Amino Acids and Their Functions

Amino Acid Metabolism

• Amino acids are categorized as essential or non-essential
• Essential amino acids must be obtained from the diet, while non-essential amino acids can be synthesized by the body.
• Amino acids can be used as energy sources.
• Some amino acids are glucogenic (converted to glucose), others are ketogenic (converted to ketone bodies).
• Amino acid degradation (catabolism) involves transamination and oxidative deamination to remove the amino group.
• The resulting nitrogen is converted to urea and excreted, while the carbon skeleton enters the TCA cycle.
• Pyridoxal phosphate is an essential cofactor for transaminases which transfer amino groups.
• Transaminases are enzymes involved in amino acid degradation and are useful clinical markers of tissue damage.
• Genetic defects in amino acid metabolism can lead to serious diseases, with phenylketonuria (PKU) being a common example, particularly in Ireland.
• Methionine breakdown can produce homocysteine, a risk factor for heart disease.
• Amino acid breakdown generates ammonia and urea.
• Adequate intake of amino acids is crucial for health, even more so in cases of disease.
• Amino acids can't be stored long term in the body.

Amino Acid Structure

• Amino acids have a central carbon atom (α-carbon) bonded to an amino group (NH₃⁺), a carboxyl group (COO⁻), a hydrogen atom, and a variable R-group (side chain).
• This R-group differentiates the various amino acids.
• Examples of amino acids mentioned are Serine (Ser, S), Alanine (Ala, A), Phenylalanine (Phe, F) and Leucine (Leu, L).

Essential and Nonessential Amino Acids

• Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, and Valine are essential amino acids.
• Alanine, Arginine, Asparagine, Aspartate, Cysteine, Glutamate, Glutamine, Glycine, Proline, Serine, and Tyrosine are nonessential amino acids.
• Beans are low in methionine, and many cereal crops are very low in lysine.

Examples of Importance of Amino Acid Metabolism in Medicine

• Genetic defects in amino acid metabolism lead to various medical conditions, e.g. phenylketonuria (PKU).
• Elevated homocysteine levels are a risk factor for heart disease.
• Amino acid degradation generates ammonia and urea; toxicity can result from a build-up.
• Nutritional factors, and the need for adequate amino acids are important in health and in disease.

Amino Acid Degradation (Catabolism)

• Amino acids are degraded under three metabolic conditions following protein-rich meal ingestion, cellular protein turnover and starvation.
• Amino acid degradation involves removing the amino group to generate energy or to convert to glucose or ketone bodies.
• The carbon skeleton of amino acids enters the TCA cycle.
• Transamination, and oxidative deamination are involved in removing the amino group.

Classification of Amino Acids

• Amino acids are classified as glucogenic or ketogenic based on their metabolic fate.
• Glucogenic amino acids can be converted to glucose, while ketogenic amino acids lead to the formation of ketone bodies.
• Examples of both glucogenic and ketogenic amino acids are given in a table.

Inborn Errors of Amino Acid Metabolism

• Genetic defects in amino acid metabolism can lead to deficiencies in enzyme function.
• Inborn errors of metabolism can cause a build-up of toxic metabolites, and result in severe diseases such as PKU, Homocystinuria, and Alkaptonuria.
• Disorders often cause mental retardation or other serious clinical problems.
• Some disorders are more common in certain populations.

Phenylketonuria (PKU)

• PKU is caused by a genetic defect in phenylalanine hydroxylase, resulting in the inability to convert phenylalanine to tyrosine.
• This leads to a buildup of phenylalanine and its by-products.
• PKU is often treated with a low phenylalanine diet.
• Untreated PKU can cause significant developmental problems, particularly intellectual disability.
• All newborns are screened for PKU.

Alkaptonuria

• Alkaptonuria is caused by a deficiency in homogentisate oxidase.
• This leads to accumulation of homogentisic acid.
• Symptoms include dark urine and arthritis development.
• The buildup of homogentisic acid in the body also results in the production of dark pigments in body tissue and bones.

Homocystinuria

• Homocystinuria is a genetic disorder involving elevated homocysteine levels.
• It results from defects in the enzymes responsible for converting homocysteine to cysteine or methionine.
• Deficiencies in vitamin B6, folate, or vitamin B12 can also contribute to homocysteine build-up.
• Elevated homocysteine is a risk factor for premature arterial diseases, mental retardation, ectopic lentis (displacement of the lens of the eye) and skeletal abnormalities.

Additional Notes

• Many of the listed metabolic pathways are complex and require further in-depth study to fully understand all the nuances and details.
• The use of diagrams and chemical structures to illustrate the metabolic steps is vital for understanding the process.