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What Is Gluconeogenesis?

what-is-gluconeogenesis
So, your friend who follows the ketogenic diet with you told you that you should cut back on the amount of protein that you’re eating, because it can kick you out of the state of ketosis thanks to gluconeogenesis. You probably were a little concerned, because you already let go of your love of bread, and now you’re worried about having to say goodbye to steak. Don’t worry. You don’t have to say goodbye to your steak or any other protein for that matter! <i>Gluconeogenesis</i> a process that permits your kidneys and liver to create glucose from sources that don’t contain any carbohydrates<sup>1</sup>. No matter what your diet looks like or if you’re in a state of ketosis, gluconeogenesis is always happening in your body, although the rate of gluconeogenesis does change depending upon the metabolic state of your body. Today, we’re going to tell you everything you need to know about how gluconeogenesis is actually keeping you alive! Plus, we’ll talk about what gluconeogenesis does, how different metabolic rates affect gluconeogenesis, why your body needs gluconeogenesis, and how gluconeogenesis affects your ketogenic diet. <div class="text-left my-5"> <img class="img-fluid w-md-75 image-center" src="https://s3.us-east-2.amazonaws.com/wm-wmade-static-media/media/public/Assets/images/dna-in-blue-image.jpg" alt="dna in blue image"> </div> Let’s dive right in! <h4><p style="color: rgba(20, 117, 135, 1)">What Is the Purpose of Gluconeogenesis?</p></h4> Good news: the purpose of gluconeogenesis isn’t to throw you out of a state of ketosis. Broken down, the word gluconeogenesis, <i>gluco</i> (glucose), <i>neo</i> (new), <i>genesis</i> (creation), literally means <i>the creation of glucose</i>. However, gluconeogenesis only develops glucose from noncarbohydrates<sup>18</sup>! As you may already understand, there are some organs in your body that depend upon carbohydrates to function properly. So, when you start cutting back on your carbohydrate intake, your internal organs stop relying on the glucose they get from carbs to work efficiently<sup>1</sup>. But not all of your internal organs can work efficiently without glucose. The reason your body converts proteins and odd chain fatty acids to glucose is because some of your body’s internal organs can only use glucose for an energy source<sup>2</sup>. Your brain, the <i>kidney medulla</i> (the innermost part of your kidneys), and testes all depend on gluconeogenesis to produce glucose as their source of energy when you’re not consuming carbohydrates<sup>3</sup>. While simple sugars and simple carbohydrates aren’t considered health-boosting elements to consume for your body, your internal organs do depend on glucose to be able to function properly. That’s why when you eat protein, some of the protein that you consume is converted into glucose to be used for energy through gluconeogenesis. In other words, gluconeogenesis is absolutely necessary to keep you alive when you aren’t eating any carbohydrates! If you’re worried about if Gluconeogenesis affects your ketogenic diet, skip to ‘Does My Body Still Need Gluconeogensis If I’m In Ketosis’! <h4><p style="color: rgba(20, 117, 135, 1)">What Are the Steps of Gluconeogenesis?</p></h4> Just so the terminology doesn’t get confusing, let’s take a second to talk about <i>glycolysis</i> versus <i>gluconeogenesis</i>. But just as a warning, this entire process is very dense in science terminology, so we’ve just broken down the basics of the entire process. Glycolysis is the term used to describe the process of changing glucose into energy<sup>6</sup>. Your body has two different types of responses: one process that builds products and the other process that breaks down products. In the creation of products, energy is needed to be able to create. When products are being broken down, energy is created. At the opposite end of the spectrum, gluconeogenesis requires extra energy to be put into a reaction in order for gluconeogenesis to occur<sup>4</sup>. It’s also important that you