Fat metabolism question…

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  • #11150
    Tussock
    Participant

    Howdy you knowledgeable types:-

    I think I’ve got a rough idea of glucose metabolism: glucose undergoes glycolysis to produce NADH, pyruvate and/or lactate, then these are oxidised in the Krebs cycle, making products that then power the electron transfer chain, and the net result is gobs of ATP from glucose. More or less?

    But what I have no concept of is: how fat is metabolised. The thrust of the Uphill Athlete message seems to be that fat trained individuals who exercise close to but under their AeT build the most endurance fitness… by burning fat, which isn’t glycolysis. And that’s where I am completely baffled.

    I’m a 56 year old who has, in recent years, run a 2:31 marathon, climbed long alpine grade V routes, and had four cardiac stents put in. Yep, I have heart disease, and it seems you can still operate at a reasonable level with fairly blocked arteries. Scary stuff. I’ve been taking statins, and find that I cannot exercise close to AeT when taking statins as they produce severe delayed onset muscle soreness. I’ve quit taking the statins, but I’m experimenting to see what level of activity, and hence what metabolic pathway, is hampered by statin use… and while I have some information, I don’t know anything like enough about fat metabolism for energy production to make sense of any of this.

    As fat seems to be the fuel of choice for endurance, I would appreciate any information on how it is metabolised – party from curiosity, partly to see if I can resume taking statins.

    Thanks in advance!
    Bryan

Posted In: Nutrition

  • Keymaster
    Scott Johnston on #11154

    Bryan;

    Those are some very impressive accomplishments for and ‘old’ guy with a bum ticker! Good on you!

    Before I dig into your questions here’s a disclaimer: I have only a layman’s understanding of Biochemistry and Physiology. These processes, that I am about to so casually discuss are incredibly complex. Far, far too complex to give them anything like a full explanation in a couple of paragraphs. Entire text books are devoted to this topic and several years of rigorous study are involved to understand it.

    With that said: I can’t answer your question, especially as it relates to your medical condition with the stents/statins. You need to seek professional advice for that. I doubt you’ll find that level of understand and advice on any forum.

    You’re correct that NADH is a product of glycolysis along with its ATP. However a more important principle product of glycolysis as that process relates to aerobic metabolism is pyruvate which can be converted to acetyl CoA in the mitochondria. Acetyl CoA is the precursor for aerobic metabolism which takes place inside the mitochondrial matrix. Aerobic metabolism includes the Krebs Cycle and the electron transport chain (where most of the ATP is released). This is how glycolysis can lead to aerobic metabolism when there is adequate aerobic capacity in the muscle cell.

    Fat metabolism is known as lipolysis, of which a very crude and incomplete description is: Stored triglycerides are broken down and released into the blood as glycerin and free fatty acids. Those FFA are further converted, by way of particular enzymes, into Acetyl CoA. As in glycolysis, this acetyl CoA can then enter the mitochondrial matrix to undergo aerobic metabolism.

    Both these processes contribute to the overall energy needs of the muscle cell. Slow twitch muscle has a much higher mitochondrial density so is able to aerobically produce ATP in great quantity from either fat (using lipolysis) or carbs (using glycolysis). Fast twitch muscle, because it has less mitochondria, has to rely more on anaerobic glycolysis for its ATP supply.

    I hope this helps,
    Scott

    Participant
    Tussock on #11157

    Thanks Scott – that’s what I wanted to know. Is there a difference in ATP production between using fats and glucose, given the same amount of O2 for oxidation in the mitochondria?

    Much appreciated…
    Bryan

    Keymaster
    Scott Johnston on #11158

    If I understand your question correctly, YES. There is a vast difference in ATP output between anaerobic glycolysis at 2ATP vs the aerobic pathway in the mitochondria which is around 34-36 ATP depending on how you count.

    There is always lactate produced when glycolysis is the energy pathway there is never lactate produce when fat is the energy source. What is termed oxidative stress is much lower when fat is the fuel vs carbs.

    Scott

    Participant
    lionfish90 on #11164

    Most of our fat is stored as trigylcerides, which consist of 3 fatty acids (of varying length) bound to a glycerol backbone. We mobilize these, the fatty acids are released, and then the fatty acids are oxidized. They are highly reduced to begin with and go through many rounds of oxidation, in the end generating ATP because the acetyl-CoA which is produced from each round enters the TCA cycle from which ATP is generated. This process of “burning” fatty acids (which is oxidation of them to eventually form CO2 and water with the energy of the their bonds converted into the energy in ATP bonds, a form the body can use) is called “beta oxidation”. So if you want to learn more on the biochemistry of fat utilization, looking that up is a good place to start.

    If you want to know more about where the energy comes from, look up “redox reactions”. This Khan Academy page is a good summary:
    https://www.khanacademy.org/science/biology/cellular-respiration-and-fermentation/intro-to-cellular-respiration/a/intro-to-cellular-respiration-and-redox

    There, it says, “[E]lectrons are at a higher energy level when they are associated with less electronegative atoms (such as C or H) and at a lower energy level when they are associated with a more electronegative atom (such as O). So, in a reaction like the breakdown of glucose above, energy is released because the electrons are moving to a lower-energy, more “comfortable” state as they travel from glucose to oxygen.
    The energy that’s released as electrons move to a lower-energy state can be captured and used to do work. In cellular respiration, electrons from glucose move gradually through the electron transport chain towards oxygen, passing to lower and lower energy states and releasing energy at each step. The goal of cellular respiration is to capture this energy in the form of ATP.”

