Targeted Assays

Bile acids are derived from cholesterol and serve an important role in emulsifying and digesting lipids. In addition, their metabolism is intimately involved with the microbiota and they have been shown to exhibit endocrine and metabolic activity via receptors like FXR and TGR5.

The Bile Acid Panel measures all of the major human and rodent primary and secondary bile acids as well as their glycine and taurine conjugates.

7-α-Hydroxy-4-cholesten-3-one (C4) is an intermediate in the biosynthesis of bile acids from cholesterol. The precursor to C4 is 7α-hydroxycholesterol which is produced from cholesterol via the hepatic enzyme, 7α-hydroxylase. 7-α-hydroxylase catalyzes the rate-limiting step in bile acid synthesis and its activity is tightly regulated via the FXR receptor. Measurement of the stable metabolite C4, a product of the next oxidative enzymatic reaction after 7-α-hydroxylase, is reflective of hepatic de-novo bile acid synthesis and FXR receptor activation. Bile acid malabsorption is associated with a variety of gastrointestinal pathologies (e. irritable bowel syndrome, ileal disease) and is characterized by elevated serum C4 levels.

Central carbon metabolism involves enzymatic conversion of sugars into metabolic precursors that are used to generate the entire biomass of the cell. The metabolites in this panel include key citric acid cycle compounds that connects carbohydrate, fat, and protein metabolism. In addition to supplying key metabolic precursors, central carbon metabolism is used to oxidize simple sugar molecules obtained from food to supply energy to living systems. Measurement of central carbon metabolites has great industrial relevance since it may allow engineering of selected metabolic steps to optimize carbon flow toward precursors for industrial important metabolites.

Sterols are fundamental structural components of cellular membranes and are produced by most living systems. They are synthesized de-novo but can also be acquired from the diet. Cholesterol, a common form of sterol, is oxidized in the liver to form bile acids and is a critical substrate for steroid hormone biosynthesis. Plants produce a distinct set of sterols called phytosterols that are minimally absorbed, but that serve as markers of overall sterol absorption rates. The Cholesterol Metabolism Panel measures the total sterol content. The quantitative profile of cholesterol as well as intermediates in cholesterol synthesis and oxidation, phytosterols and metabolic products of cholesterol provides a comprehensive snapshot of sterol synthesis, absorption and excretion.

Fatty acids play many physiologically important roles in an organism. They are not only key metabolites of energy storage and production but also the basic building blocks of complex lipids that form cellular membranes. A variety of bioactive forms of fatty acid metabolites, known as lipid mediators, act as local hormones and are involved in many physiological systems and pathological processes (e. g. eicosanoids, lysophospholipids, resolvines, protectins, maresines). Dysregulation of fatty acid metabolism has been associated with many diseases.

Fatty acids play many physiologically important roles in an organism. They are not only key metabolites of energy storage and production but also the basic building blocks of complex lipids that form cellular membranes. A variety of bioactive forms of fatty acid metabolites, known as lipid mediators, act as local hormones and are involved in many physiological systems and pathological processes. Free fatty acids (FFA, non-esterified fatty acids, NEFA) are the non- bound fraction of the total fatty acid pool. The determination of FFAs in plasma (or serum) is of clinical relevance as the association between FFAs and many diseases is well-known (e. g. insulin resistance/type 2 diabetes, hypertension, cardiovascular disease).

Uremic toxicity is the buildup of toxic analytes that are not able to be adequately filtered by the kidneys due to kidney injury or disease. Indole metabolites of tryptophan, the tyrosine metabolite p-cresol sulfate and 4-ethylphenyl sulfate are a key group of gut microbiota-derived uremic compounds. Their formation is the result of a complex interaction between diet, gut microbiota and host. Increased production of these compounds by the gut microbiota and reduced clearance in kidney disease can lead to toxicity affecting nearly all systems in the body.

Malonylcarnitine is an indirect biomarker for malonyl-coenzyme A, a key intermediate of fatty acid biosynthesis.

Metabolon’s ICP-MS-based Metal Ions Panel provides precise measurements of biologically important metal ions in biological samples. In addition to the well-established problems of toxicity associated with several metals, the vital role these ions play in a variety of biological pathways whether by catalyzing enzymatic reactions or stabilizing protein structures is still becoming clear. Intimately intertwined with the proteome and metabolome, metal ions represent an intrinsic piece vital to the holistic understanding of biological phenomena ranging from development through normal functioning to disease. Without an understanding of the role of these metals, a complete understanding of biological processes is not possible. Metabolon’s Metal Ions Panel measures a variety of metals ions ranging from the macro level (ppm) including Na, K and Ca to the micro level (ppb) including Mo, Cu and Ni.