understand two of your body’s metabolic conditions: <ul> <li>Your body’s normal metabolic condition, where you’re eating a high-carb diet</li> <li>Low carb or zero carb intake or when you’re fasting</li> </ul> <h5 style="font-size: 1.5rem;">High Carb Conditions</h5> While you’re consuming a high-carb diet, your body relies on three types of nutrient for energy: <ol> <li>Fat</li> <li>Protein</li> <li>Carbohydrates</li> </ol> After you’ve eaten, your body works on digesting food for energy. The carbohydrates that you’ve eaten are broken down into glucose, any of the protein that you’ve eaten turns into amino acids, and fat into fatty acids. All of these nutrients are absorbed and are either burned for energy right away or saved to be used for energy at a later date. When it comes to carbohydrates, your body stores carbs in your muscles and in your liver in a form called glycogen. <h5 style="font-size: 1.5rem;">Glycolysis</h5> In order to get energy from the food that you eat, your body has a metabolic pathway called Glycolysis. For your body to be able to complete glycolysis, the pyruvate kinase enzymes, hexokinase enzymes, and the phosphofructokinase enzymes are all needed. Glycolysis is the process your body goes through to deconstruct a carbohydrate<sup>5</sup>. A singular molecule of glucose has six carbons. During the glycolysis process, your body breaks down the glucose into two individual three-carbon molecules of pyruvate<sup>6</sup>. After that, your body takes pyruvate to the mitochondria, where your body breaks off one molecule for the three-carbon molecule, which created acetyl coenzyme A<sup>6</sup>. Woah, that was a lot of science! But hold on, we’re not done yet. <h5 style="font-size: 1.5rem;">Carb-Fasting Conditions</h5> So, what does your body do when you eat a diet that’s high in protein? The first thing that your body does is use up all of your glycogen stores that your body has been storing away in your muscles and in your liver. Oh no- now your body is out of glycogen! What happens next? Your body loves carbs, because glucose is easier for your body to use for fuel. But, if you’re not eating carbohydrates, your body actually makes glucose from sources that don’t contain any glucose. This process is called <i>gluconeogenesis</i>! <h5 style="font-size: 1.5rem;">Gluconeogenesis</h5> Your body can actually make glucose from glycerol, oxaloacetate, lactate, and amino acids<sup>5</sup>. When you’re feeding your body a high-carb diet, oxaloacetate is always available to be paired up with acetyl coenzyme A to be able to form citrate. During this time, Oxaloacetate can typically be refilled from pyruvate<sup>6</sup>. Now since you’ve started eating a low carb diet and you’ve actually used up all of your stored glucose energy, you’ve also exhausted your ability to make pyruvate from oxaloacetate and oxaloacetate from pyruvate! Your body can’t use the same three enzymes that it depended on for glycolysis, so it developed three other enzymes to be able to use for gluconeogenesis. The pyruvate carboxylase enzymes, PEP carboxykinase enzymes, and the malate dehydrogenase enzymes are what are used for gluconeogenesis<sup>4</sup>. You can find pyruvate carboxylase in the mitochondria of your cell, as pyruvate carboxylase is what helps to convert pyruvate into oxaloacetate<sup>4</sup>. However, because oxaloacetate can’t pass through the membrane of the mitochondria, your body has to convert malate into malate dehydrogenase. After malate has been transformed into malate dehydrogenase, malate takes a journey into your cell’s cytoplasm! Once malate dehydrogenase has made it to the cytoplasm safely, it’s converted back into oxaloacetate by being paired up with another malate dehydrogenase<sup>4</sup>. Wow- that was a lot of work! In case you want a better understanding of how your body produces glucose from protein, we have a complete scientific breakdown of all of the steps your body goes through during gluconeogenesis<sup>4</sup>. <div class="text-left my-5"> <img class="img-fluid w-md-75 