Dr Yasko's replies on her forums
Abstract
Iron modulates the expression of the critical citric acid cycle enzyme aconitase via a translational mechanism involving iron regulatory proteins. Thus, the present study was undertaken to investigate the consequences of iron perturbation on citric acid cycle activity, oxidative phosphorylation and mitochondrial respiration in the human cell line K-562. In agreement with previous data iron increases the activity of mitochondrial aconitase while it is reduced upon addition of the iron chelator desferrioxamine (DFO). Interestingly, iron also positively affects three other citric acid cycle enzymes, namely citrate synthase, isocitric dehydrogenase, and succinate dehydrogenase, while DFO decreases the activity of these enzymes. Consequently, iron supplementation results in increased formation of reducing equivalents (NADH) by the citric acid cycle, and thus in increased mitochondrial oxygen consumption and ATP formation via oxidative phosphorylation as shown herein. This in turn leads to downregulation of glucose utilization. In contrast, all these metabolic pathways are reduced upon iron depletion, and thus glycolysis and lactate formation are significantly increased in order to compensate for the decrease in ATP production via oxidative phosphorylation in the presence of DFO. Our results point to a complex interaction between iron homeostasis, oxygen supply and cellular energy metabolism in human cells.
MMA converts to succinate in the presence of B12. When succinate combines with glycine it generates porphyrins. Thus increased levels of MMA and/or succinate can ultimately lead to increases in biochemical porphyrin products after reaction with excess glycine. If high levels of porphyrins are seen on a porphrin test it is important to check glycine levels to determine if high glycine along with high citric acid intermediates (ie succinate) are the actual source of the high porphyrins. Keep in mind that certain nutritional supports will also increase glycine levels which in turn may influence the levels of biochemical products such as hippuric and prophryrins. High levels of support with trimethylglycine (TMG), or the direct supplementation with glycine may increase both glycine and sarcosine, which can in turn increase porphyrin and hippuric acid levels. TMG is also called betaine, which is contained in the digestive support Betaine HCl.
Research articles illustrate a relationship between B12 and ATP which seems to present a catch 22. ATP, the fuel generated by your body to drive its biochemical reactions, is created by your Krebs energy cycle. The Krebs cycle needs B12 in order to function optimally. If your Krebs cycle is not functioning optimally, ATP production is reduced. Yet, ATP is needed to transport B12 into your cells. However, lithium also plays a role in B12 transport, so lithium levels should be checked and supported as needed. MitoForce or ATP, NADH, Vitamin E succinate, and Malic Acid also play a role in B12 transport and may be supplemented as needed.
Overall mitochondrial/Krebs support can include: pantothenic and riboflavin along with carnitine to help the flow at 12:00 into the cycle. Lactoferrin, GSH and curcumin depending on genetics and other test values to move from 1:00 to 2:00. NADH, riboflavin, niacinamide, ATP, benfotiamine to get you around to 7:00 to succinate. Vitamin E succinate, various forms of B12 (hydroxy, methyl ,adenosyl), CoQ10 and vitamin K to get beyond the succinate/MMA issues and then the direct use of carnitine fumarate if needed as well as malic acid. Remember that malic is the point just before oxalate, it is also helpful for aluminum which can inhibit at earlier steps in the cycle.
High levels of sulfur in your system can have a negative impact on the regeneration of ATP and NADH. This may be a particular issue for those who are SUOX + – or CBS ++.
