The Vital Coenzyme Behind A-Keto Acid Decarboxylation

Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide. In organic chemistry, decarboxylation usually refers to the replacement of a carboxyl group with a hydrogen atom. The reverse process, which is the first chemical step in photosynthesis, is called carboxylation. The term decarboxylation is often associated with the loss of carbon dioxide from beta-keto acids. The coenzyme used for the decarboxylation of alpha-keto acids is thiamine pyrophosphate (TPP). TPP is a catalytic cofactor that creates a resonant stabilised imine-enamine anion upon binding with an alpha-keto acid.

Decarboxylation is the reduction of carbon

Decarboxylation is a chemical reaction that involves the removal of a carboxyl group and the release of carbon dioxide (CO2). This process typically occurs in carboxylic acids, where a carbon atom is eliminated from a carbon chain. Carboxylation, the addition of CO2 to a compound, is the reverse reaction and represents the initial phase of photosynthesis.

Decarboxylation is one of the oldest known organic reactions and is often associated with pyrolysis and destructive distillation. It is dependent on the stability of the carbanion synthon R-, although this anion may not be a true intermediate. Carboxylic acids, in general, undergo decarboxylation slowly. However, those with an α electron-withdrawing group, such as β‑keto acids, β‑nitriles, α‑nitro acids, or arylcarboxylic acids, tend to decarboxylate more easily.

Transition metal salts, especially copper compounds, facilitate decarboxylation through carboxylate complex intermediates. This process is integral to the malonic and acetoacetic ester syntheses. Decarboxylation is also observed in the biological context, where it is categorised based on the cofactors that catalyse the transformations. For instance, the decarboxylation of malonyl-CoA to acetyl-CoA is facilitated by biotin-coupled processes, while thiamine (T:) is essential for the decarboxylation of alpha-keto acids like pyruvate.

In the context of "which coenzyme is used for the decarboxylation of a-keto acids," thiamine (T) is the answer. It is the active component responsible for the decarboxylation of alpha-keto acids, as shown in the following reaction:

> T: + RC(O)CO2H → T=C(OH)R + CO2

> T=C(OH)R + R'COOH → T! : + RC(O)CH(OH)R'

Thiamine plays a crucial role in this process, ensuring the removal of the carboxyl group and the subsequent release of carbon dioxide from alpha-keto acids.

Transamination is the exchange of an amino group of an amino acid to a keto acid

Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). This reaction usually involves carboxylic acids, where a carbon atom is removed from a carbon chain.

Now, onto transamination: this is a chemical reaction that transfers an amino group to a keto acid to form new amino acids. This process is responsible for the deamination of most amino acids and is one of the major degradation pathways that convert essential amino acids to non-essential amino acids.

Transamination is accomplished by enzymes called transaminases or aminotransferases. α-ketoglutarate acts as the predominant amino-group acceptor and produces glutamate as the new amino acid. The amino group of glutamate is then transferred to oxaloacetate in a second transamination reaction, yielding aspartate.

Transamination catalysed by aminotransferase occurs in two stages. In the first stage, the α amino group of an amino acid is transferred to the enzyme, producing the corresponding α-keto acid and the aminated enzyme. During the second stage, the amino group is transferred to the keto acid acceptor, forming the amino acid product while regenerating the enzyme.

The chirality of an amino acid is determined during transamination. For the reaction to be completed, aminotransferases require the participation of an aldehyde-containing coenzyme, pyridoxal-5'-phosphate (PLP), a derivative of vitamin B6. The amino group is accommodated by the conversion of this coenzyme to pyridoxamine-5'-phosphate (PMP).

Transamination is a bimolecular reaction, and its mechanism is well known. First, the amino acid is bound to the active site to form a Schiff base with pyridoxal phosphate. Then, the α-amine group is separated by hydrolysis, and an α-keto acid, derived from the original amino acid, is formed and released. The prosthetic group of the enzyme is then converted into pyridoxamine phosphate. Subsequently, another α-keto acid enters the catalytic site as a second substrate, forming a Schiff base with pyridoxamine phosphate. The amine group is then transferred to the keto acid, pyridoxal phosphate is regenerated, and the newly formed amino acid is released.

Decarboxylation is one of the oldest known organic reactions

Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). It is one of the oldest known organic reactions, assumed to accompany pyrolysis and destructive distillation.

Decarboxylation usually refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carboxylation, the addition of CO2 to a compound.

The term "decarboxylation" typically means the replacement of a carboxyl group (-COOH) with a hydrogen atom. This reaction is almost irreversible because of the liberation of CO2.