image-center" src="https://s3.us-east-2.amazonaws.com/wm-wmade-static-media/media/public/Assets/images/steps-of-gluconeogenesis-infographic.jpg" alt="steps of gluconeogenesis infographic"> </div> Gluconeogenesis shares a very similar process to glycolysis, only the entire process is in reverse. While the entire process seems complex, gluconeogenesis is absolutely necessary for your body to be able to function. <div class="text-left my-5"> <img class="img-fluid w-md-75 image-center" src="https://s3.us-east-2.amazonaws.com/wm-wmade-static-media/media/public/Assets/images/blood-cells-in-body.jpg" alt="blood cells in body"> </div> <h4><p style="color: rgba(20, 117, 135, 1)">When Does Gluconeogenesis Start Happening?</p></h4> No matter if you’re following a strict ketogenic diet or if you’re eating a high-carb diet, your body is <i>always</i> using gluconeogenesis. However, the rate of gluconeogenesis significantly increases when your consumption of carbohydrates is limited. But if it’s always happening, what are the precursors of gluconeogenesis? Depending on your metabolic state, gluconeogenesis behaves differently. Here’s how<sup>9</sup>: <h5 style="font-size: 1.5rem;">During Intermittent Fasting</h5> A popular form of <a target="_blank" href="https://www.warriormade.com/content/diet/how-to-use-intermittent-fasting-to-accelerate-your/"><strong>fasting to help accelerate weight loss</strong></a> that’s commonly paired with the <a target="_blank" href="https://www.warriormade.com/content/diet/intermittent-fasting-and-keto-should-you-do-them/"><strong>ketogenic diet</strong></a>, intermittent fasting actually helps to boost the rate of gluconeogenesis<sup>10</sup>. While you’re participating in an intermittent fast, your body produces 50 percent of its glucose from gluconeogenesis while the other 50 percent comes from glycogenosis<sup>9</sup>. <h5 style="font-size: 1.5rem;">During a Fast</h5> If you’re participating in an extended fast that isn’t intermittent fasting, your blood sugar levels may start dropping, but your body is going to be in a constant state of gluconeogenesis. So, if you’re participating in an extended fast in hopes of getting into a state of ketosis faster, understand this: when your glycogen stores run out, your body will become completely dependent upon gluconeogenesis<sup>11</sup>. <h5 style="font-size: 1.5rem;">While You’re Following the Ketogenic Diet</h5> As we talked about above, once your glycogen stores run dry, gluconeogenesis is going to completely take over. However, when you follow the ketogenic diet, your body goes through two different metabolic stages when you’re first starting out<sup>13</sup>: <ul> <li>A period of fat adaption</li> <li>The state of true ketosis</li> </ul> <h5 style="font-size: 1.5rem;">Gluconeogenesis While Adapting Fat</h5> For the first couple of days while you’re following the ketogenic diet, your body’s stores of glycogen will start to become depleted, resulting in the decline of your glucose levels. However, during these first couple of days, your body isn’t producing enough ketones to run off of, so it keeps taking its energy from your glucose stores. Research states that after an average of five weeks without carbs, your body switches from running on glycogenosis to gluconeogenesis<sup>11</sup>. <h5 style="font-size: 1.5rem;">Gluconeogenesis After Fat Adaption</h5> Yay, your body is now adapted to fat and you’re running off of ketones! Studies have shown that after your body has become adapted to fat and is producing ketones, the rate of gluconeogenesis is nearly two times higher than it was when your body was learning to become fat adapted<sup>13</sup>. <h5 style="font-size: 1.5rem;">After You Eat</h5> While gluconeogenesis plays a very small part in the production of glucose after you consume a high-carb meal, gluconeogenesis is constantly happening<sup>9</sup>. So, even if you’re following the ketogenic diet, gluconeogenesis is always happening. However, the rate of gluconeogenesis will vary depending upon the metabolic state that your body is in! Basically, your Gluconeogensis is <i>always</i> happening in your body. But, your rate of Gluconeogenesis may change depending on your metabolic state! <h4><p style="color: rgba(20, 117, 135, 1)">Does My Body Still Need Gluconeogenesis if I’m in Ketosis?