Amino Acid Metabolism: An Overview

Amino Acid Metabolism

• Amino acids are substrates for protein synthesis.
• Amino acids provide nitrogen for synthesizing nitrogen-containing compounds like purines and pyrimidines.
• Amino acids can be catabolized to provide energy.

Classification of Amino Acids

• Chemical classification is based on the chemistry and polarity of side chains.
• Nutritional classification distinguishes between essential and non-essential amino acids.
• Metabolic classification categorizes amino acids as glucogenic, ketogenic, or both.

Overview of Amino Acid Metabolism

• Dietary proteins and body proteins contribute to the amino acid pool.
• Synthesis of non-essential amino acids also feeds into the amino acid pool.
• From the amino acid pool, amino acids can be used to synthesize body proteins and specified products.
• Keto-acids (carbon skeletons) are derived from the amino acid pool.
• Keto-acids can be converted into glucose (glucogenic) or ketones (ketogenic).
• Ammonia is removed from the amino acid pool, and converted to urea.
• Specified products include heme, hormones, creatine, melanin, and nitric oxide.

Degradation of Amino Acids

• Proteins are broken down by proteases like pepsin and trypsin.
• Amino acids absorbed from the intestine are carried to the liver via the portal blood.
• Liver cells process the amino acids.
• Tissue proteins are continually disintegrated, releasing amino acids into circulation.
• Amino acids from all sources combine to form the "general amino acid pool".
• Total amino acid concentration in the blood is 30-100 mg/100 ml.
• Amino acid N2 concentration in the blood is 4-5 mg/100 ml.

Removal of Nitrogen from Amino Acids

• The first step in catabolism is the removal of the α-amino group.
• Removed nitrogen can be incorporated into other compounds or excreted.
• Amino groups are removed or replaced through transamination and oxidative deamination.

Transamination

• Transamination involves the transfer of α-amino groups to α-keto glutarate.
• The products of transamination are α-keto acids and glutamate.
• α-keto glutarate plays a unique role by accepting amino groups and becoming glutamate.
• Glutamate produced by transamination can be oxidatively deaminated or act as an amino group donor for non-essential amino acid synthesis.
• Aminotransferases catalyze the transfer of amino groups from one carbon skeleton to another.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) catalyze the two most important aminotransferase reactions.

Alanine Aminotransferase (ALT)

• ALT is also known as glutamate pyruvate transaminase (GPT or SGPT).
• Present in many tissues, ALT catalyzes the transfer of the amino group of alanine to α-keto glutarate.
• This transfer results in the formation of pyruvate and glutamate.

Aspartate Aminotransferase (AST)

• AST is also known as glutamate oxaloacetate transaminase (GOT or SGOT).
• During amino acid catabolism, AST transfers amino groups from glutamate to oxaloacetate, forming aspartate.

Oxidative Deamination

• Unlike transamination, oxidative deamination results in the liberation of amino groups as free ammonia.
• These reactions primarily occur in the liver and kidney, producing α-keto acids and ammonia.

Glutamate Dehydrogenase

• Amino groups from most amino acids are funneled to glutamate by transamination with α-keto glutarate.
• Glutamate is unique because it is able to undergo rapid oxidative deamination.
• Glutamate dehydrogenase catalyzes this reaction.

Urea Formation

• Excess ammonia derived from amino acid catabolism is removed by producing urea, which is then excreted in the urine.

Decarboxylation Reaction

• Decarboxylation is the reaction by which CO2 is removed from the COOH group of an amino acid, resulting in the formation of an amine.
• The enzyme decarboxylase catalyzes this reaction.
• Tissues like the liver, kidney, and brain possess the enzyme decarboxylase.
• Products of decarboxylation of some amino acids include:
  • Tyrosine to tyramine
  • Tryptophan to tryptamine
  • Histidine to histamine
  • Glutamic acid to γ-aminobutyric acid

Amino Acid Metabolism and Central Metabolic Pathways

• 20 amino acids are converted to 7 products: pyruvate, acetyl-CoA, acetoacetate, α-ketoglutarate, succinyl-CoA, oxaloacetate, and fumarate.

Biosynthesis of Amino Acids

• Amino acid synthesis refers to the biochemical processes (metabolic pathways) by which amino acids are produced from other compounds.
• The substrates for these processes are various compounds in the organism's diet.
• Humans can synthesize only 12 of the 20 standard amino acids.

Non-Essential Amino Acid Biosynthesis: Glutamate and Aspartate

• Glutamate is synthesized from its α-keto acid precursor through a simple 1-step transamination reaction catalyzed by glutamate dehydrogenase.
• Aspartate is synthesized by a transamination reaction catalyzed by AST.

Muscle Alanine Production

• Muscle alanine is produced either directly from protein degradation, or from the transamination of pyruvate by alanine transaminase (ALT, also referred to as serum glutamate-pyruvate transaminase, SGPT).

Cysteine Biosynthesis

• Serine and homocysteine via cystathionine synthase and lyase.

Tyrosine Biosynthesis

• Tyrosine is produced in cells by hydroxylating the essential amino acid phenylalanine, using phenylalanine hydroxylase.

Serine Biosynthesis

• The main pathway to de novo biosynthesis of serine starts with the glycolytic intermediate 3-phosphoglycerate.

Glycine Biosynthesis

• The main pathway to glycine is a 1-step reversible reaction catalyzed by serine hydroxymethyltransferase (SHMT).