Part 5: Krebs cycle… that wonderful pathway you learned in biochemistry. Years later the Krebs cycle is back, and you are probably wondering what it means regarding your patient’s health. As you probably remember, the Krebs cycle is a series of mitochondrial chemical reactions necessary for cellular respiration in all living things. The substrates, enzymes, and products can all be a bit intimidating so here is what these Krebs cycle metabolites mean for your patient.
The Krebs cycle cannot function without the three macronutrient components which are essential to every diet: fats, carbohydrates, and proteins. It is therefore important to make sure patients have optimal dietary intake and nutritional status. Micronutrient cofactors are just as important for normal functioning, however, and in the 6 steps below, you will see how the Organix profile can help determine these micronutrient insufficiencies.
Adipate, suberate, and ethylmalonate are metabolites of impaired fatty acid metabolism; pyruvate and lactate are metabolites of carbohydrate breakdown; and proteins supply the body with amino acids which enter the Krebs cycle as keto acids. The Krebs cycle runs most effectively when it is fueled by the key nutrients and cofactors discussed below (their roles in the Krebs cycle are illustrated in the "Additional Resources" section at the end of this post):
- Low citrate, cis-aconitate, and isocitrate my indicate amino acid insufficiencies, where insufficient amino acids are entering these reactions elevations may indicate a need for arginine, lipoic acid, magnesium, or amino acid supplementation, because their elevations signal a possible issue in detoxification of ammonia via the urea cycle.
- Elevated α-ketoglutarate suggests a need for vitamins B1, B3, and B5. Low α-ketoglutarate suggests amino acid insufficiencies and the need for α-ketoglutarate.
- Elevated succinate, fumarate, and malate are indicative of coenzyme Q10 insufficiency.
- Elevated succinate suggests an insufficiency of coenzyme Q10, vitamin B2, and magnesium.
- Low succinate may also be indicative of low amino acids, specifically leucine and isoleucine.
- Low fumarate is indicative of low tyrosine and phenylalanine.
It is easy to see that insufficiencies of amino acids coming into the tissues (impaired amino acid metabolism) can result in low levels of Krebs cycle intermediates, as shown in numbers 1, 5, and 6 above. Sometimes it is even helpful for a patient to take free form amino acid powder the night before doing the test to ensure that pathways are stimulated, so that cofactor insufficiencies are demonstrated.
Depending on the degree of insufficiency and nutritional status, patients with elevated urinary organic acids metabolites may present with signs of weakness and fatigue. Nutrient insufficiencies may be a result of many factors including maldigestion/malabsorption, poor intake, food sensitivities, and chemical disruptors. The Organix Profile can aid in identifying these nutrient insufficiencies. The Organix Profile is also useful in identifying patterns of organic acid metabolite abnormalities to determine the degree of nutrient insufficiencies.
Additional Resources:
