If you'll take a look at the top of the diagram, you'll note that for each NADH -> NAD+ and FADH2 -> FAD reduction reaction at the bottom, the hydrogen (simply a proton) is pumped out of the mitochondrial matrix\u00a0into the intermembrane space. \u00a0That hydrogen is shuttled through the inner membrane into the mitochondrial matrix where it\u00a0used in oxidative phosphorylation to make\u00a0ATP. \u00a0The hydrogen created from the reduction of NADH and FADH2 is not the only proton source in the body. \u00a0Protons from other sources are\u00a0also utilized by ATP Synthase in order to regenerate ATP. \u00a0But where else do we get hydrogen from and what does it have to do with acidosis?<\/p>\n Well, this is what happens in various parts of the cell: water hydrolyzes an ATP molecule, splitting it apart and creating energy in the process. \u00a0The resultant products are ADP (which will be phosphorylated in the mitochondrial matrix in the steps above) and an inorganic phosphate (to be used in a number of places, including in the phosphorylation of ADP as noted above) along with energy and an acidic H+ ion or proton. \u00a0When the cellular demand for ATP (to power muscle contractions) is met by the mitochondrial respiration, which is a fancy way of saying that would be that electron transport chain we saw above\u00a0is not at full capacity,\u00a0there's no net proton accumulation in the cell.<\/p>\n Basically, this\u00a0means that when you have sufficient mitochondrial efficiency (which could be considered\u00a0the equivalent of “fitness”) it's much harder to build up protons in your intermembranous space, which causes tissue\u00a0acidosis. \u00a0When you outstrip the capacity of the mitochondria to supply fresh ATP (generally due to lack of oxygen, insufficient transport protein capacity of the ETC or lack of enzyme availability from the ETC), anaerobic pathways kick in, hydrolyzing ATP for energy and those free protons build up and create a\u00a0“burning” acidosis.<\/p>\n It all works because as we hydrolyze\/break down ATP for energy, it's constantly being renewed by those protons that are pumped into the matrix of the mitochondria. \u00a0It's one huge recycling process.<\/p>\n Do you notice that there's nothing to do with lactate in there? \u00a0That's because lactate can actually REDUCE tissue acidosis. \u00a0Yeah, I said it…<\/p>\n It just so happens that increased lactic acid coincides with intermembranous acidosis and this fact makes it\u00a0a good marker of metabolic shift. \u00a0However, it doesn't mean that lactate is a bad thing; far from it. \u00a0It can actually be used by the body to create fuel in a process called gluconeogenesis, which happens back in the liver and involves yet another biochemical cycle, and your brain can actually run on lactate if need be<\/a>.<\/p>\n Furthermore, there's a contribution to muscle tissue acidity from K+ (potassium). \u00a0K+ is a positively charged ion that “leaks” from the cell cytoplasm during intense muscle contraction can contribute to the acidification of the intracellular fluids. \u00a0Interestingly, there is some evidence that lactate can actually increase the contractile force of muscles that are bathed in a hyperkalemic solution<\/a>. \u00a0Of course, these are in vitro studies, not in vivo, but the potential mechanism exists.<\/p>\n And yet another of the\u00a0important uses of lactate is to rebuild glycogen in our liver, which happens at rest or during low-intensity exercise.\u00a0That deserves its own discussion:<\/p>\n Since our bodies have evolved to be self-correcting, self-contained capsules that are able to power themselves via countless chemical reactions, there's got to be a way for the body to utilize the lactate that we produce. \u00a0It turns out, there is, and it sits right under your right ribs, and it's a hackable process that we can utilize to make even MORE energy for our cells. \u00a0In a nutshell, high-intensity interval training can help the body become efficient at shuttling lactic acid back into the liver, where the\u00a0Cori cycle<\/a>\u00a0processes it back into glucose.<\/p>\n Let's looks at the process:<\/p>\n The take home of this process is that high amounts of\u00a0\u03b2-oxidation along with decreased blood glucose and an increase in lactic acid production can stimulate this pathway and the enzymes within. \u00a0So when you include a variety of high-intensity work (or those isometric exercises I'll talk about in a minute) you increase lactic acid and start the Cori Cycle in action. \u00a0The biggest downside to this process is that it takes 6 ATP to complete, so it's only really able to happen at sub-threshold efforts. \u00a0In addition to Cori Cycle stimulation, you also deplete glycogen (and ATP) in muscle tissue, which activates the enzyme AMPK and stimulates mitochondrial proliferation.<\/p>\n Ok, so now we have a good, thorough understanding of what goes on in lactate production, metabolism and how it is actually beneficial to our body. \u00a0With that understanding, we can figure out a few ways to hack that system and gain performance out of this “byproduct.” \u00a0However, bear in mind that these interventions will not generally create a “night and day” difference in your performance. \u00a0What they will likely do is give you an extra 1\/2% or 1% performance gain at some of the higher intensities you may find within your races, fondos or group rides. \u00a0Make no mistake, even 1\/2% is worth a look at. Consider that people spend $3,000 for a pair of wheels that will shave 100 grams from their bike and maybe 2 seconds off their 10-12 minute climbing time.<\/p>\n Actually, in that light, these interventions might just be a bargain (and they are.)