</p></h4> Yes, absolutely! Even though the rate of gluconeogenesis is increased while your body is fat adapted, your body is still going to run on ketones without any difficulty. The reason is because while you’re in ketosis, the glucose that is produced from gluconeogenesis isn’t being used as a dependent fuel source for your body. Instead, your body uses the glucose to: <ul> <li>Supply energy to the tissues and organs in your body that can’t use ketones</li> <li>Prevent hypoglycemia</li> <li>Restock your body’s glycogen stores <sup>14</sup></li> </ul> Any extra glucose that your body produces from gluconeogenesis is stored as glycogen, which is what your body uses to prevent hypoglycemia in case your blood sugar levels drop too low<sup>15</sup>. However, not many people know that glucose is an incredibly important part of feeding your body energy while you’re working out. While you’re exercising, your body is going through anaerobic glycolysis, which is when your body produces lactate. After your body starts to produce lactate in your muscles, the lactate moves into your liver where it’s changed into pyruvate using the lactate dehydrogenase enzyme. Once the lactate dehydrogenase has been converted into pyruvate, your body then has the ability to create glucose<sup>5</sup>. During a state of ketosis, your body’s gluconeogenesis process goes towards storing up extra glucose as glycogen<sup>14</sup>. If you were to follow a high-carb diet, your body would store fat and run off of glucose. On the ketogenic diet, your body runs off of ketones and stores glucose as glycogen! So, while you’re in ketosis, your body is only using gluconeogenesis to stock up on glycogen stores to prevent hypoglycemia and to help your muscles recover after you exercise<sup>14</sup>. <div class="text-left my-5"> <img class="img-fluid w-md-75 image-center" src="https://s3.us-east-2.amazonaws.com/wm-wmade-static-media/media/public/Assets/images/raw-meat-on-table-with-rosemary.jpg" alt="raw meat on table with rosemary"> </div> <h4><p style="color: rgba(20, 117, 135, 1)">Will Eating Too Much Protein Kick Me Out of Ketosis?</p></h4> No, eating too much protein won’t kick you out of ketosis. Your body produces ketones because in the long run, they’re a more effective fuel source than glucose. If you’re following the ketogenic diet, eating too much protein will not kick you out of ketosis. Why? Gluconeogenesis is always happening in your body, even if you’re in a state of ketosis. Even if you decided that you didn’t want to eat any protein at all, gluconeogenesis is still going to happen. However, instead of using the protein that you’re eating to convert to glucose, your body will start using your lean muscle mass for glucose<sup>17</sup>. Plus, ketosis actually suppresses your body’s glucose production! Your body finds it so much easier to run off of ketones for energy than it does using glucose for energy. In other words, your body literally fights off the state of gluconeogenesis taking over by releasing ketones<sup>9</sup>. <div class="text-left my-5"> <img class="img-fluid w-md-75 image-center" src="https://s3.us-east-2.amazonaws.com/wm-wmade-static-media/media/public/Assets/images/woman-posing-on-beach.jpg" alt="woman posing on beach"> </div> <h4><p style="color: rgba(20, 117, 135, 1)">Not Eating Enough Protein Is Dangerous</p></h4> There are a lot of inexperienced keto dieters out there that will tell you that eating too much protein will kick you out of ketosis―don’t listen to them. Not eating enough protein is actually very unhealthy and can cause negative side effects if you go for a long enough period without adequate protein<sup>19</sup>. Not eating enough protein on any diet can cause: <ul> <li>Decreased workout performance <sup>9</sup></li> <li>Decreased muscle mass <sup>19</sup></li> <li>Weakened immune system <sup>9</sup></li> <li>Increased risk of infection <sup>19</sup></li> <li>Slowed healing time <sup>19</sup></li> </ul> To reap the <a