21.8 Chemistry of Thioesters and Acyl Phosphates: Biological Carboxylic Acid Derivatives
3 min read•may 7, 2024
and are key players in cellular metabolism. These molecules, like , have a unique structure that makes them more reactive than other carboxylic acid derivatives. This reactivity is crucial for their roles in important biological processes.
Nucleophilic acyl substitution reactions involving thioesters are vital in biology. For example, , a component of cell surface glycoproteins and , is formed when glucosamine reacts with acetyl-CoA. This showcases how thioesters participate in building essential biological molecules.
Thioesters and Acyl Phosphates
Structure and function of thioesters
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- Contain a sulfur atom instead of the oxygen atom in the ester functional group
- General structure: R-C(=O)-S-R', where R and R' are alkyl or aryl groups
- Acetyl (Acetyl-CoA) is a crucial molecule in cellular metabolism
- Consists of an acetyl group (CH3-C(=O)-) bound to Coenzyme A (CoA) through a bond
- Plays a central role in the , , and other
- Thioesters are more reactive than oxygen esters due to the weaker C-S bond compared to the C-O bond
- The weaker C-S bond makes the carbonyl carbon more electrophilic and susceptible to
- Allows thioesters to participate readily in various biological reactions (, fatty acid synthesis)
Reactivity of acyl CoA vs carboxylic acids
- Acyl CoA compounds (thioesters) are more reactive than carboxylic acids and other carboxylic acid derivatives
- Reactivity order of carboxylic acid derivatives (most reactive to least reactive):
- Acyl chlorides (R-C(=O)-Cl)
- Anhydrides (R-C(=O)-O-C(=O)-R)
- Thioesters (R-C(=O)-S-R')
- Esters (R-C(=O)-O-R')
- Amides (R-C(=O)-NH2)
- Carboxylic acids (R-C(=O)-OH)
- The high reactivity of acyl CoA compounds enables them to participate readily in biological reactions
- Citric acid cycle
- Fatty acid synthesis
- Carboxylic acids are less reactive due to the stronger C-O bond and the stabilizing effect of the hydroxyl group
Nucleophilic acyl substitution in biology
- Involves the replacement of the leaving group in a carboxylic acid derivative by a nucleophile
- The nucleophile attacks the electrophilic carbonyl carbon, displacing the leaving group and forming a new bond
- N-Acetylglucosamine () is formed by the nucleophilic acyl substitution reaction between glucosamine (a nucleophilic amine) and acetyl-CoA (a thioester)
- The amine group of glucosamine attacks the electrophilic carbonyl carbon of acetyl-CoA
- Coenzyme A (the leaving group) is displaced
- An amide bond is formed
- The resulting product is N-acetylglucosamine, with the acetyl group (CH3-C(=O)-) attached to the amine group of glucosamine
- GlcNAc is an important component of cell surface glycoproteins and chitin
- Chitin is a structural polysaccharide found in the exoskeletons of arthropods (insects, crustaceans) and cell walls of fungi
- Other examples of biologically important molecules formed by nucleophilic acyl substitution reactions:
- (a neurotransmitter)
- Acetylated proteins (involved in gene regulation and cellular signaling)
- Fatty acid synthesis builds long-chain fatty acids from acetyl-CoA units
Biological Reactions and Catalysis
- : The process of adding an acyl group to a molecule, often catalyzed by enzymes in metabolic pathways
- : The breakdown of molecules through reaction with water, common in the metabolism of thioesters and
- : Proteins that accelerate chemical reactions in biological systems, often involved in the formation and breakdown of thioesters and acyl phosphates
- Metabolic pathways: Series of chemical reactions in cells that maintain life, frequently involving thioesters and acyl phosphates as intermediates or energy carriers
Key Terms to Review (28)
1,3-bisphosphoglycerate: 1,3-bisphosphoglycerate is a key intermediate in the glycolysis pathway, the process of breaking down glucose to produce energy. It is also an important acyl phosphate compound that plays a role in the chemistry of thioesters and carboxylic acid derivatives in biological systems.
Acetyl-CoA: Acetyl-CoA is a crucial metabolic intermediate that serves as a central hub in various cellular processes, including the citric acid cycle, fatty acid synthesis, and acetylation reactions. It is the primary entry point for the oxidation of carbohydrates, fats, and some amino acids, linking these catabolic pathways to the production of energy in the form of ATP.
Acetyl-CoA Synthetase: Acetyl-CoA synthetase is an enzyme that catalyzes the conversion of acetate, coenzyme A, and ATP into acetyl-CoA, AMP, and pyrophosphate. This enzyme plays a crucial role in the metabolism of carboxylic acid derivatives, particularly in the context of thioesters and acyl phosphates, which are important biological molecules.
Acetylcholine: Acetylcholine is a neurotransmitter that plays a crucial role in the functioning of the nervous system, particularly in the transmission of signals between neurons and target cells. It is involved in various physiological processes, including muscle contraction, cognitive function, and autonomic nervous system regulation.
Acyl Phosphate: An acyl phosphate is a high-energy compound formed by the covalent attachment of a carboxylic acid group (acyl group) to a phosphate group. These compounds are important intermediates in various biological processes, particularly in the context of energy-releasing reactions and the synthesis of biological macromolecules.
Acyl phosphates: Acyl phosphates are high-energy carboxylic acid derivatives where the acyl group is bonded to a phosphate group. They are key intermediates in nucleophilic acyl substitution reactions, facilitating the transfer of the acyl group due to their high reactivity.
