Hompes Method Lesson 29 Organic Acids Part Three Health for the People Ltd not for reuse without expressed permission
Organic Acids - Review Fats, carbohydrates, and amino acids are converted into carboxylic acids before they flow on to the final conversion to carbon dioxide The organic acids that are formed as intermediates in this process are normally absent from urine or present at very low concentrations.
Organic Acids - Introduction When specific reactions are blocked due to the absence of sufficient enzyme or cofactor, the intermediates that precede the blocked step accumulate and spill into urine. Vitamin B 6 A-------- --------B-----------------C Urine
Energy Production Pathways Last Lesson THREE main stages: Stage I Oxidation of main fuels (cytoplasm). Stage II Citric Acid Cycle in mitochondria. Stage III Electron transport chains ad final ATP production. Last Lesson This Lesson
Stage I
Stage II It s important to understand that the CAC is going on inside mitochondria. Fats, proteins and sugars are converted into acetyl-coa, which then enters the CAC.
Stage I & Stage II - Discussion
Stage I & Stage II - Discussion
Stage III ET and OP Oxidative phosphorylation (or OXPHOS in short) is the metabolic pathway in which the mitochondria in cells use their structure, enzymes, and energy released by the oxidation of nutrients to reform ATP. Although the many forms of life on earth use a range of different nutrients, ATP is the molecule that supplies energy to metabolism.
Stage III ET and OP Almost all aerobic organisms carry out oxidative phosphorylation. This pathway is probably so pervasive because it is a highly efficient way of releasing energy, compared to alternative fermentation processes such as anaerobic glycolysis.
Stage III ET and OP During oxidative phosphorylation, electrons are transferred from electron donors to electron acceptors such as oxygen, in redox reactions. These redox reactions release energy, which is used to form ATP. In eukaryotes, these redox reactions are carried out by a series of protein complexes within the cell's intermembrane wall mitochondria, whereas, in prokaryotes, these proteins are located in the cells' intermembrane space.
Stage III ET and OP The electron transport chain carries both protons and electrons, passing electrons from donors to acceptors, and transporting protons across a membrane. These processes use both soluble and protein-bound transfer molecules.
Stage III ET and OP In mitochondria, electrons are transferred within the intermembrane space by the water-soluble electron transfer protein cytochrome c.this carries only electrons, and these are transferred by the reduction and oxidation of an iron atom that the protein holds within a heme group in its structure.
Stage III ET and OP Within the inner mitochondrial membrane, the lipidsoluble electron carrier coenzyme Q10 (Q) carries both electrons and protons by a redox cycle. [8] This small benzoquinone molecule is very hydrophobic, so it diffuses freely within the membrane. When Q accepts two electrons and two protons, it becomes reduced to the ubiquinol form (QH 2 ); when QH 2 releases two electrons and two protons, it becomes oxidized back to the ubiquinone (Q) form.
Stage III ET and OP As a result, if two enzymes are arranged so that Q is reduced on one side of the membrane and QH 2 oxidized on the other, ubiquinone will couple these reactions and shuttle protons across the membrane. Some bacterial electron transport chains use different quinones, such as menaquinone, in addition to ubiquinone.
Stage III ET and OP
Stage III ET and OP Hydroxymethylglutarate (HMG) is the metabolic precursor of both cholesterol and coenzyme Q10 (CoQ10). Low levels of HMG may reflect inadequate synthesis and possible deficiency of CoQ10.
Stage III ET and OP Drugs that are used to lower serum cholesterol by inhibiting the HMG-CoA reductase simultaneously inhibit the endogenous synthesis of CoQ10 and cause accumulation of the HMG intermediate in the pathway (we re talking about statins).
Stage III ET and OP Therefore, high levels of HMG reveal inhibition in the synthesis of CoQ10. CoQ10 is utilized in the mitochondrial oxidative phosphorylation pathway for ATP synthesis and is a potent antioxidant.
Stage III ET and OP It has been used extensively as a cardiovascular protective agent. Although it may seem paradoxical, cases where simultaneous low serum CoQ10 levels were found with low urinary HMG suggest that CoQ10 inadequacy may be associated with both low and high levels of HMG.
Stage III ET and OP The rationale for this association is that a block earlier in the pathway inhibits the formation of HMG producing low levels in urine, while a block subsequent to the formation of HMG produces high levels. A------>B------>HMG------>CoQ10/cholesterol
B-Vitamins Markers 15, 16, 17, 18 and 19 comprise a section in the Organix Profile called B-Complex Vitamin Status Markers. All the compounds in this category are metabolic intermediates in the degradation of amino acids. Note: why could amino acid degradation increase?
B-Vitamins Here is our core diagram for this section: Metametrix Organix Interpretive Guide
B-Vitamins The branched-chain amino acids are broken down to form α-ketoisovalerate, α-ketoisocaproate, and α- keto-β- methylvalerate. A dehydrogensase enzyme is needed for this step. Vitamins B 1, B 2, B 3, B 5, 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.
