Description
It provides you critical information on your patient’s:
-Glycolysis
-Fatty Acid Oxidation
-Ketone Metabolites
-Protein Metabolism
-Neurotransmitter Metabolism
-Detoxification Ability
-Citric Acid Cycle
-Bacterial Metabolism
Glycolysis
Pyruvate and Lactate are products of the glycolysis cycle (Figure 1) [1] and are key components of many metabolic processes. High values could indicate problems, either inborn or other causes, in multiple different pathways. There are at least five enzymes in this pathway, where a lack of activity could cause elevations of one or more of the markers in this section[1].
Lactate elevation can be caused by exercise [2].However, several toxins can inhibit mitochondrial ATP synthase. This inhibition can lead the body to produce more lactic acid [3]
Fatty Acid Oxidation, Ketone Metabolites, and Protein Metabolism
Succinyl-CoA is the major endpoint of this pathway, which is used in the TCA cycle (see figure 2). Elevations in these markers can be caused by ketogenic diets or exercise. Extreme elevations could be indicative of Maple Syrup urine disease or branched chain keto aciduria [8]. Branched chain amino acids (BCAA) function as metabolic regulators. However, higher levels have been associated with oxidative stress and mitochondrial dysfunction. These issues can lead to insulin resistance in some individuals [9]
Neurotransmitter Metabolism
Neurotransmitters are produced in multiple areas of the body from the central nervous system (CNS), the peripheral nervous system (PNS), and those produced in other parts of the body such as the renal system (see figure 3) . The correlation between the CNS neurotransmitter levels and excreted levels are still being researched, although several studies have suggested a link [10, 11]. However, the enzymes that are present in the CNS use the same cofactors. Elevations in precursors could indicate problems.The ratio between vanilmandelate and homovanillate could indicate low expression or activity of dopamine beta hydroxylase or other enzymes in the pathway [12].
Detoxification
Glutathione (GSH) is a non-protein tripeptide consisting of three amino acids: glutamate, cysteine, and glycine. (see figure 4) GSH is eventually decomposed into pyroglutamic acid. High amounts of pyroglutamic acid is an indicator of high oxidative stress [13]. Large amounts of pyroglutamic acid could indicate exposure to mycotoxins or other environmental pollutants. Elevated amounts could also indicate a glycine deficiency [14]. Extremely low amounts could indicate a deficiency in the production of glutathione which would cause an individual to become more sensitive to toxins [15].
Citric Acid Cycle
Now known as the TCA cycle (see figure 5) but is also called the Krebs’ cycle. This cycle is the predominant producer of ATP in most cells[4]. Dietary fruit consumption of orange, grapefruit, and lemon juices can increase urinary citrate levels [5]. Certain levels in this pathway can be increased by either LPS stimulation or toxins [6, 7].
Bacterial Metabolism
Dysbiosis is a common comorbidity for patients suffering from chronic illness. Identifying an overgrowth of pathogenic bacteria can assist in forming a treatment plan. (see figure 6) Markers such as Para-Hydroxyphenlacetate can indicate an overgrowth of Clostridium difficile [16].
