The Organic Acids Profile (OAP) offered by US BioTek Laboratories provides an excellent overview of mitochondrial and primary biochemical functions. The analytes on the OAP can detect problems with the body’s processing of dietary macronutrients (carbohydrates, fats, and proteins) or problems with the Citric Acid Cycle (CAC), one of the primary pathways in the mitochondria.
The OAP also provides an overview of bacterial metabolism in the gastrointestinal microbiome, which can have profound effects on the health, and on biochemical and detoxification functions of the human host.
Recent scientific advances illuminate the importance of inheritance (genetic and epigenetic), environment and nutrition for human health and wellness. Pollution, malnutrition, or other physical or psychological stress can dysregulate or inhibit primary biochemical pathways, mitochondria, the gut microbiome, and detoxification functions. If an individual has inherited low-activity enzyme variants, such stressors may be enough to shift them from health to disease. Chronic inflammatory diseases such as type II diabetes, cardiovascular disease, fatty liver, immune system dysregulation, premature ageing, etc. have been associated with mitochondrial dysfunction and/or the dysregulation of primary biochemical pathways. The OAP is a reliable tool for screening and monitoring individuals with inherited or acquired biochemical or mitochondrial dysregulations.
US BioTek’s Organic Acids Profile is designed to screen the general population for metabolic problems associated with aging, chronic inflammation, environment-induced mitochondrial dysfunction, and low-activity enzyme variants requiring additional nutritional support. The test is not designed to diagnose inborn errors of metabolism (IEMs); the majority of IEMs result in significant functional and intellectual challenges and are diagnosed in infancy. Please note that, as with all urine tests, adequate kidney function is required for accurate results.
References:
- Cani PD. Interactions between gut microbes and host cells control gut barrier and metabolism. Int J Obes Suppl. 2016;6(Suppl 1):S28-S31.
- Dela Cruz CS, Kang MJ. Mitochondrial dysfunction and damage associated molecular patterns (DAMPs) in chronic inflammatory diseases. Mitochondrion. 2018;41:37-44.
- Hollman AL, Tchounwou PB, Huang HC. The Association between Gene-Environment Interactions and Diseases Involving the Human GST Superfamily with SNP Variants. Int J Environ Res Public Health. 2016;13(4):379.
- Jain A, Li XH, Chen WN. An untargeted fecal and urine metabolomics analysis of the interplay between the gut microbiome, diet and human metabolism in Indian and Chinese adults. Sci Rep. 2019;9:9191. https://doi.org/10.1038/s41598-019-45640-y
- Johannsen DL, Ravussin E. The role of mitochondria in health and disease. Curr Opin Pharmacol. 2009;9(6):780-786.
- Picard M, McEwen BS. Psychological Stress and Mitochondria: A Systematic Review. Psychosom Med. 2018;80(2):141-153.
- Tsoukalas D, Alegakis A, Fragkiadaki P, et al. Application of metabolomics: Focus on the quantification of organic acids in healthy adults. Int J Mol Med. 2017;40(1):112-120.
2-Hydroxyphenylacetate is a key intermediary in the metabolism of phenylalanine, an essential amino acid, and tyrosine, a conditionally essential amino acid. Elevated levels of 2-Hydroxyphenylacetate can signal underlying metabolic disturbances or genetic abnormalities in phenylalanine and tyrosine metabolism, such as phenylketonuria (PKU) or tyrosinemia. Monitoring 2-Hydroxyphenylacetate levels as part of the Organic Acids Profile can be instrumental in diagnosing and managing these metabolic disorders, facilitating early intervention and personalized treatment strategies for affected individuals.