Acyl Phosphates: Acyl phosphates are a class of carboxylic acid derivatives that feature a phosphate group attached to the carbonyl carbon. These compounds are important intermediates in biological processes, particularly in the context of energy transfer and storage within living organisms.
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.
Acylation: Acylation is a chemical reaction in which an acyl group (such as an acetyl or benzoyl group) is introduced into a molecule, typically by the reaction of a carboxylic acid or its derivative with another compound. This process is central to the preparation of carboxylic acids, nucleophilic acyl substitution reactions, the chemistry of thioesters and acyl phosphates, and the reactions of amines.
Chitin: Chitin is a natural polysaccharide composed of N-acetylglucosamine units. It is a structural component found in the exoskeletons of arthropods, such as crustaceans and insects, as well as in the cell walls of certain fungi. Chitin's unique properties and abundance in nature make it a versatile and important biomaterial with applications in various fields, including 21.8 Chemistry of Thioesters and Acyl Phosphates: Biological Carboxylic Acid Derivatives and 25.10 Some Other Important Carbohydrates.
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.
Coenzyme A: Coenzyme A (CoA) is a critical cofactor involved in numerous metabolic pathways, including the breakdown and synthesis of carbohydrates, fats, and amino acids. It plays a central role in connecting various biological reactions and serves as an essential component in the Citric Acid Cycle, the biosynthesis of fatty acids, and the activation of carboxylic acids.
Enzyme Catalysis: Enzyme catalysis is the process by which enzymes, which are biological catalysts, accelerate the rate of chemical reactions in living organisms. Enzymes achieve this by lowering the activation energy required for a reaction to occur, allowing it to proceed more rapidly under physiological conditions.
Fatty Acid Synthesis: Fatty acid synthesis is the metabolic pathway that converts acetyl-CoA into long-chain fatty acids, which are essential components of cell membranes, energy storage, and various biological processes. This term is particularly relevant in the context of understanding the chemistry of thioesters and acyl phosphates, as well as some biological carbonyl condensation reactions.
GlcNAc: GlcNAc, or N-acetylglucosamine, is an important monosaccharide that plays a crucial role in the chemistry of thioesters and acyl phosphates, which are key biological carboxylic acid derivatives. It serves as a building block for various biomolecules and is involved in numerous cellular processes.
Hydrolysis: Hydrolysis is a chemical reaction in which a compound is cleaved into smaller molecules by the addition of water. This process involves the breaking of chemical bonds through the insertion of water molecules, often resulting in the formation of new functional groups or the decomposition of larger molecules.
Infrared Spectroscopy: Infrared spectroscopy is an analytical technique that uses the infrared region of the electromagnetic spectrum to identify and characterize the chemical composition of a sample. It provides information about the molecular structure and functional groups present in a compound by analyzing the absorption or emission of infrared radiation.
Leaving Group Ability: Leaving group ability refers to the propensity of a functional group or atom to depart from a molecule during a chemical reaction. The ease with which a leaving group can be displaced is a critical factor in determining the reactivity and mechanism of various organic reactions.
Metabolic Pathways: Metabolic pathways are the series of interconnected chemical reactions that occur within cells to sustain life. These pathways are responsible for the breakdown, synthesis, and transformation of molecules, providing the energy and building blocks necessary for cellular function and organismal survival.
N-Acetylglucosamine: N-Acetylglucosamine (GlcNAc) is an amino sugar that is a key structural component of many biomolecules, including chitin, peptidoglycan, and glycoproteins. It is a derivative of glucose and plays crucial roles in various biological processes related to the chemistry of thioesters and acyl phosphates, which are important carboxylic acid derivatives.
NMR Spectroscopy: NMR (Nuclear Magnetic Resonance) spectroscopy is an analytical technique that uses the magnetic properties of atomic nuclei to provide detailed information about the structure and composition of organic compounds. It is a powerful tool for identifying and characterizing chemical compounds, particularly in the context of organic chemistry.
Nucleophilic Attack: Nucleophilic attack is a fundamental chemical reaction in which a nucleophile, an electron-rich species, attacks an electrophilic (electron-deficient) center, forming a new covalent bond. This process is central to understanding many organic reactions, including polar reactions, addition reactions, and substitution reactions.
Resonance Stabilization: Resonance stabilization is a phenomenon where the delocalization of electrons in a molecule or ion leads to a more stable configuration compared to a single Lewis structure. This concept is crucial in understanding the behavior and properties of various organic compounds, including their acidity, basicity, reactivity, and stability.
Thioester: A thioester is a functional group that consists of a carbonyl carbon connected to a sulfur atom instead of an oxygen atom, as in an ester. Thioesters are important biological carboxylic acid derivatives that play a crucial role in various metabolic processes and have unique reactivity compared to their oxygen-containing counterparts.
Thioester Hydrolysis: Thioester hydrolysis is the chemical process by which a thioester, a compound containing a sulfur-carbon-oxygen functional group, is cleaved by the addition of water to form a carboxylic acid and a thiol. This reaction is a key step in the metabolism of biological carboxylic acid derivatives.
Thioesterase: Thioesterase is an enzyme that catalyzes the hydrolysis of thioester bonds, which are found in various biological carboxylic acid derivatives such as thioesters and acyl phosphates. This enzyme plays a crucial role in the biosynthesis of fatty acids by regulating the length of the growing carbon chain.
Thioesters: Thioesters are organic compounds that are structurally similar to esters, but with a sulfur atom replacing the oxygen atom in the carbonyl group. They are an important class of carboxylic acid derivatives that have various applications in biological processes and organic synthesis.