<\/p>\n If you're\u00a0not at all versed in chemistry, you may not be familiar with the concept of “rate limiting” steps. \u00a0Basically, as you can see above, reactions happen in a series of “steps” in our cells, and the speed at which the overall reaction occurs (in our example above, the speed at which lactate is converted to glucose) is limited by the slowest step in the chain. \u00a0That is the “rate limiter.” \u00a0In much of the body, rate limiters are put in place to maintain homeostasis in a normally functioning organism. \u00a0As athletes, we're not really normally functioning, but hopefully optimally functioning, so we need to “cheat” a little bit.<\/p>\n The most significant rate limiter in the Cori Cycle is the conversion of NAD (Nicotinamide Adenine Dinucleotide) into NADH (Nicotinamide Adenine Dinucleotide Hydrogenase). \u00a0It just so happens that research in the Journal of\u00a0the Federation of American Societies for Experimental Biology has shown that acute exposure to oxaloacetate enhances resistance to fatigue<\/a>. \u00a0It purportedly does this by increasing the conversion rate of NAD to NADH as well as providing an increase in the intermediary substrate in the lactic acid pathway.<\/p>\n So, if you want to use this little tidbit of knowledge to your advantage, you can take a 100mg or 200mg of supplemental oxaloacetate about a half hour before a high intensity workout to further stimulate these pathways. \u00a0You can also pop those oxaloacetate tabs before a strength training workout and really get the burn flowing if you want. \u00a0The biggest benefit of “hacking the burn” is the hormetic effect of increasing buffering enzymes and compounds in the body in response to high proton\/acid load.<\/p>\n You can get Isometrics are a secret weapon for endurance training, without doing hours of endurance training. \u00a0What what WHAT? \u00a0Yep, that's been found to be the case in a few studies, such as this one about blood pressure and mean arterial BP<\/a>.<\/p>\n Isometric exercise is a type of exercise that involves no gross movement of the joint, however still involves significant muscle contraction (imagine doing squats against a wall.) \u00a0This is in contrast to normal isotonic exercise which involves joint movement (which is what most of your normal riding is.) \u00a0If you've ever done wall squats, you'll be familiar with the agonizing burning sensation in your quads while you quiver and fight to stay upright against the wall. \u00a0That's lactic acid, and that's free performance right there, because the more you build up an acidic condition in the muscles (increased proton production) the more buffering enzymes you'll produce, which will help you tolerate proton build up during exercise.<\/p>\n As I briefly discussed above, an enzyme called AMPK stimulates your body to build new mitochondria. \u00a0This enzyme is stimulated when exercise is undertaken<\/a>, and there is research out there that demonstrates greater activation of AMPK with high intensity exercise<\/a>.\u00a0\u00a0It also happens to be increased when enhancing the function of the Cori cycle and with energy depletion in the cell (interestingly enough, carbohydrate and calorie restriction cause AMPK to be up-regulated as well. \u00a0More on that in a future post.) \u00a0Isometrics are heavily depleting on ATP stores, causing a buildup of AMP (Adenosine Mono Phosphate) and in turn activating AMPK. By performing a couple of sets per week of isometrics, you get a low impact training stimulus that builds lactate tolerance and stimulates AMPK to increase mitochondrial density. \u00a0You can tolerate more acidity in the muscles, you have more mitochondria to produce energy,\u00a0you can\u00a0process more fuel and create more ATP within the cell, and ultimately, you can store and preserve more ATP and glycogen in each cell. \u00a0That's a win in so many ways with very little time commitment or input.<\/p>\n So, now that you have the understanding of the lactic acid cycle and some of the ways to hack it for better performance, what are you going to do? \u00a0Are you going to add a few isometrics to your workout routine? \u00a0Are you going to hit the oxaloacetate before your strength workout<\/a>? \u00a0Are you going to head out and do some lactate tolerance intervals?<\/p>\n![\"Electron](\"https:\/\/tailwind-coaching.com\/wp-content\/uploads\/2014\/05\/ETC_overview.jpg\")
<\/a><\/p>\n![\"Lactic](\"https:\/\/tailwind-coaching.com\/wp-content\/uploads\/2014\/05\/Lactic_acid_fermentation-300x168.png\")
The reason lactic acid gets a bad rap is because as you move into anaerobic metabolism, you burn up more glucose, and burning up glucose requires NAD+ (Nicotinamide Adenine Dinucleotide), which is supplied by *SURPRISE* lactic acid production. \u00a0Take a look at the diagram to the left. \u00a0You'll notice that glucose is broken down into 2 pyruvate at the cost of 2 NAD+, leaving you with 2 NADH and 2 protons. \u00a0The next step of reducing pyruvate to lactate actually consumes those protons<\/a> that would otherwise be floating around in the cellular matrix. \u00a0So lactic acid production is something that actually mediates the proton concentration of the cellular matrix. If lactic acid indeed contributed to intermembranous acidosis, in the presence of lactic acid acidosis\u00a0would increase at an exponential rate (increased proton production = more easily overwhelmed mitochondria.)<\/p>\nThe Cori Cycle<\/h3>\n
![\"Biohacking](\"https:\/\/tailwind-coaching.com\/wp-content\/uploads\/2014\/05\/Cori-cycle-300x200.jpg\")
<\/a>The very same glucose that your body breaks down for energy.<\/p>\n\n
Keys to Biohacking Lactic Acid Beastliness<\/h2>\n
Oxaloacetate<\/h3>\n
Isometric Exercise<\/h3>\n
Wrapping\u00a0Up Biohacking Lactic Acid<\/h2>\n