2-Methylhippurate is a byproduct of detoxification of the common solvent xylene. Urinary excretion of 2-methylhippurate is a sensitive and specific marker for xylene exposure which increases oxidative stress. What is Xylene? Elevations indicate an exposure to this potentially toxic compound found in paint, varnishes, paint thinners, solvents, and many aerosols. Such exposures increase the burden on liver detoxification. An abundant supply of glycine (an amino acid) and vitamin B5 are important for removing xylene from the body. Sources of Xylene: - Automotive emissions: poor emission-control devices on older vehicles, poor maintenance practices, aviation fuel, waste and landfill sites, localized industrial discharges and spillage incidents, tobacco smoke. - Household: topical contact or inhalation of varnish/polishers, paint, paint thinner, paint remover, shellac, rust preventatives, lacquers, inks, dyes, adhesives, cleaning fluids, degreasing agents, household cleaning products. - Used as a solvent for rubbers, synthetic resins, gums, inks, paint. - Fabric and leather treatments. - Used in the synthesis of plasticizers and in the manufacture of polyester fiber, film, insecticide formulations, and perfumes. Industry: paint and printing ink industries, automobile body and related repairs, photographic processing, rubber, leather, plastics and textile industries, flooring contractor.
Benzoate, was one of the compounds first found to be elevated in urine from patients with intestinal bacterial overgrowth of various origins. Many people with intestinal bacterial overgrowth resulting from cystic fibrosis, unclassified enteritis, celiac disease, or short bowel syndrome have elevated benzoate along with varying degrees of elevated phenylacetate, p-hydroxybenzoate, and p-hydroxyphenylacetate. Benzoic acid, a common food component used as a preservative in packaged foods such as pickles and lunch meats, also occurs naturally in cranberries and other fruits, a factor to take into account when interpreting elevated hippurate levels in urine. Whether the source is dietary intake or jejunal bacterial metabolism, benzoate should be rapidly converted to hippurate by conjugation with glycine. What is Hippurate? Hippurate is produced by the conjugation of Benzoate and glycine, found as a normal component in urine as a metabolite of aromatic compounds from food. Increased urine hippuric acid content may have antibacterial effects. What is Glycine? Glycine is an amino acid serving several important purposes within the body, including: - Detoxification, - DNA formation, - The synthesis of hemoglobin, - and as a part of brain neurotransmission pathways. - In the liver, glycine helps to convert many potentially harmful substances, including toxic materials such as benzoic acid (benzoate) into harmless forms. References: – van der Heiden C, Wauters EA, Duran M, et al. Gas chromatographic analysis of urinary tyrosine and phenylalanine metabolites in patients with gastrointestinal disorders. Clin Chim Acta, 1971;34:289-296. – Temellini A, Mogavero S, Giulianotti PC, et al. Conjugation of benzoic acid with glycine in human liver and kidney: a study on the interindividual variability. Xenobiotica 1993;23:1427-1433.
Citrate holds significant importance in metabolic assessments and clinical evaluations. This molecule plays a central role in energy metabolism as it is an essential component of the Citric Acid Cycle (CAC), also known as the Krebs cycle, which is a crucial process in cellular respiration. Citrate serves as the starting point in the CAC, where it undergoes a series of enzymatic reactions to generate ATP, the cell's primary energy currency. Elevated citrate levels on the panel can provide valuable insights into the metabolic state of an individual. High citrate levels may indicate an overactive CAC, potentially stemming from an increased supply of precursor molecules like pyruvate and acetyl-CoA or a boost in metabolic demand for energy production. This can be associated with conditions such as increased physical activity or a high-carbohydrate diet. Conversely, low citrate levels could signify a compromised CAC, which may result from various factors, including enzyme inhibitions, nutrient deficiencies, or metabolic imbalances.