Polyamines are naturally abundant, low-molecular weight polycations that interact with negatively charged molecules such as DNA, RNA and proteins to modulate cellular functions such as gene transcription, protein translation, cell growth, membrane stability, and chromatic structure. Free, unbound polyamine levels within the cell are maintained within very narrow ranges (i.e., 7-10% of the total cellular polyamine content) and are strictly regulated since polyamine imbalance can have toxic effects on the cell. Changes in polyamine levels have been associated with aging and disease such as cancer.

Purines are heterocyclic aromatic organic compounds consisting of a pyrimidine ring fused to an imidazole ring. Xanthine, hypoxanthine and inosine are products of purine catabolism and are known reactive oxygen species (ROS) that contribute to oxidative stress. Purine metabolism imbalance leading to increases in catabolic by-products have been linked to endothelial dysfunction and vascular inflammation.

Daily monitoring glucose of levels is an essential part of managing diabetes. However, blood glucose testing usually involves finger pricks, an invasive procedure that is troublesome to some patients. Therefore, increasing efforts have been made to develop a non-invasive method by self-testing salivary glucose levels, which are two orders of magnitude lower than those in blood.

Short-chain fatty acids (SCFAs) are produced in the colon by the gut microbiota. They are the end products of anaerobic fermentation of dietary fibers and protein/peptides in the small intestine. Their formation is the result of a complex interaction between diet, gut microbiota and host. SCFAs influence the physiology of the colon serving as energy sources by host cells and the intestinal microbiota as well as participating in different host- signaling mechanisms.

Sebum is a complex mixture of lipids secreted by mature sebocytes onto the surface of skin. Sebum may have antimicrobial, photoprotection and vitamin delivery functions, and changes in the concentration and composition of sebum are related to acne and other skin disorders. Sebum is comprised of an unusual mix of lipid classes that is remarkably different in quantity and quality from lipids found in other organs. Major components are triglycerides, wax esters, squalene and free fatty acids. The fatty acid composition of the complex lipids and the free fatty acid fraction is unique to human skin. Large amounts of the unusual sapienic acid (16:1n10) as well as a variety of odd and branched chain fatty acids are present.

The stratum corneum possesses a diverse biochemical composition, including a variety of lipids which contribute to it’s important role in the barrier and water holding functions of the skin. When these functions are disrupted, it can lead to a variety of skin disorders such as psoriasis, dandruff and eczema. Utilizing metabolomics to measure the biochemical changes in the stratum corneum enables a deeper understanding of these and other skin coditions and offers improved monitoring of response to therapeutic intervensions.

Triacylglycerides (Triglycerides, TAGs) are esters of glycerol and three fatty acids. TAGs are a large class of lipids due to the variability of their fatty acid residues and their location on any of the three positions on the glycerol backbone. The main physiological function of TAGs in an organism is the storage of energy.

Trimethylamine (TMA) is a metabolite produced by certain gut bacteria from choline, betaine and carnitine found in red meat, eggs, fish and poultry. TMA is converted into TMAO in the liver and elevated plasma levels of TMAO have been linked to increased risk for major adverse cardiovascular events. Ongoing studies aim to determine if TMAO is a mediator of cardiovascular disease or a bystander in the disease process. Since specific gut bacteria play a central role in the production of TMAO, natural product therapeutics aimed at altering gut microbiota composition have gained interest.

Cholesterol is a fundamental structural component of animal cell membranes. Animals and humans synthesize primary sterol cholesterol de-novo but can also acquire it from dietary sources. Cholesterol is also the precursor for a wide variety of other physiologically important steroids such as bile acids and steroid hormones.

The kynurenine pathway is a metabolic pathway leading to the production of nicotinamide adenine dinucleotide (NAD+) from the enzymatic conversion of tryptophan. Immune activation leads to the formation of kynurenine with corresponding loss of tryptophan.

The kynurenine/tryptophan ratio has been used to reflect the activity of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) in cellular inflammatory response related to symptoms of depression, schizophrenia, and other neurological disease.

Vitamin D comprises of a group of secosteroids that play a significant role in calcium homeostasis and bone metabolism. Depending on the biosynthetic sterol precursor, either Vitamin D2 (from dietary ergosterol) or Vitamin D3 (from cholesterol) is formed in the skin in a photochemical reaction. Both are further hydroxylated to 25-hydroxy vitamin D2/D3 and 1,25-dihydroxy vitamin D2/D3, with the latter being the bioactive form. However, due to more favorable half-live in-vivo, the 25-hydroxy vitamin D2/D3 metabolites represent the best biomarkers for the assessment of vitamin D status.