B-Vitamins Remember the previous two lessons: if pyruvate and α-ketoglutarate are also both elevated, then there may be a strong need for these specific nutrients since all of them utilize a dehydrogenase enzyme.
B-Vitamins B-vitamin insufficiency on its own may not be the answer: during the stress response, branched chain amino acids are broken down faster in order to produce glucose. The amino acids from gut tissue and muscles, etc. are sent to the liver and converted into glucose via gluconeogenesis. Could elevated keto-acids in markers 15, 16 and 17 be due to excess catabolism?
B-Vitamins Xanthurenate is marker 18 and is an indicator of B 6 deficiency. It s a by-product of tryptophan catabolism (hepatic). Your body needs vitamin B 6 (pyridoxine) to utilize amino acids derived from dietary protein. Inadequate vitamin B 6 is one factor that leads to increased concentrations of xanthurenate and kynurenate in urine.
B-Vitamins Xanthurenate interferes with insulin function and has even been proposed as a marker to both detect and track diabetes. Importantly, it is also an oxidative stressor it binds iron and forms a complex that increases DNA oxidative damage.
B-Vitamins There are other organic acid markers for assisting with B 6 assessment, namely kynurenate and quinolinate. We ll come onto those in the next session when we discuss neurotransmitter metabolism.
B-Vitamins Elevated levels of methylmalonate can indicate a B 12 insufficiency, and elevated levels B- hydroxyisovalerate can indicate a biotin insufficiency.
B-Vitamins β-hydroxyisovalerate is a biotin dependent catabolic product from isoleucine. An elevated β- hydroxyisovalerate indicates a need for biotin. β- Hydroxyisovalerate is a specific and sensitive metabolic marker for functional biotin deficiency.
B-Vitamins Methylmalonyl-CoA is produced in the multi-step process of breaking down valine into energy-yielding products. The intermediate is converted into succinic acid using a vitamin B 12 -dependent enzyme, methylmalonyl CoA mutase.
B-Vitamins A lack of vitamin B 12 impairs this conversion as well as the one in which methionine is recovered from homocysteine, leading to accumulation of both homocysteine and methylmalonate. If you see elevated methylmalonate, suspect elevated homocysteine (suspect H. pylori)
B-Vitamins Such biochemical impairment helps explain the fatigue resulting from vitamin B 12 deficiency and the rapid improvement of symptoms vitamin B 12 - deficient patients experience with administration of vitamin B 12. Vitamin B 12 deficiency has been demonstrated to be present in over 12% of the freeliving elderly population in the US and is especially common in the early stages of HIV infection.
B-Vitamins Why would B 12 be deficient? Chewing (or not!) R protein Stomach acid and intrinsic factor H. pylori, autoimmunity against parietal cells Increased energy demands Methylation demands Ileum damage (B 12 is mostly absorbed there)
B-Vitamins Formiminoglutamate (FIGLU) is a compound made from the amino acid histidine. Insufficiency of folic acid can lead to high urinary FIGLU. Folic acid is especially critical for prenatal and childhood development and in sufficient amounts is associated with lower risks of cardiovascular disease and cancer.
B-Vitamins Metametrix Organix Interpretive Guide
Stage III and B-Vitamins - Discussion It s very important that you don t just look at organic acid results and assume you can rectify the imbalances using supplements. The key is to look at the overall clinical picture and figure out why organic acid imbalances have developed.
Stage III and B-Vitamins - Discussion Why could CoQ10 levels decline? Statins Poor food choices Poor fat digestion (fat-soluble nutrient) Why would poor fat digestion develop? Chewing Pancreas Liver/gallbladder Intestinal inflammation
Stage III and B-Vitamins - Discussion Why could B-vitamins decline? Same reasons (except not fat-soluble) Poor diet, poor eating habits Gluten issues / inflamed intestines Low stomach acid / intrinsic factor (B 12 ) Excessive energy production (stress) Excessive use through detoxification pathways
Stage III and B-Vitamins - Discussion The B vitamin markers discussed in this lesson are markers of protein catabolism, which happens when the body perceives stress. Under the control of adrenaline/cortisol, the body will break down gut and lean tissue to provide amino acids from which to make glucose, in order to escape
Stage I & Stage II - Discussion Stress requires changes in metabolism to keep up with higher energy demands. It s not just life & death stress, or exercise that causes this. It s chronic stress, too. People can be running away from saber-toothed tigers 24/7! http://4.bp.blogspot.com/- SPOYBjpatIE/UGcSbHsHPgI/AAAAAAAAAGM/MDK1wyAGtqU/s1600/b aby+saber+tooth+tiger+picture.jpg
Stage I & Stage II - Discussion Don t just give supplements and expect miracles.
Thank You! Thanks a million for tuning in. I appreciate your time and I appreciate you choosing me as one of your teachers. In the next lesson we ll look at how the Organic Acids profiles can assist in ascertaining information on neurotransmitter balance, and we ll also review oxidative damage.