Ethylmalonate, together with Adipate and Suberate, gives information about your ability to process fatty acids. Ethylmalonate, which comes from the breakdown of butyrate, has a carnitine-dependent pathway and can accumulate with an insufficient amount of carnitine. Dietary fat, carbohydrate, and protein are all broken down to produce energy using pathways that require vitamin B2 (riboflavin). If you do not have sufficient riboflavin, compounds such as adipate, suberate, and ethylmalonate may increase in urine. What is Carnitine? Carnitine helps your body use fatty acids. The body makes small amounts of carnitine. However, if minimum requirements are not met, carnitine dependent functions fail to proceed normally. Long-chain fatty acids go through beta-oxidation in the mitochondria, which is a carnitine dependent step. If there are inadequate amounts of carnitine, the long-chain fatty acids will get processed outside of the mitochondria; Adipate and suberate are by-products of long-chain fatty acid breakdown outside of the mitochondria.
Citric acid, cis-aconitic acid, and isocitric acid are the first three metabolites in the Krebs Citric Acid energy production cycle, which operates in the mitochondria of your cells. Citrate, cis-Aconitate (and Isocitrate) are involved in both energy production and removal of toxic ammonia. High levels can indicate ammonia toxicity. Chronic loss of these valuable compounds can contribute to loss of organ reserve and disturbances in neurological function. If they are low they can indicate a need for essential amino acids, especially arginine.
Lactate serves as a valuable metabolic marker that provides insights into various physiological processes within the body. Elevated levels of lactate can signify multiple underlying factors, including impaired mitochondrial function, nutrient deficiencies, or metabolic disorders. Monitoring lactate levels on the panel aids healthcare practitioners in assessing energy metabolism, identifying potential issues with oxygen delivery and utilization, and recognizing conditions like lactic acidosis.
Mandelate is a Styrene metabolite. Sources of exposure: - Raw materials (benzene and ethylene) for the manufacture of styrene are supplied primarily from the petroleum industry. - Used in the manufacture of synthetic rubbers, synthetic latex, polyesters, and plastic products. - Automotive emissions, tobacco smoke, released from building materials, carpet backing. Low-level exposure may occure through ingestion of food products packaged in polystyrene containers. - Packaging materials, toys, hobbies, crafts, house wares and appliances, electrical and thermal insulation, fiberglass, pipes, automobile parts, foam cups. - Emissions from styrene production and disposal procedures - chemical spills, landfill sites and industrial discharges. - Occupational Exposure: industries and operations concerned with the fabrication and application of plastics - styrene/polystyrene manufacturing plants, resin manufacturers, synthetic rubber plants, boats and automobile plants, laminators. Effects: - Depression of the central nervous system. - Dizziness, lightheadedness, headache, drowsiness, nausea, impared balance, manual dexterity and reaction time, difficulty concentrating. - Irritation of mucous membranes, dermatitis, nausea, fatigue. - Genotoxic. Metabolism: Styrene is metabolized in the liver by cytochrome P-450 dependent multifunction oxidase enzymes, into its epoxide derivatives. The major metabolic pathway involves the sequential oxidation to mandelic and phylglyoxylic acids. Styrene oxides are also conjugated with glutathione. Styrene and its metabolites accumulate in lipid depots. Its slow elimination suggests the possibility for bioaccumulation from chronic exposure. The sum of the metabolites, mandelate and phylglyoxylate exhibit a higher correlation ratio than the separate levels of the analytes.
Methylsuccinate is a metabolite in the body's biochemical pathways and is primarily associated with the catabolism of certain amino acids, including methionine and threonine. Elevated levels of methylsuccinate can be indicative of metabolic disturbances related to amino acid metabolism. High methylsuccinate levels may stem from various factors, including enzyme deficiencies or genetic mutations in the pathways involved in methionine and threonine metabolism. Such elevations could be associated with conditions like methylmalonic acidemia, which is a group of rare genetic disorders affecting organic acid metabolism. Increased urinary methylsuccinate levels with: Diet - Fasting - Calorie-restricted diets - High-fat or -protein diets Medical conditions - Diabetes or metabolic syndrome - Impaired liver beta-oxidation - Obesity Decreased urinary methylsuccinate levels if: B12 deficiency - Ethylmalonate and methylmalonate may be high Low-fat or -protein diet Fat malabsorption
Para-hydroxyphenylacetate, often referred to as P-Hydroxyphenylacetate or PARA, is a diagnostic tool used in functional medicine and clinical assessments. PARA is a key intermediate in the degradation pathway of the amino acid tyrosine and is produced during the breakdown of tyrosine in the body. Elevated levels of PARA on the panel can provide valuable insights into various metabolic and enzymatic processes. An abnormal PARA level can be indicative of issues related to tyrosine metabolism, such as deficiencies in enzymes like phenylalanine hydroxylase or tyrosine aminotransferase. It can also suggest disruptions in gut microbiota, as some bacteria produce PARA as a metabolic byproduct.
