Amino acid Deficiencies and Supplementation

In many diseases and during undernutrition diminished turnover of amino acids can occur. These deficiencies may concern specific amino acids in certain diseases or a more generalized amino acid deficiency. The resulting functional deficits can contribute to the symptoms, severity, and progress of the disease. In some instances these deficits can be counteracted by simple supplementation of the deficient amino acids. Amino acid supplementation is also applied to enhance turnover and improve amino acid function in nondeficient patients. However, amino acid supplementation in nondefi-cient states does not necessarily lead to an increased function since the organism utilizes what is programed by regulating hormones and cytokines. An additional factor to consider is that metabolic processes can be subject to counter-regulatory feedback mechanisms. Some important metabolic processes served by a specific amino acid require only a marginal part of the total flux of that amino acid. The question may be raised whether true shortages may arise in such pathways, and supplemented amino acids may be

Table 1 Specific functions of amino acids and their intermediate products

Amino acid

Intermediate products Function

Supplementation efficacy

Alanine Pyruvate

Arginine Nitric oxide

Urea

Creatine

Agmatine

Citrulline Ornithine

Proline

Asparagine

Aspartic acid Methionine

Cysteine

(Cystine)

Glutamic acid

Glutamine

Glycine

Serine

Threonine

Histidine Lysine

Arginine production Polyamines

Hydroxyproline

Oxaloacetate, fumarate

Creatine Glutathione

Taurine

Glutamine a-ketoglutarate Glutathione 7-aminobutyric acid

Ammonia

Purines, pyrimidines

Glutathione Creatine

Glycine

Serine

Histamine

Carnitine

Glutamate

Branched chain amino acids Isoleucine a-keto-p-methylvaleric acid

Leucine a-ketoisocaproic acid

Gluconeogenesis Nitrogen transport Vasodilation Immunomodulation Neurotransmission

Ammonia detoxification Muscle constituent/fuel Cell signaling Ornithine precursor

Cell differentiation Proline precursor

Hepatocyte DNA, protein synthesis Collagen synthesis Aspartic acid precursor

Gluconeogenesis Cysteine precursor (see arginine) Antioxidant

Bile acid conjugation, neuronal cell development, regulation of membrane potential, calcium transport, antioxidant

Ammonia disposal Gluconeogenesis Antioxidant Inhibition CNS

Excitation CNS (NMDA receptor) Inter-organ nitrogen transport

Renal HCO3 production

RNA synthesis, DNA synthesis

Glutamic acid precursor

Inhibition CNS (glycine receptor)

Excitation CNS (NMDA receptor)

Antioxidant

(see arginine)

Serine precursor

Excitation CNS (NMDA receptor)

Glycine precursor

Cysteine precursor

Brain development

Immunomodulation Gastric acid secretion Mitochondrial oxidation of long-chain fatty acids

Important in regulation of energy and protein metabolism Substrate for glutamine synthesis

Data too limited

Positive effects of arginine-containing immunonutrition on morbidity in surgical and trauma patients suggested; further research required

Improves healing of burns (ornithine a-ketoglutarate)

(Asparaginase-induced asparagine depletion is therapeutic in leukemia)

Improves antioxidant status in undernutrition, inflammatory diseases Reduces contrast-induced nephropathy in renal failure Mucolysis, symptom reduction in COPD Hepatoprotective in acetaminophen intoxication

Reduces infectious morbidity in trauma patients, burn patients, and surgical patients

Adjuvant to antipsychotics, probably reduces negative symptoms of schizophrenia

Adjuvant to antipsychotics, probably reduces negative symptoms of schizophrenia

Reduces chronic stress-induced anxiety

Upper gastrointestinal hemorrhage

Improve protein malnutrition and restore amino acid and neurotransmitter balance in hepatic failure and hepatic encephalopathy (supplemented BCAA)

Valine a-ketoisovaleric acid

D-serine

Table 1 Continued

Amino acid

Intermediate products Function

Supplementation efficacy

Aromatic amino acids Phenylalanine

Tyrosine

Tryptophan

L-dopa Dopamine

Noradrenaline, adrenaline

Tri-iodothyronine, thyroxine Kynureninic acid

Quinolinic acid Serotonin

Melatonin

Tyrosine precursor Dopamine synthesis

Movement, affect on pleasure, motivation

Activation of sympathetic nervous system (fight-or-flight response) Regulation of basal metabolic rate

CNS inhibition

CNS excitation

Mood regulation

Sleep regulation

Intestinal motility

Regulation of circadian rhythms

Possible slight improvement of cognitive functions after physical or mental exhaustion. Metabolites are powerful pharmacotherapeutic drugs

No scientific evidence for beneficial effects of supplementation

Different fonts indicate: nonessential amino acids, essential amino acids, and conditionally essential amino acids.

disposed of in pathways other than those serving to improve a specific function.

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