Thành viên:Naazulene/Phản ứng chuyển nhóm amino

Aminotransfer reaction between an amino acid and an alpha-keto acid

Phản ứng chuyển nhóm amino (tiếng Anh: transamination) là phản ứng chuyển nhóm amino vào ketoacid để tạo thành amino acid mới. Đây là con đường deamin của hầu hết amino acid, và cũng là một trong những con đường chuyển hóa chính để chuyển từ acid amin thiết yếu thành acid amin không thiết yếu (amino acid có thể được tổng hợp de novo trong sinh vật).

Những enzyme thực hiện phản ứng này được gọi chung là transaminase hoặc aminotransferase, và chất nhận amino chủ yếu là α-ketoglutarate, để tạo thành glutamate:

Aminoacid + α-ketoglutarate ⇌ α-keto acid + glutamate

Nhóm amino của glutamate sau đó được chuyển sang oxaloacetate để tạo aspartate:

Glutamate + oxaloacetate ⇌ α-ketoglutarate + aspartate

Cơ chế

Quá trình này bao gồm hai bước. Đầu tiên, enzyme nhận nhóm amino từ amino acid cho, sau đó là enzyme chuyển nhóm amino sang cho ketoacid nhận. Trung tâm lập thể của amino acid được quyết định trong hai bước này. Để phản ứng được hoàn thành, enzyme cần sự trợ giúp của một coenzyme là pyridoxal-5'-phosphate (PLP), một dẫn xuất của vitamin B6. Nhóm amino sẽ được đỡ bởi coenzyme này để tạo thành pyridoxamine-5'-phosphate (PMP). PLP.

Transamination catalyzed by aminotransferase occurs in two stages. In the first step, 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 complete, aminotransferases require participation of aldehyde containing coenzyme, pyridoxal-5'-phosphate (PLP), a derivative of Pyridoxine (Vitamin B₆). The amino group is accommodated by conversion of this coenzyme to pyridoxamine-5'-phosphate (PMP). PLP is covalently attached to the enzyme via a Schiff Base linkage formed by the condensation of its aldehyde group with the ε-amino group of an enzymatic Lys residue. The Schiff base, which is conjugated to the enzyme's pyridinium ring, is the focus of the coenzyme activity.

Ping Pong Bi Bi mechanism of PLP dependent enzyme catalyzed transamination. Aminotransferase reaction occurs in two stages consisting of three steps: Transimination, Tautomerisation and Hydolysis. In the first stage, alpha amino group of the aminoacid is transferred to PLP yielding an alpha ketoacid and PMP. In the second stage of the reaction, in which the amino group of PMP is transferred to a different alpha Ketoacid to yield a new alpha amino acid and PLP.

The product of transamination reactions depend on the availability of α-keto acids. The products usually are either alanine, aspartate or glutamate, since their corresponding alpha-keto acids are produced through metabolism of fuels. Being a major degradative aminoacid pathway, lysine, proline and threonine are the only three amino acids that do not always undergo transamination and rather use respective dehydrogenase.

Alternative Mechanism

A second type of transamination reaction can be described as a nucleophilic substitution of one amine or amide anion on an amine or ammonium salt. For example, the attack of a primary amine by a primary amide anion can be used to prepare secondary amines:

RNH₂ + R'NH⁻ → RR'NH + NH₂⁻

Symmetric secondary amines can be prepared using Raney nickel (2RNH₂ → R₂NH + NH₃). And finally, quaternary ammonium salts can be dealkylated using ethanolamine:

R₄N⁺ + NH₂CH₂CH₂OH → R₃N + RN⁺H₂CH₂CH₂OH

Aminonaphthalenes also undergo transaminations.^[2]

Types of aminotransferase

Transamination is mediated by several types of aminotransferase enzymes. An aminotransferase may be specific for an individual amino acid, or it may be able to process any member of a group of similar ones, for example the branched-chain amino acids, which comprises valine, isoleucine, and leucine. The two common types of aminotransferases are alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

References

• Smith, M. B. and March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 5th ed. Wiley, 2001, p. 503. ISBN 0-471-58589-0 • Gerald Booth "Naphthalene Derivatives" in Ullmann's Encyclopedia of Industrial Chemistry, 2005, Wiley-VCH, Weinheim. doi:10.1002/14356007.a17_009

Voet & Voet. "Biochemistry" Fourth edition

External links

• Amino Acid Biosynthesis Lưu trữ 2017-04-26 tại Wayback Machine
• The chemical logic behind aminoacid degradation and the urea cycle