Phenylglyoxylate is a Styrene metabolite. Sources of exposure: - Raw materials (benzene and ethylene) for the manufacture of styrene are supplied primarily from the petroleum industry. - Used in the manufacture of synthetic rubbers, synthetic latex, polyesters, and plastic products. - Automotive emissions, tobacco smoke, released from building materials, carpet backing. Low-level exposure may occure through ingestion of food products packaged in polystyrene containers. - Packaging materials, toys, hobbies, crafts, house wares and appliances, electrical and thermal insulation, fiberglass, pipes, automobile parts, foam cups. - Emissions from styrene production and disposal procedures - chemical spills, landfill sites and industrial discharges. - Occupational Exposure: industries and operations concerned with the fabrication and application of plastics - styrene/polystyrene manufacturing plants, resin manufacturers, synthetic rubber plants, boats and automobile plants, laminators. Effects: - Depression of the central nervous system. - Dizziness, lightheadedness, headache, drowsiness, nausea, impared balance, manual dexterity and reaction time, difficulty concentrating. - Irritation of mucous membranes, dermatitis, nausea, fatigue. - Genotoxic. Metabolism: Styrene is metabolized in the liver by cytochrome P-450 dependent multifunction oxidase enzymes, into its epoxide derivatives. The major metabolic pathway involves the sequential oxidation to mandelic and phylglyoxylic acids. Styrene oxides are also conjugated with glutathione. Styrene and its metabolites accumulate in lipid depots. Its slow elimination suggests the possibility for bioaccumulation from chronic exposure. The sum of the metabolites, mandelate and phylglyoxylate exhibit a higher correlation ratio than the separate levels of the analytes.
Pyruvate is a key player in energy metabolism, serving as a critical intermediate in the glycolytic pathway, where glucose is converted into pyruvate, and subsequently, pyruvate plays a central role in the Citric Acid Cycle (CAC), also known as the Krebs cycle. Elevated pyruvate levels on the panel can indicate a range of metabolic challenges and disruptions. High pyruvate levels may arise due to factors such as nutritional inhibitions affecting enzymes involved in pyruvate breakdown, the presence of low-activity enzyme variants inherited genetically, an abundance of precursor molecules like glucose and amino acids, or elevated levels of downstream products like lactate and citrate. These findings can signal potential issues with the entry of pyruvate into the CAC, affecting overall energy production and metabolism. Pyruvate's levels can also be influenced by various medical conditions, such as acidosis or chronic fatigue syndrome, which may further impact its metabolic functions. Additionally, pyruvate's interconversion with other metabolites, like lactate, can be compromised in cases of inadequate NAD+ synthesis or the presence of inherited enzyme variants with reduced activity, potentially necessitating vitamin B3 supplementation for improved NAD+ levels. Furthermore, understanding pyruvate's role in the context of environmental exposures, such as arsenic contamination and phthalate exposure, is crucial. Arsenic exposure can disrupt pyruvate metabolism and affect other organic acids, while phthalate exposure may inhibit the enzyme responsible for pyruvate-lactate interconversion. Overall, monitoring pyruvate levels on the US BioTek Organic Acids Panel aids healthcare practitioners in assessing metabolic health, identifying potential enzymatic deficiencies or imbalances, and guiding personalized interventions to optimize overall well-being.