    That process is oxidative, meaning it requires oxygen, which eventually is going to accept those lower energy electrons. In other words, it is aerobic metabolism. It is also slower than anaerobic metabolism. When oxygen is limiting, we still need to generate ATP and do so using anaerobic processes, which are faster, in which carbohydrate is used in glycolysis (“sugar breakdown”) to generate ATP without using oxygen. The end product, pyruvate, can enter the TCA/aerobic cycle to form acetyl-CoA and ATP from that but only when oxygen is available. If not, the pyruvate is converted to lactate so that the anaerobic process can continue. (High levels of the products interfere with the enzymes trying to drive the reactions forward, so pyruvate is converted to lactate and the lactate is “handled” by shuttling to the blood and other cells. Eventually, high levels of products affect the system, and the athlete has to slow down because ATP production becomes limiting.)

    Thus, the mantra here (my current understanding of it, anyway) is to train in order to optimize your ability to mobilize fats and oxidize them during exercise. By training in that state where your body can use these processes, you stimulate adaptations to improve their use and efficiency. If you train in states where your body needs to mobilize other resources (such as high intensities requiring much glycolysis to supply the ATP needs), the body will adapt by increasing that anaerobic side of the house. The aerobic side gets relatively neglected because the stimulus saying, “We need more of this” is reduced compared to the stimulus for anaerobic adaptations. Generating all these enzyme systems is somewhat “expensive” to the body in maintenance terms, so the body has evolved to respond to stimuli with upregulation of those enzyme systems which are needed and downregulation of those which are not. Thus, the neglect is not just passive, in which you would keep whatever level of enzymes you previously had, but you will lose some of the existing capacity if you do not provide a stimulus to maintain it. What a bummer in our current environment where we are not energy-limited, but we are never that far from famine, so probably a good thing overall.

    A key insight to have, in my view, is the one about what “training harder” means. One wants to train each state “hard”. But when someone interprets “training harder” as that overall feeling of training “hard”, that person exits the aerobic state and starts training the anaerobic state hard. The aerobic state is actually getting a much lower training stimulus than is needed to make (or even maintain) the aerobic adaptations. So train hard, but know which system you are training. Preaching to the choir, but there you go.

    (I don’t know how statins interact in these processes, sorry to say!)

    Best,
    Rene’

    Participant
    lionfish90 on #11165

    PS–Re: statins, you might try here:
    http://journals.sagepub.com/doi/full/10.1177/2047487314550804
    Muscle- and skeletal-related side-effects of statins: tip of the iceberg?
    Johann Auer, Helmut Sinzinger, Barry Franklin, …
    First Published September 17, 2014 Research Article
    https://doi.org/10.1177/2047487314550804

    Abstract
    The clinical spectrum of muscle- and skeletal-related side-effects of statins includes varied myalgias and weakness, an asymptomatic increase in the concentration of creatine kinase and other biochemical parameters, myositis and rhabdomyolysis. Currently, there is no consensus on the definition of ‘statin myopathy’. Evidence suggests that deleterious effects may also be associated with the volume or dosage of structured exercise and/or the intensity of physical activity. Moreover, non-muscle adverse effects on the joints and tendons are often overlooked and underemphasized. The incidence of myopathy associated with statin treatment typically ranges between 1.5% and 10%. Few data are available regarding the prevalence of muscle- related symptoms associated with different statins and the distribution of affected muscles. Furthermore, discrepancies between clinical trials and daily practice may emanate, in part, because of inconsistent definitions or exclusion criteria.

    The pathophysiology of statin-related myopathy is incompletely understood. A dose-dependent and proapoptotic effect, direct effects on mitochondria, drug interactions and genetic factors, or combinations thereof, may be involved. Recently, a rare immune-mediated myopathy triggered by statin use has been described. With the increasing number of patients treated with statins and with more patients being prescribed high doses of potent statins to achieve low-density lipoprotein targets, muscle-related side-effects will become more prevalent. Currently, the only effective treatment is the discontinuation of statin use. Further research is needed to develop alternative LDL-lowering drugs when statins are not well tolerated and to establish additional effective strategies to manage lipids and lipoproteins.

    Keymaster
    Scott Johnston on #11166

    Well put Rene;

    In an even more succinct nutshell more digestible/useable for athletes and coaches is to consider Verkhoshansky’s description of this type of training as “anti-glycolytic”.

    By training extensively in the aerobic realm one increase the capacity to synthesize ATP from fat and lower the need for additional ATP to be contributed from glycolysis.

    Voila; More speed for longer with less fatigue. Isn’t that what we call endurance?

    Scott

    Participant
    Tussock on #11169

    Well, a BIG thanks to those who’ve posted – I’m learning heaps…

    There’s a strong suggestion that statins interfere with both the Citric Acid Cycle and the complexes that drive proton pumping – so, mitochondria are essentially damaged and out of the energy equation for those affected. It’s been my experience that virtually any level of exercise in any zone is severely hampered by statins, and recovery from what should be a gentle workout takes many days.

    It seems that for those affected, there is no option to exercise at any level while taking statins. I’ve stopped taking them for that reason.

    I’ve learned much from this site, and TFTNA. My old training method of run-up-a-big-hill-as-fast-as-posiible, repeat-as-often-as-possible and live of complex carbs while doing so, is being replaced by a smarter, and hopefully more effective, strategy. It is hard to back away from harder training, and the idea of no pain, no gain is difficult to let go, but I’m getting better. The information in this thread helps. Thanks again, everyone!

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