Alpha-Keto-Beta-Methylvalerate

Urine
Optimal Result: 0 - 1.29 ug/mg creatinine.

Alpha-Keto-Beta-Methylvalerate is a B-Complex Vitamin Marker. Vitamins are compounds that your body needs to be healthy. Vitamins are “essential” for proper function, which means that they are not made inside your body and must be consumed in the diet. The B-complex vitamins are necessary for many enzymes in your body to function properly. Your body uses enzymes to extract energy from food, to build new tissue, to remove toxins, and to maintain the immune system. The branched-chain amino acids are broken down to form α-ketoisovalerateα-ketoisocaproate, and α-keto-β-methylvalerate.

A dehydrogensase enzyme is needed for this step. Vitamins B1, B2, B3, B5, and lipoic acid are needed for this dehydrogenase to function properly. If these nutrients are insufficient, the keto acids may build up in the urine.

References:

http://ctdbase.org/detail.go?type=chem&acc=C016211

https://www.gdx.net/uk/core-uk/interpretive-guides-uk/Organix-IG.pdf

http://www.oxfordreference.com/view/10.1093/oi/authority.20110803095405411

What does it mean if your Alpha-Keto-Beta-Methylvalerate result is too low?

Low levels of alpha-keto-beta-methylvalerate may occur if there are low levels of precursors (isoleucine), if there are nutritional enzyme inhibitions, or if a low-activity enzyme variant is inherited. The enzyme that converts isoleucine into alpha-keto-beta-methylvalerate is vitamin B6 dependent, and this step in the BCAA breakdown pathway is shared by all of the BCAAs. Either a nutritional deficiency or an inherited metabolic disorder may decrease the levels of all the BCAA-derived analytes (alpha-ketoisovalerate, alpha-ketoisocaproate, alpha-keto-beta-methylvalerate, beta-hydroxyisovalerate).

1. Consider supporting synthesis with vitamin B6. If B6 is deficient then alpha-ketoglutarate, fumarate, kynurenate, para- hydroxyphenyllactate, alpha-hydroxybutyrate, para-hydroxyphenylacetate and neurotransmitters may also be lower than expected.

2. BCAA supplementation may have beneficial effects in patients with muscle wasting, which can occur after acute critical illness or with chronic conditions such as cirrhosis, kidney failure, etc.

What does it mean if your Alpha-Keto-Beta-Methylvalerate result is too high?

High levels of alpha-keto-beta-methylvalerate may occur when there are nutritional enzyme inhibitions of the breakdown pathways, inherited low-activity enzymes are present, if there are high levels of precursors (protein, amino acids, isoleucine), or if there are higher levels of its downstream products. Higher levels of circulating BCAAs have been associated with obesity, metabolic syndrome, cardiovascular and hypertension risks. Higher circulating levels of leucine and isoleucine have been associated with cardiovascular risk. The risk appears to be associated with low-activity enzymes in the breakdown pathway. Higher levels may inhibit the malate-aspartate shuttle and electron transport chain (ETC) complex I and III. ETC inhibition decreases ATP levels and cellular energy. Inborn errors of metabolism, such as maple syrup urine disease, increase levels of alpha keto acids which act as neurotoxins in the central nervous system.

1. Consider supporting the breakdown of alpha-keto-beta-methylvalerate with vitamins B1, B2, B3, B6, and r-lipoic acid.

2. Consider supporting the malate-aspartate shuttle with vitamins B3, B6, and calcium.

3. Consider supporting ETC complex III with vitamins B2, B3, B5, B12, E, CoQ10, L-carnitine, melatonin, selenium, taurine, and zinc if indicated. Dicarboxylic acids (cis-aconitate, isocitrate, succinate, malate, suberate, and adipate) may also be elevated if there are certain ETC defects.

4. Urinary orotate levels may increase if liver disorders, urea cycle disorders or other inherited metabolic disorders are present. Adipate and suberate may also increase if liver disorders are present. Inborn errors of metabolism may increase the levels of all the keto-acids (alpha-ketoisovalerate, alpha-ketoisocaproate, alpha-keto-beta-methylvalerate, beta-hydroxyisovalerate).

5. Evaluate risk of metabolic syndrome or type II diabetes if indicated.

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