Lactic Acid

Optimal Result: 3.7 - 39.2 ug/mg CR.

Lactic Acid and Pyruvic Acid are byproducts of glycolysis. Carbohydrates, which contain glucose, are broken down through glycolysis to form pyruvate and two ATP molecules. Pyruvate can also be generated through the catabolism of various amino acids, including alanine, serine, cysteine, glycine, tryptophan and threonine. Magnesium is an important cofactor for a number of glycolytic enzymes necessary to produce pyruvate. Optimally, pyruvic acid is oxidized to form Acetyl-CoA to be used aerobically via the Citric Acid Cycle to produce energy. In an anaerobic state, lactic acid is formed instead.

References:

- ieczenik SR, Neustadt J. Mitochondrial dysfunction and molecular pathways of disease. Exp Mol Pathol. 2007;83(1):84-92.

- Depeint F, Bruce WR, Shangari N, Mehta R, O'Brien PJ. Mitochondrial function and toxicity: role of the B vitamin family on mitochondrial energy metabolism. Chemico-biol Interact. 2006;163(1-2):94-112.

- Gray LR, Tompkins SC, Taylor EB. Regulation of pyruvate metabolism and human disease. Cell Mol Life Sci. 2014;71(14):2577-2604.

- Garfinkel L, Garfinkel D. Magnesium regulation of the glycolytic pathway and the enzymes involved. Magnesium. 1985;4(2-3):60- 72.

- Mayes PA, Bender DA. Glycolysis and the oxidation of pyruvate. Harper’s illustrated biochemistry (Eds RK Murray, DK Granner, PA Mayes, VW Rodwell) pp. 2003:136-144.

- Ravindran S, Radke GA, Guest JR, Roche TE. Lipoyl domainbased mechanism for the integrated feedback control of the pyruvate dehydrogenase complex by enhancement of pyruvate dehydrogenase kinase activity. J Biol Chem. 1996;271(2):653-662.

- Shipman K. Clinical biochemistry: Metabolic and clinical aspects (3rd edn). In: SAGE Publications Sage UK; 2015.

- Tirmenstein MA, Mathias PI, Snawder JE, Wey HE, Toraason M. Antimony-induced alterations in thiol homeostasis and adenine nucleotide status in cultured cardiac myocytes. Toxicology. 1997;119(3):203-211.

- Chapatwala KD, Rajanna B, Desaiah D. Cadmium induced changes in gluconeogenic enzymes in rat kidney and liver. Drug Chem Toxicol. 1980;3(4):407-420.

- Schlecht I, Gronwald W, Behrens G, et al. Visceral adipose tissue but not subcutaneous adipose tissue is associated with urine and serum metabolites. PloS one. 2017;12(4):e0175133.

- Friedrich N, Skaaby T, Pietzner M, et al. Identification of urine metabolites associated with 5-year changes in biomarkers of glucose homoeostasis. Diab Metab. 2017.

- Mostafa H, Amin AM, Teh CH, Murugaiyah V, Arif NH, Ibrahim B. Metabolic phenotyping of urine for discriminating alcoholdependent from social drinkers and alcohol-naive subjects. Drug Alc Depend. 2016;169:80-84.

- Hira HS, Shukla A, Kaur A, Kapoor S. Serum uric acid and lactate levels among patients with obstructive sleep apnea syndrome: which is a better marker of hypoxemia? Ann Saudi Med. 2012;32(1):37-42.

- Nikolaidis S, Kosmidis I, Sougioultzis M, Kabasakalis A, Mougios V. Diurnal variation and reliability of the urine lactate concentration after maximal exercise. Chronobiol Int. 2018;35(1):24-34.

- Tamaki N, Ikeda T, Funatsuka A. Zinc as activating cation for muscle glycolysis. J Nutr Sci Vitaminol. 1983;29(6):655-662.

- Ikeda T, Kimura K, Morioka S, Tamaki N. Inhibitory effects of Zn2+ on muscle glycolysis and their reversal by histidine. J Nutr Sci Vitaminol. 1980;26(4):357-366.

- Kaplan RS, Mayor JA, Blackwell R, Maughon RH, Wilson GL. The effect of insulin supplementation on diabetes-induced alterations in the extractable levels of functional mitochondrial anion transport proteins. Arch Biochem Biophys. 1991;287(2):305-311.

What does it mean if your Lactic Acid result is too low?

Low levels of pyruvic acid might imply low carbohydrate intake, lack of magnesium cofactors for glycolytic enzymes, or lack of insulin.

What does it mean if your Lactic Acid result is too high?

An elevated pyruvic acid would reflect an inability to form Acetyl-CoA to feed the Citric Acid Cycle. Pyruvate uses the pyruvate dehydrogenase complex to form Acetyl-CoA. A different enzyme, pyruvate carboxylase, is responsible for the conversion of pyruvate into oxaloacetate. Nutrient cofactors, such as vitamin-B1, B2, B3, B7, magnesium, and lipoate are needed to support the pyruvate dehydrogenase and pyruvate carboxylase enzymes.

Insufficiency in any of these nutrients can raise levels of pyruvic acid. In vitro studies have shown there are some toxins that can also affect these enzymes, such as antimony, mercury, and cadmium.

Pyruvate elevations can also be seen with a high intake of carbohydrates, as well as rare genetic forms of pyruvate dehydrogenase deficiency.

Any anerobic or low oxygen state, including pulmonary disease, anemia, sleep apnea, among others can lead to elevations of lactic acid.

Elevations of urinary lactic acid can also be the result of strenuous exercise, insulin resistance, dysglycemia, and alcohol dependence.

Zinc is an essential component in the enzymes which regulate glycolysis, such as lactate dehydrogenase (LDH). LDH converts lactate back to pyruvate in the liver via the Cori cycle. Elevations may be seen with a functional need for zinc.

Clinical Associations: Pyruvate metabolism abnormalities play important roles in cancer, heart failure, and neurodegeneration.

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