To the layman, the words amino acids don’t ring a bell, and yet, we consume these special compounds every single day and they are present in almost everything we eat. Taking a closer look at the intricacies of what’s in our food, here is where I pay homage to protein, the macronutrient that most of us associate with muscles and strength (forget Popeye, shame on him for trying to fool us into believing that eating spinach would make you strong). To put things into simple perspective, amino acids are the building blocks of protein, and protein is involved in the repair and structural composition of just about every cell type in the human body. Additionally, given that humans are chemical factories, amino acids are also integral for the manufacturing of many endogenous compounds so it doesn’t take complicated mathematics to realize that inadequate protein intake will have deleterious health effects at some point, varying on the severity of deficiency.

Amino acids are grouped into two classes, essential and non-essential, referring to essential as needing to be obtained from the diet because their carbon skeletons cannot be synthesized de novo by animal cells or are insufficiently synthesized to meet metabolic requirements, whereas non-essential amino acids can be sufficiently synthesized endogenously. Deficiency in essential amino acids results in the increased oxidation of other amino acids because the utilization of other amino acids for protein synthesis becomes limited, and thus, all excessive amino acids become degraded in a tissue-specific manner (Hou & Wu, 2018).

The reason that amino acids participate in such a diverse spectrum of biochemical reactions is because all cell membranes, enzyme hormones, neurotransmitters (adrenaline, noradrenaline, serotonin, cortisol, acetylcholine, prostaglandins), antioxidant enzymes (catalase, glutathione peroxidase, ceruloplasmin), and gut hormones, such as ghrelin, leptin, cholecystokinin, incretins, brain-derived neurotrophic factor and insulin are made from amino acids (Takahashi et al, 2011).  Below is a list of the essential and non-essential amino acids in a table format, outlining the biochemical functions of each and to conclude, a list of symptoms associated with amino acid, or protein deficiency, is outlined. 

Essential	Non-essential
Histidine An important catalytic residue in many enzymes, such as trypsin, chymotrypsin, acetylcholinesterase, and blood-clotting cascade enzymes Participates in the hydroxylation of galactosylceramide, which is involved in the maintenance of myelin sheath by compacting myelin Chelates metals, such as copper, zinc, manganese, and cobalt Forms histamine (an important neurotransmitter that modulates inflammatory responses and gastric acid), urocanic acid (a metabolite that supports skin epithelial barrier formation), and muscle dipeptides, such as carnosine and anserine (Kessler & Raja, 2019)	Arginine Precursor to citrulline, an amino acid involved in detoxification metabolismActivates first step of ammonia detoxification in the urea cycle Stimulates insulin and growth hormone secretion (Blachier et al, 2013, p.92)   Through degradation by several enzymes, is as precursor to nitric oxide, polyamines, proline, glutamate, creatine and agmatine Essential for spermatogenesis, embryonic survival, foetal and neonatal growth, haemodynamics and maintenance of vascular tone (Takahashi et al, 2011)
Lysine Nitrogen/carbon precursor for ribo-/deoxyribonucleiotides (DNA/RNA synthesis) (Blachier et al, 2013, p.92)   Lysine, amongst the other essential amino acids, is required to maintain a positive nitrogen balance, which implies that if lysine is limited, then total protein synthesis will be limited and that causes an excess of other amino acids to be catabolized A precursor to glutamate via transamination, which in turn, produces acetyl-CoA (an intermediate of the energy-producing citric acid cycle)  (Matthews, 2020)	Cysteine Precursor to taurine (used for the conjugation of bile acids), glutathione (a potent antioxidant), pyruvate (intermediate in energy-producing cycles), coenzyme CoA (cofactor in many metabolic reactions) and hydrogen sulfide (a gas) (Blachier et al, 2013, p.104) Glutathione is composed of glycine, glutamate, and cysteine, with cysteine being the limiting step for glutathione synthesis in normal tissues. (Combs & DeNicola, 2019)  Given its sulfur content, cysteine is involved in disulfide bond formation, which contributes to the structural stability of proteins Cysteine residues in proteins can participate in redox reactions and act as ligands for metal ions, which are important processes for catalysing a variety of biochemical reactions and the function of metalloproteins (Bak et al, 2018)
Methionine Precursor to cysteine via transsulfuration of SAMe and then homocysteinePrecursor to SAMe, or S-adenosyl-methionine, which is a methyl donor (used in the synthesis of many endogenous compounds and methylation reactions), and glutathione (Stipanuk, 2004)	Glutamine Precursor (a-ketoglutarate) to intermediates of the TCA cycle (energy production) Nitrogen/carbon precursor for ribo-/deoxyribonucleiotides (DNA/RNA synthesis)  Precursor to ornithine, an amino acid involved in detoxification metabolism (Blachier et al, 2013, p.92)   Most abundant amino acid in human plasma and a source of nitrogen for biosynthesis of molecules, such as hexosamines, nucleotides, and non-essential amino acids (Choi & Coloff, 2019)
Phenylalanine Precursor to tyrosine via phenylalanine hydroxylase (Matthews, 2007) Also important for the synthesis of tyrosine’s derivatives, such as dopamine, norepinephrine and melanin (Schuck et al, 2015)	Tyrosine Transamination of tyrosine yields fumarate and acetoacetate, which are intermediates of the energy-producing citric acid cycle (Matthews, 2007) Metabolic pathways of tyrosine result in the production of dopamine, which is converted to noradrenaline, which in turn, is converted to adrenaline The precursor to dopamine, DOPA, is converted dopaquinone, and then it is converted to melanin (a component of skin pigment) Through a-ketoglutarate (carbon source from other amino acids) and glutamate, tyrosine can be converted in fumarate and acetoacetyl-CoA (intermediates of the energy-producing citric acid cycle) (Schuck et al, 2015)
Threonine·       Given the methyl group in its chemical structure, threonine proteins can participate in methylation reactions, influencing protein folding, and conformational adjustments (Barchi Jr. & Strain, 2023)	Glycine Along with proline, 4-hydroxyproline, and 3-hydroxyproline, glycine forms 33% of the composition of collagen, the major constituent of connective tissue (Krane, 2008)  Acts as a major inhibitory neurotransmitter of the ventral spinal cord and brain stem by binding to excitatory NMDA receptors (Kölker, 2018) Precursor to serine via transamination (Wu et al, 2020)
Tryptophan Generates chorismate, a precursor to aromatic amino acid synthesis via the Shikimate pathway Precursor to vitamin B3 (via kynurenine pathway) and 5-hydroxytryptophan, a precursor to serotonin (neurotransmitter involved in mood regulation, gastrointestinal function and vsoconstriction) and melatonin (a hormone involved in the wake-sleep cycle) Forms tryptophan tryptophylquinone (TTQ), a co-factor for amine dehydrogenase enzymes that degrade methylamine, which enables prokaryotes to use methylamine as a source of carbon, nitrogen, and energy (Barik, 2020)	Proline·       Due to its cyclic shape, it allows for variability in protein structure, such as collagen, for example, contains large amounts of proline and is important for the structural elements of the extra cellular matrix (Krane, 2008)
Isoleucine – refer to BCAAs below	Serine Central to the functioning of the nervous system by participating in the synthesis of nucleotides, phospholipids, proteins, and the neurotransmitters, glycine and d-serine (Kölker, 2018)  Provides carbon for on-carbon metabolism, which is involved in the synthesis of purines and pyrimidines (compounds integral to DNA/RNA structure), co-factors such as NADPH (antioxidant coenzyme), NADH and ATP, and SAMe (methyl donor in methylation reactions) (Wu et al, 2020)
Leucine – refer to BCAAs below	Alanine·       Serves as a substrate for gluconeogenesis (synthesis of glucose from protein), as alanine and alpha-ketoglutarate are converted (by alanine transaminase) into pyruvate and glutamate (Blachier et al, 2013, p.103)
Valine  – refer to BCAAs below	Asparagine Through asparagine synthetase, aspartate and glutamine, which is very abundant in the liver, is converted to asparagine, which can protect hepatocytes from cellular death during acute liver injury (Sun et al, 2023) Immunomodulatory properties by potentiating B cells, monocytes, natural killer cells, leukocytes, and CD8+ T-cell activity and subsequently, production of interferon-y (activates macrophages to increase phagocytosis), tumour necrosis factor-a (signalling molecule that orchestrates necrosis or apoptosis), and granzyme B (mediates apoptosis). (Wu et al, 2021)
	Aspartic acid  Precursor to intermediates of the TCA cycle Nitrogen/carbon precursor for ribo-/deoxyribonucleiotides (DNA/RNA synthesis) (Blachier et al, 2013, p.92)
	Glutamic acid  Precursor (a-ketoglutarate) to intermediates of the TCA cycle (Blachier et al, 2013, p.92)  Synthesized from glutamine via glutaminase (enzymes) and is important for the synthesis of non-essential amino acids, such as proline, aspartate, alanine, and serine, which are used for cysteine, glycine, asparagine and arginine synthesis (Choi & Coloff, 2019)   The most abundant amino acid in nature and a major taste component of dietary protein, which is referred to as “umami” Signals to regulate protein intake and evokes the cephalic phase of digestion (Takahashi et al, 2011)

Branched chain amino acids 

From the essential amino acids, there are three branched chain amino acids, leucine, isoleucine, valine, which are unique in comparison to the other amino acids because they are primarily oxidized in peripheral tissue, such as skeletal muscle, whereas other amino acids are oxidized in the liver. The ratio of abundance of each BCAA is approximately 1.6:2.2:1.0, Valine:Leucine:Isoleucine, which reflects the linked nature of their synthesis and oxidation (Neinast et al, 2019). BCAAs play a central role in regulating the rate of protein synthesis in skeletal muscle and other organs because when BCAAs undergo transamination in cells, keto acids are produced, which are then metabolized in acyl-CoA derivatives that enter the citric acid cycle (a metabolic process that produces energy) and the enzymes responsible for this process are mostly located in skeletal muscle, the heart, kidneys, and to a lesser extent, the liver.

