Transferring Amino Groups from Primary Nitrogen Acceptors

• Initial Stage: Ammonia is introduced to biological pathways via primary nitrogen acceptors such as glutamate or α-ketoglutarate.

• Next Step: Transfer of amino groups from these acceptors to other molecules, primarily amino acids, which are then utilized for protein synthesis or as precursors for nitrogen-containing compounds.

Structure of α-amino and α-keto Acids

• Definitions:

  • α-amino Acids: Molecules containing an amino group attached to the α-carbon.

  • α-keto Acids: Molecules containing a keto group attached to the α-carbon.

• Interconversion: α-amino acids and α-keto acids can be interconverted by exchanging functional groups on the α-carbons, facilitated by Transaminases (enzymes).

Deamination and Amination Processes

• Transaminase Reactions: Facilitate the transfer of amino groups from amino acids to α-keto acids, converting them into α-amino acids.

  • Definition:

    • Amination: The process of adding an amino group (gains amino).

    • Deamination: The process of removing an amino group (loses amino).

Role of Glutamate in Amino Group Transfer

• Source of Amino Groups: Glutamate is primarily used to provide amino groups in transaminase reactions.

  • Generic Representation:

    • α-keto acid + Transaminase → α-amino acid + α-ketoglutarate.

Formation of Alanine from Pyruvate

• Example Reaction: Glutamate transfers its amino group to pyruvate to form alanine (an α-amino acid) and regenerate α-ketoglutarate.

Plant Mechanism for Glutamate Maintenance

• Challenge for Plants: Unlike certain bacteria, plants cannot readily regenerate glutamate from NH3 due to ammonia toxicity.

• Solution: Plants utilize a reductive amination reaction catalyzed by Glutamate Synthase to produce amino acids and maintain glutamate levels sufficiently.

• Process:

  1. Glutamate assimilates ammonia forming glutamine.

  2. Glutamate Synthase enables formation of two glutamate molecules from α-ketoglutarate and glutamine.

Synthesis of Amino Acids

• General Concepts:

  • Amino acid synthesis pathways vary; not all can be synthesized by all organisms.

  • Essential amino acids must be acquired through diet.

• Amino Acids from TCA Cycle Intermediates:

  • Several amino acids derive from TCA cycle intermediates, notably oxaloacetate.

Synthesis of Serine and Glycine

• Pathway Overview:

1. Serine is synthesized from the glycolysis intermediate 3-phosphoglycerate.

2. The transformation involves:

   • Oxidation of the α-carbon hydroxyl to a ketone.

   • Amino group addition via the enzyme phosphoserine transaminase, using glutamate as an amino group donor.

3. Removal of the phosphoryl group converts phosphoserine to serine.

4. Glycine is derived by replacing the hydroxymethyl group with a proton.

Synthesis Pathways of Aspartate and Asparagine

• Aspartate Formation: A simple transamination reaction converts oxaloacetate (α-keto acid) to aspartate (α-amino acid).

• Asparagine Formation: The enzyme asparagine synthetase facilitates the transfer of an amido group from glutamine to aspartate, forming asparagine.

Amino Acid Catabolism

• Degradation of Amino Acids: Involves three scenarios:

  1. Excess supply from diet (not stored).

  2. Normal cellular turnover of proteins.

  3. Starvation, which breaks down proteins for energy or glucose precursors.

• Generally, amino acids are degraded in the liver.

Summary of Amino Acid Degradation

• Continuous Pathways:

  1. Removal of α-amino groups (transamination and deamination).

  2. Fate of carbon skeletons, converted into TCA cycle intermediates.

• Transamination and Deamination:

  • Transaminases create a pool of glutamate.

  • Glutamate dehydrogenase deaminates glutamate, funneling groups into the urea cycle.

Carbon Skeleton Fate and Metabolism

• Carbon skeletons from amino acids are converted into metabolic intermediates:

  • α-ketoglutarate

  • Succinyl CoA

  • Fumarate

  • Oxaloacetate

  • Pyruvate

  • Acetyl CoA

• Glucogenic vs. Ketogenic Amino Acids: Majority are glucogenic, contributing to gluconeogenesis during starvation, whereas ketogenic amino acids can generate ketone bodies and energy.