Decarboxylation depends on the stability of the carbanion synthon R-, although the anion may not be a true chemical intermediate. Carboxylic acids with an α electron-withdrawing group (e.g. β‑keto acids, β‑nitriles, α‑nitro acids, or arylcarboxylic acids) decarboxylate easily.

Transition metal salts, especially copper compounds, facilitate decarboxylation via carboxylate complex intermediates.

Decarboxylation is also important in the malonic and acetoacetic ester synthesis, and the Knoevenagel condensation. It allows keto acids to serve as a stabilising protecting group for carboxylic acid enols.

Decarboxylation is also a significant process in biology, especially in glucose metabolism and amino acid conversion.

Biotin-coupled processes effect the decarboxylation of malonyl-CoA to acetyl-CoA

Biotin-coupled processes play a crucial role in the decarboxylation of malonyl-CoA to acetyl-CoA, a fundamental step in various biological processes. This reaction is catalysed by the enzyme acetyl-CoA carboxylase (ACCase), which exists in two forms: a heteromeric form found in most plant chloroplasts and bacteria, and a homomeric form found in plant cytosol, mammals, and fungi.

The heteromeric ACCase is composed of four subunits: biotin carboxyl transfer protein (BCCP), biotin carboxylase (BC), and α- and β-carboxyltransferases (CT). These subunits work together to mediate the carboxylation of acetyl-CoA to malonyl-CoA. The first step involves the ATP-dependent carboxylation of the biotin moiety, and the second step involves the transfer of the activated carboxyl group to acetyl-CoA to form malonyl-CoA.

The biotin-dependent carboxylation process is essential for the activity of ACCase. Biotin acts as a prosthetic companion of the enzyme, linked by an amide bond to the ε-amino group of a lysyl residue. This bond is formed by the enzyme biotin–apoprotein ligase. The carboxylation of biotin is then catalysed by the biotin carboxylase subunit, which is ATP-dependent and utilises bicarbonate as the CO2 donor.

The second half-reaction is performed by the carboxyltransferase subunit, which transfers the carboxyl group from carboxybiotin to acetyl-CoA, forming malonyl-CoA. This reaction is thermodynamically unfavourable but becomes spontaneous due to the hydrolysis of ATP.

The regulation of ACCase activity is crucial for maintaining proper metabolic function. Biotin attachment domain-containing (BADC) proteins are inactive analogs of biotin carboxyl transfer proteins that can displace the active subunits, downregulating ACCase activity. This feedback inhibition of ACCase by BADC proteins helps maintain a balance in fatty acid synthesis.

In summary, biotin-coupled processes are integral to the decarboxylation of malonyl-CoA to acetyl-CoA by facilitating the activity of the ACCase enzyme. This enzyme, in turn, plays a key role in fatty acid synthesis and other biological processes, making it a vital component of cellular metabolism.

Thiamine is the active component for decarboxylation of alpha-ketoacids

Thiamine, also known as thiamine pyrophosphate (TPP) or thiamine diphosphate (TDP), is a coenzyme that plays a crucial role in the decarboxylation of alpha-keto acids. TPP is the active form of the vitamin thiamine and acts as an important cofactor in biochemical processes.

The decarboxylation of alpha-keto acids, such as pyruvate, is a challenging reaction as it involves the generation of a carbanion on a carbonyl group, an intermediate not typically observed in carbonyl compound reactions. Thiamine pyrophosphate overcomes this challenge by stabilising the carbanion formed during the reaction. This stabilisation is achieved through the presence of adjacent sulfur and positively charged nitrogen atoms in the thiamine molecule.

The decarboxylation process can be non-oxidative or oxidative. In the non-oxidative decarboxylation of pyruvate, for example, the products are acetaldehyde and carbon dioxide. On the other hand, the oxidative decarboxylation of pyruvate yields acetate and carbon dioxide.

Thiamine pyrophosphate is essential in enzymatic reactions that involve decarboxylation, such as the pyruvate dehydrogenase complex (PDH complex). This complex is responsible for the decarboxylation of pyruvate, a crucial step in energy production in living organisms. Additionally, TPP plays a similar role in the alpha-ketoglutarate dehydrogenase complex, which converts 2-oxoglutarate (alpha-ketoglutarate) to succinyl CoA as part of the citric acid cycle.

The role of thiamine in decarboxylation reactions is not limited to the PDH complex and the alpha-ketoglutarate dehydrogenase complex. It is also involved in biosynthetic processes, particularly in the synthesis of certain amino acids. For instance, hydroxyethyl-TPP, derived from the TPP-assisted decarboxylation of pyruvate, is used in the biosynthesis of leucine, isoleucine, and valine.

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