BCAAs can be more energy effective than glucose, as oxidation of leucine produces more energy than glucose, in the form of ATP (adenosine triphosphate). Leucine also accelerates protein synthesis by activating the mTOR (mammalian target of rapamycin) pathway, which regulates protein synthesis amongst other functions. Additionally, BCAAs can enhance glycogen synthesis and facilitate glucose uptake by the liver and skeletal muscle, as glycogenesis occurs primarily in the liver and muscles (Monirujjaman & Ferdouse, 2014). 

Symptoms and long-term consequences of essential amino acid deficiency include (within the context of a holistic assessment and confirmation of protein deficiency);

• Low appetite and vomiting
• Impaired transport, absorption, and storage of organic/inorganic nutrients
• Impaired neurotransmitter synthesis
  • Psycho-emotional disorders
    • Anxiety, depression, moodiness, irritability
• Insomnia
• Reduced oxygen transport 
• Endocrine imbalance
  • Reduced concentrations of insulin, growth hormone, insulin-like growth factor 1, and thyroid hormones
• Growth stunting and impaired development in the young
• Physical fatigue and muscle wasting 
• Libido loss and reduced spermatogenesis
• Impaired antioxidative reactions (increased oxidative stress)
  • Impaired immune responses and advanced aging (Hou & Wu, 2018)   

References

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Barchi Jr., J.J., & Strain, C.N. (2023). The effect of methyl group on structure and function: serine vs. threonine glycosylation and phosphorylation. Frontiers in molecular biosciences, 10, 1117850. https://doi.org/10.3389/fmolb.2023.1117850

Barik, S. (2020). The uniqueness of tryptophan in biology: properties, metabolism, interactions and localization of proteins. International journal of molecular sciences, 21(22), 8776. https://doi.org/10.3390/ijms21228776

Blachier, F., Wu, G., & Yin, Y. (Eds.). (2013). Nutritional and physiological functions of amino acids in pigs. Springer. https://doi.org/10.1007/978-3-7091-1328-8

Choi, B., & Coloff, J.L. (2019). The diverse functions of non-essential amino acids in cancer. Cancers, 11(5), 675. https://doi.org/10.3390/cancers11050675

Combs, J.S., & DeNicola, G.M. (2019). The non-essential amino acid cysteine becomes essential for tumor proliferation and survival. Cancers, 11(5), 678. https://doi.org/10.3390/cancers11050678

Hou, Y., & Wu, G. (2018). Nutritionally essential amino acids. Advances in nutrition, 9(6), 849-851. https://doi.org/10.1093%2Fadvances%2Fnmy054

Kessler, A.T., & Raja, A. (2019). Biochemistry, histidine. StatPearls publishing. https://europepmc.org/article/nbk/nbk538201#free-full-text

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Kölker, S. (2018). Metabolism of amino acid neurotransmitters: the synaptic disorder underlying inherited metabolic diseases. Journal of inherited metabolic diseases, 41(6), 1055-1063.  https://doi.org/10.1007/s10545-018-0201-4

Krane, S.M. (2008). The importance of proline residues in the structure, stability and susceptibility to proteolytic degradation of collagens. Amino acids, 35(4), 703-710. https://doi.org/10.1007/s00726-008-0073-2

Matthews, D.E. (2020). Review of lysine metabolism with a focus on humans. The journal of nutrition, 150(1), 2548s-2555s. https://doi.org/10.1093/jn/nxaa224

Monirujjaman, Md., & Ferdouse, A. (2014). Metabolic and physiological roles of branched-chain amino acids. Advances in molecular biology, 2014. https://doi.org/10.1155/2014/364976

Neinast, M., Murashige, D., & Arany, Z. (2019). Branched chain amino acids. Annual review of physiology, 81, 139-164. https://doi.org/10.1146%2Fannurev-physiol-020518-114455

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Wu, Q., Chen, X., Li, J., & Sun, S. (2020). Serine and metabolism regulation: a novel mechanism in antitumor immunity. Aging and disease, 11(6), 1640-1653. https://doi.org/10.14336%2FAD.2020.0314