Amino Acid Metabolism

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Aspartate α-ketoglutarate Glutamate Pyruvate α-keto acid Amino acid (cytosol) Amino acids (extracellular) Aspartate Transaminase (AST) Alanine Transaminase (ALT) Transamination (Overview) Oxaloacetate Glutamate α-ketoglutarate Alanine Amino acid α-keto acid Aspartate Glutamine Oxaloacetate Amino acid Glutamate Ammonia (NH<sub>3</sub>) Amino acid α-ketoglutarate Glutamine synthase Glutamate Dehydrogenase Home Page

Amino Acid Metabolism

Amino acids are the components that make up proteins. There are 20 different amino acids, 9 of which cannot be synthesised by our body and are termed essential amino acids. These essential amino acids must come from the protein in the food we eat. Once protein has been digested and is broken down into individual amino acids, they are absorbed by enterocytes in the small intestine and released into the circulation. Most amino acids are taken up by the liver before being redistributed to other tissues.

Once taken up by a cell, amino acids have a number of metabolic fates. They can be used to synthesise new proteins. Alternatively, they can have their nitrogen group removed (in the form of ammonia) in a process called deamination. The resulting ammonia is eliminated as waste by the urea cycle (see Urea Cycle pathway), while the remaining hydrocarbon metabolite (termed α-keto acid) can then enter various metabolic pathways. The destination pathway depends on the type of keto acid, but can include oxidative pathways that produce ATP, such as the citric acid cycle (see The Citric Acid Cycle pathway), or biosynthetic pathways such as gluconeogenesis (see Gluconeogenesis pathway) or fatty acid synthesis (see Fatty Acid Synthesis pathway).

Key points:

Amino Acids (extracellular)

Extracellular amino acids comprise most of the free amino acid pool within our bodies. Amino acids from food are absorbed and redistributed by the liver throughout the body. The breakdown of body protein also supplies the amino acid pool and there is exchange of approximately 250g of amino acids per day between the free pool and body protein. Extracellular amino acids are taken up into cells by amino acid transporters in the plasma membrane. Twelve amino acid transporters have been identified to date, all with varying affinities for different amino acids.

Amino Acids (extracellular)

This amino acid is a substrate for a number of metabolic pathways. The transamination of alanine, which also involves α-ketoglutarate (an α-keto acid) as the nitrogen acceptor, produces pyruvate and glutamate. Pyruvate can be oxidised to form acetyl-CoA, which can enter the citric acid cycle (see The Citric Acid Cycle pathway), or be used for the synthesis of fatty acids (see Fatty Acid Synthesis pathway). Pyruvate can also be used as a substrate for gluconeogenesis (see Gluconeogenesis pathway).

Under conditions of prolonged energetic stress, such as during ultra-endurance exercise or extended fasting (or starvation), the rate of protein breakdown, particularly in skeletal muscle is increased. This provides amino acids, particularly alanine, as substrates for gluconeogenesis in the liver.

Key point:

Aspartate Transaminase (AST)

Aspartate transaminase (AST) catalyses the transamination of aspartate:

Aspartate + α-ketoglutarate → Oxaloacetate + Glutamate

The oxaloacetate produced is a citric acid cycle intermediate (see The Citric Acid Cycle pathway), but can also be used in the bypass reactions of gluconeogenesis (see Gluconeogenesis pathway). Elevated levels of AST in the plasma is often used as a biomarker of liver damage.

Glutamine

Glutamine is a non-essential amino acid that is important for protein synthesis, generation of ATP through oxidative pathways and as a nitrogen donor for biosynthetic processes including nucleotide synthesis. Glutamine is the most abundant free amino acid circulating in human plasma.

Glutamate

Glutamate is produced by the release of ammonia from glutamine via the enzyme glutamine synthase.

Glutamate is also a product of many transamination reactions such as alanine transaminase (ALT) and aspartate transaminase (AST). Glutamate also generates numerous other amino acids by donating its amino group to an α-keto acid. It also generates glutathione, an important reactive oxygen species buffering system.

Transaminases (Mitochondria)

The major transaminase localised to the mitochondria is aspartate transaminase (AST). It catalyses the interconversion of aspartate and α-ketoglutarate into glutamate and oxaloacetate.

The oxaloacetate produced is a citric acid cycle intermediate (see The Citric Acid Cycle pathway), but can also be used in the

bypass reactions of gluconeogenesis (see Gluconeogenesis pathway). AST in the plasma is often used as a biomarker of liver damage.

Glutamine synthase

Glutamine synthase (also known as Glutaminase) converts glutamine to glutamate in what is classified as a deamination reaction, producing ammonia (NH3) in the processes:

Glutamine + H2O → Glutamate + NH3

The free ammonia is used for biosynthetic processes such as nucleotide synthesis or consumed by the urea cycle for detoxification (see Urea Cycle pathway).

Glutamate Dehydrogenase

Glutamate dehydrogenase converts glutamate into α-ketoglutarate, also producing NADPH and ammonia (NH3) in the process:

Glutamate + H2O + NAD+ → α-ketoglutarate + NH3 + NADH

Release of ammonium from glutamate produces α-ketoglutarate, which is a citric acid cycle intermediate (see The Citric Acid Cycle pathway) that can be oxidised to produce ATP.

Transamination (Overview)

Transamination is any chemical reaction that transfers an amino group from an amino acid to an α-keto acid, to form a new amino acid and α-keto acid:

Amino acid + α-keto acid → α-keto acid + Amino acid

This is the major mechanism that coverts essential amino acids to non-essential amino acids and is also the pathway through which amino acids are ultimately deaminated.

Alanine Transaminase (ALT)

Alanine transaminase (ALT) catalyses the transamination of alanine:

Alanine + α-ketoglutarate → Pyruvate + Glutamate

It is one of the most common transamination reactions. The pyruvate produced has a number of potential metabolic fates. It can enter the citric acid cycle (see The Citric Acid Cycle pathway), be used as a substrate for gluconeogenesis (see Gluconeogenesis pathway) or be used for the synthesis of fatty acids (see Fatty Acid Synthesis pathway). ALT in the plasma is also often used as a biomarker of liver damage.

Alanine

This amino acid is a substrate for a number of metabolic pathways.

Under conditions of prolonged energetic stress, such as during ultra-endurance exercise or extended fasting (or starvation), the rate of protein breakdown, particularly in skeletal muscle is increased. This provides amino acids, particularly alanine, as substrates for gluconeogenesis (see Gluconeogenesis pathway) in the liver.

Key point:

Aspartate

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Amino acid (cytosol)

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Amino acid

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α-ketoglutarate

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α-keto acid

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Pyruvate

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Glutamate

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Oxaloacetate

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Ammonia (NH3)

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