl-CoA, a key step in the metabolic pathway known as the pyruvate dehydrogenase complex. This enzyme is responsible for the oxidation of the dihydrolipoyl group, regenerating the oxidized lipoyl group for further rounds of the pyruvate dehydrogenase reaction.
Dihydrolipoyl Transacetylase: Dihydrolipoyl transacetylase is a key enzyme involved in the conversion of pyruvate to acetyl CoA, a crucial step in cellular energy production through the citric acid cycle. This enzyme facilitates the transfer of the acetyl group from pyruvate dehydrogenase to coenzyme A, forming acetyl CoA which can then enter the citric acid cycle.
E1: E1 is a type of organic reaction mechanism in which the first step involves the unimolecular elimination of a good leaving group from a substrate, resulting in the formation of a carbocation intermediate. This is then followed by the removal of a proton from an adjacent carbon, leading to the formation of a new carbon-carbon double bond.
E2: E2 (Elimination, bimolecular) is a type of organic reaction mechanism where a base removes two atoms, typically a hydrogen and a leaving group, from adjacent carbon atoms in a single step, resulting in the formation of a new carbon-carbon double bond.
E3: E3 is an enzyme complex that catalyzes the final and rate-limiting step in the conversion of pyruvate to acetyl-CoA, a crucial process in cellular respiration and energy production.
Electron Transport Chain: The electron transport chain is a series of protein complexes and electron carriers located in the inner membrane of mitochondria that are responsible for the final stages of cellular respiration. It is a crucial component of the process that converts the energy stored in organic molecules into the universal energy currency, ATP.
FAD: FAD, or Flavin Adenine Dinucleotide, is a coenzyme that plays a crucial role in various metabolic processes within the body. It serves as an essential cofactor for numerous enzymes involved in energy production, oxidation-reduction reactions, and other vital biochemical pathways.
Glycolysis: Glycolysis is the metabolic pathway that converts glucose, a six-carbon sugar, into two molecules of pyruvate, a three-carbon compound. This process is the first step in the catabolism of carbohydrates and is a fundamental part of cellular respiration, providing energy in the form of ATP to the cell.
Hydroxyethyl-TPP: Hydroxyethyl-TPP is an important intermediate in the conversion of pyruvate to acetyl-CoA, a key step in cellular respiration. It is formed when the pyruvate dehydrogenase complex catalyzes the oxidative decarboxylation of pyruvate, releasing carbon dioxide and producing a hydroxyethyl group attached to the cofactor thiamine pyrophosphate (TPP).
Lipoic Acid: Lipoic acid, also known as alpha-lipoic acid, is an essential cofactor that plays a crucial role in the conversion of pyruvate to acetyl-CoA and in the citric acid cycle. It is a sulfur-containing compound that facilitates the transfer of acyl groups and the decarboxylation of alpha-keto acids, making it indispensable for cellular energy production.
Mitochondrial Matrix: The mitochondrial matrix is the dense, liquid-filled space within the inner membrane of a mitochondrion, the powerhouse of the cell. It is the site where key metabolic processes like the citric acid cycle and fatty acid oxidation take place, providing the cell with the energy it needs to function.
NAD+: NAD+ (Nicotinamide Adenine Dinucleotide) is an essential coenzyme involved in numerous metabolic processes within the body. It plays a crucial role in the oxidation of organic compounds, serving as an electron acceptor in various redox reactions.
NADH: NADH, or nicotinamide adenine dinucleotide, is a coenzyme that plays a crucial role in numerous metabolic processes within the body. It is the reduced form of NAD+, an important electron carrier that is involved in oxidation-reduction reactions throughout the cell's energy-producing pathways.
Oxidative Decarboxylation: Oxidative decarboxylation is a crucial metabolic process that converts pyruvate, the end product of glycolysis, into acetyl-CoA, a key entry point for the citric acid cycle. This reaction, catalyzed by the pyruvate dehydrogenase complex, simultaneously removes a carboxyl group (CO2) from pyruvate and oxidizes the remaining two-carbon fragment to form acetyl-CoA, which can then enter the citric acid cycle for further energy production.
Oxidative Phosphorylation: Oxidative phosphorylation is the metabolic pathway in which cells use enzymes and electron transport chains to convert the energy released by the oxidation of nutrients into adenosine triphosphate (ATP), the primary energy currency of the cell. It is a crucial process that occurs in the mitochondria and is the final stage of cellular respiration.
PDC: PDC, or the Pyruvate Dehydrogenase Complex, is a crucial enzyme complex responsible for the conversion of pyruvate, the end product of glycolysis, into acetyl-CoA, which can then enter the Citric Acid Cycle for further energy production through cellular respiration.
Pyruvate: Pyruvate is a key intermediate molecule in cellular metabolism, serving as a central hub that connects various metabolic pathways. It is the final product of glycolysis, the process of breaking down glucose to generate ATP, and plays a crucial role in energy production, biosynthesis, and other essential metabolic processes within the body.
Pyruvate Dehydrogenase: Pyruvate dehydrogenase is a critical enzyme complex that catalyzes the irreversible conversion of pyruvate, the end product of glycolysis, into acetyl-CoA, which then enters the citric acid cycle for further energy production.
Pyruvate Dehydrogenase Complex: The pyruvate dehydrogenase complex is a large, multienzyme complex that catalyzes the conversion of pyruvate, the end product of glycolysis, into acetyl-CoA, which can then enter the citric acid cycle for further energy production.
Substrate Channeling: Substrate channeling is a metabolic process where the product of one enzymatic reaction is directly transferred to the active site of the next enzyme in a metabolic pathway, without being released into the bulk solution. This allows for efficient and coordinated metabolic flux by minimizing the diffusion and loss of intermediate metabolites.
Thiamin Diphosphate: Thiamin diphosphate, also known as thiamine pyrophosphate (TPP), is an essential cofactor involved in several crucial metabolic pathways, including the conversion of pyruvate to acetyl-CoA. It serves as a cofactor for enzymes that catalyze decarboxylation and other key reactions in cellular respiration and energy production.
Thiamine: Thiamine, also known as vitamin B1, is an essential nutrient that plays a crucial role in the conversion of pyruvate to acetyl CoA, a key step in the metabolism of carbohydrates. As a cofactor for several enzymes involved in this process, thiamine is essential for energy production and overall cellular function.
TPP: TPP, or Thiamine Pyrophosphate, is a coenzyme derived from the vitamin thiamine (vitamin B1) that plays a crucial role in the conversion of pyruvate to acetyl-CoA, a key step in the metabolic process known as the Conversion of Pyruvate to Acetyl CoA.
Vitamin B1 (Thiamine): Vitamin B1, also known as thiamine, is an essential nutrient that plays a crucial role in the conversion of pyruvate to acetyl CoA, a key step in the metabolism of carbohydrates. As a cofactor for several enzymes involved in this process, vitamin B1 is vital for energy production and overall metabolic function.