target="_blank" href="https://www.warriormade.com/content/diet/ketosis-and-brain-function/"><strong>benefits that the ketogenic diet</strong></a> can bring to your body and to keep your health optimal, it’s incredibly important to make sure you’re eating enough protein. <h4><p style="color: rgba(20, 117, 135, 1)">Gluconeogenesis Is Your Friend</p></h4> Your body needs gluconeogenesis to survive as it provides your tissues and organs with enough energy to function normally. Not only that, but the glucose that gluconeogenesis creates prevents your body from going into hypoglycemia, rebuilds your glycogen stores, and helps your muscles repair themselves after a workout. The extra protein you’re looking to eat during the day to have more energy or to feel fuller will not kick you out of ketosis. Even if your extra protein serving takes you out of your macros for the day, you’re still not going to be kicked out of ketosis. To learn more about the ketogenic diet and how you can create a healthier lifestyle for yourself, check out our <a target="_blank" href="https://www.warriormade.com/content/diet/"><strong>nutrition section</strong></a>. Not only do we have more information about the keto diet, we also have complete guides to help answer all of your keto diet questions plus beginner tips for starting the ketogenic diet and tons of tasty keto recipes! <h5 style="font-size: 1.5rem; margin-top:30px;">References:</h5> 1. <a target="_blank" href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/gluconeogenesis">Gluconeogenesis</a> 2. <a target="_blank" href="https://biology.stackexchange.com/questions/31135/what-is-the-purpose-of-gluconeogenesis">What Is The Purpose of Gluconeogenesis?</a> 3. <a target="_blank" href="https://www.ncbi.nlm.nih.gov/books/NBK22436/">Each Organ Has A Unique Metabolic Profile</a> 4. <a target="_blank" href="https://study.com/academy/lesson/gluconeogenesis-definition-steps-pathway.html">Gluconeogenesis: Definition, Steps, and Pathway</a> 5. <a target="_blank" href="https://sciencing.com/difference-between-glycolysis-gluconeogenesis-8711255.html">The Difference Between Glycolysis and Gluconeogenesis</a> 6. <a target="_blank" href="https://www.khanacademy.org/science/biology/cellular-respiration-and-fermentation/glycolysis/a/glycolysis">Glycolysis: Cellular Respiration</a> 7. <a target="_blank" href="https://www.khanacademy.org/science/biology/cellular-respiration-and-fermentation/pyruvate-oxidation-and-the-citric-acid-cycle/a/pyruvate-oxidation">Pyruvate Oxidation</a> 8. <a target="_blank" href="https://www.sciencedirect.com/topics/neuroscience/pyruvate-carboxylase">Pyruvate Carboxylase</a> 9. <a target="_blank" href="https://perfectketo.com/gluconeogenesis/">Gluconeogenesis: What It Is</a> 10. <a target="_blank" href="https://medium.com/lifeomic/time-restricted-feeding-how-and-when-you-break-your-fast-matters-f241d40950f3">Time-Restricted Feeding</a> 11. <a target="_blank" href="https://www.ncbi.nlm.nih.gov/pubmed/18561209"> Regulation of Hepatic Glucose Production</a> 12. <a target="_blank" href="https://www.healthline.com/nutrition/ketogenic-diet-101">The Ketogenic Diet: A Detailed Beginner’s Guide</a> 13. <a target="_blank" href="https://academic.oup.com/jcem/article/85/5/1963/2660569">The Effects of Carbohydrate Variation</a> 14. <a target="_blank" href="https://www.todaysdietitian.com/newarchives/110413p18.shtml">Post Exercise Recovery</a> 15. <a target="_blank" href="https://www.niddk.nih.gov/health-information/diabetes/overview/preventing-problems/low-blood-glucose-hypoglycemia">Low Blood Glucose</a> 16. <a target="_blank" href="https://www.ruled.me/what-is-gluconeogenesis/">What Is Gluconeogenesis?</a> 17. <a target="_blank" href="https://www.marksdailyapple.com/how-much-protein-on-keto/">Protein Intake While Keto: Why It Matters</a> 18. <a target="_blank" href="https://medical-dictionary.thefreedictionary.com/gluconeogenesis">Gluconeogenesis</a> 19. <a target="_blank" href="https://www.verywellfit.com/what-are-the-effects-of-protein-deficiency-4160404">The Effects of Protein Deficiency</a>

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