Biochemistry in Medical Disciplines

substances, humans have slightly more than twenty that are in use in protein building or in the synthesis of neurotransmitters. L-tryptophan, for example, is an amino acid used to make serotonin. For this reason, some providers will give L-tryptophan to depressed patients to build serotonin levels.

Proteins and amino acids are the second largest molecular substance found in the human body. They can be classified according to their side chain, which can be aliphatic, acrylic, aromatic, or hydroxyl. Each side chain has a specific polarity that affects its solubility in aqueous solutions. The generic formulation of amino acids in humans is H2NCHRCOOH, where “R” refers to the side chain. All proteinogenic amino acids in humans are of the L-isomer type.

There are twenty standard amino acids that are coded for by at least one gene (there can be more than one gene for a protein). There are two non-standard amino acids with no gene that codes for them which are synthesize in other ways. Selenocysteine, for example, is encoded by a stop codon and an SECIS segment, not a gene. Pyrrolysine is another example of a non-standard amino acid.

Figure 2 shows the standard amino acids seen in nature:

Figure 2 Essential amino acids are not produced by the human body and must be consumed. There are nine of them and they include histidine, leucine, isoleucine, lysine, phenylalanine, methionine, threonine, valine, and tryptophan. Those that can be produced by the human body, including arginine, cysteine,

glutamine, glycine, proline, tyrosine, alanine, asparagine, aspartic acid, glutamic acid, and selenocysteine.

Besides tryptophan, there are two non-proteinogenic amino acids worth mentioning. Glutamic acid and GABA (gamma-amino-butyric acid) are neurotransmitters. Glutamic acid is the major excitatory amino acid in the central nervous system, while gamma-amino-butyric acid (GABA) is the main inhibitory amino acid in the central nervous system. Two other non-standard amino acids include glycine (which makes porphyrins in the body) and carnitine (which is necessary for lipid transport).

Amino acids have different structures that determine their solubility. The aromatic amino acids are phenylalanine, tyrosine, and tryptophan. The acidic amino acids are glutamic acid and aspartic acid. Glycine and alanine are considered “small amino acids” because of their short side chains. Basic amino acids include histidine, lysine, and arginine. Hydrophobic amino acids include valine, leucine, isoleucine, proline, and methionine. These do not dissolve well in water and are found on the inside of proteins— away from an aqueous environment. As in all of chemistry, slightly basic amino acids are attracted to slightly acidic amino acids. All of these side chains determine the protein shape.

Amino acids are crucial to protein synthesis. Peptides are short proteins that have different functions in the body. Longer chains of amino acids are called proteins. There are some peptides that are useful to know about in medicine. Insulin, vasopressin, human growth hormone, and gonadotropin releasing hormone are all well-established pharmaceutical-grade peptides used to treat different diseases. The most commonly prescribed peptide in medicine today is insulin. All therapeutic peptides must be given by non-oral means as they are degraded in the acidic environment of the stomach.

The process of converting amino acids into usable proteins or peptides in the body is called translation. On a cellular level this occurs in the ribosomes through the action of RNA (ribonucleic acid), which is translated from genes in the DNA of the nucleus. Transfer RNA or tRNA is the ribonucleic acid that puts the amino acids one-by-one on the terminal end of the peptide chain. This is where pyrrolysine and selenocysteine are made as they aren’t directly encoded for by a gene.

There are some ribosomal diseases caused by genetic defects that cause ineffective translation. These are rare syndromes that have varying phenotypes. Treacher-Collins syndrome is the most common “ribosomopathy”, leading to craniofacial abnormalities. Other known ribosomopathies are cartilage hair hypoplasia (anemia, dwarfism, hypoplastic hair), Schwachman-Diamond syndrome (neutropenia, pancreatic insufficiency, and short stature), 5q- Syndrome (macrocytic anemia and hypolobulated micromegakaryocytes), and Diamond Blackfan anemia (anemia, craniofacial abnormalities, short stature, and thumb abnormalities).

Non-proteinogenic amino acids are nearly as important clinically as proteinogenic amino acids. The main amino acids that are important in medicine that are non-proteinogenic include triiodothyronine, GABA, tryptophan, and L-dopa. Most of these are not directly encoded for by the DNA of the cell’s nucleus but are made by post-translational modification of existing amino acids. A few are made in the ribosomes themselves, while others are made by non-ribosomal peptide synthetases outside of the actual ribosome.