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Mastering Nutrition

Hi, I'm Chris Masterjohn and I have a PhD in Nutritional Sciences. I am an entrepreneur in all things fitness, health, and nutrition. In this show I combine my scientific expertise with my out-of-the-box thinking to translate complex science into new, practical ideas that you can use to help yourself on your journey to vibrant health. This show will allow you to master the science of nutrition and apply it to your own life like a pro.
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Oct 10, 2017

In conditions of glucose deprivation, such as fasting or carbohydrate restriction, ketogenesis serves to reduce our needs for glucose. This reduces the need to engage in the energetically wasteful process of gluconeogenesis, which would otherwise be extremely taxing on our skeletal muscle if dietary protein were inadequate. Ketogenesis mainly occurs in the liver. The biochemical event that leads to ketogenesis is an accumulation of acetyl CoA that cannot enter the citric acid cycle because it exceeds the supply of oxaloacetate. The set of physiological conditions that provoke this biochemical event are as follows: free fatty acids from adipose tissue reach the liver, providing the energy needed for gluconeogenesis as well as a large excess of acetyl CoA. Oxaloacetate, with the help of the energy provided by free fatty acids, leaves the citric acid cycle for gluconeogenesis. These events increase the ratio of acetyl CoA to oxaloacetate, which leads to the accumulation of acetyl CoA that cannot enter the citric acid cycle and therefore enter the ketogenic pathway. This pathway results in the production of acetoacetate, a ketoacid. Acetoacetate can then be reduced to beta-hydroxybutyrate, a hydroxyacid, in a manner analogous to the reduction of pyruvate, a ketoacid, to lactate, a hydroxyacid. Acetoacetate is an unstable beta-ketoacid just like oxalosuccinate (covered in lesson 6) and can also spontaneously decarboxylate to form acetone, a simple ketone that is extremely volatile and can evaporate through the lungs, causing ketone breath. This lesson covers the basic mechanisms of ketogenesis and sets the ground for the forthcoming lesson on the benefits and drawbacks of ketogenesis in various contexts.

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Oct 9, 2017

The last lesson covered how insulin, glucagon, and allosteric regulators from within the liver ensure that the liver only engages in gluconeogenesis when it can and when it needs to. This lesson focuses on an additional layer of regulation: cortisol. Cortisol is the principal glucocorticoid in humans. Glucocorticoids are steroid hormones produced by the adrenal cortex that increase blood glucose. Cortisol has multiple actions on the liver, muscle, adipose, and pancreas that all converge on making glucose more available to the brain. Among them, it increases movement of fatty acids from adipose to the liver, which provide the energy for gluconeogenesis, and the movement of amino acids from skeletal muscle to the liver, which provide the building blocks for gluconeogenesis. Cortisol serves both to antagonize insulin, thereby acutely increasing gluconeogenesis, and to increase the synthesis of gluconeogenic enzymes, which amplifies all other pro-gluconeogenic signaling and increases the total capacity for gluconeogenesis. In fact, even the day-to-day regulation of gluconeogenesis by glucagon is strongly dependent on normal healthy levels of cortisol in the background. Since gluconeogenesis is an extremely expensive investment with a negative return, it makes sense that the body would regulate it as a stress response, and thus place it under control by cortisol. This raises the question of whether carbohydrate restriction increases cortisol. Several studies are reviewed in this lesson that indicate that 1) there may be an extreme level of carbohydrate restriction that always increases cortisol, and 2) carbohydrate restriction definitely increases cortisol in some people. It may be the case that other stressors in a person’s “stress bucket” determine whether and how strongly the person reacts to carbohydrate restriction with elevated cortisol.

For the full episode, go to chrismasterjohnphd.com/mwm/2/31

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Oct 8, 2017

Since gluconeogenesis is extremely expensive, it has to be tightly regulated so that it only occurs when both of two conditions are met: 1) the liver has enough energy to invest a portion into synthesizing glucose, and 2) the rest of the body is in need of that glucose.

Since the liver is the metabolic hub of the body that also plays a major role in anabolic synthesis and nitrogen disposal, it also regulates glycolysis and gluconeogenesis according to whether amino acids are available to supply energy in place of glucose and whether there is sufficient citrate and associated energy for biosynthesis. This lesson covers how insulin, glucagon, alanine, citrate, fructose 2-6-bisphosphate, ATP, ADP, and AMP regulate the flux between glycolysis and gluconeogenesis.

For the full episode, go to chrismasterjohnphd.com/mwm/2/30

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Oct 7, 2017

Gluconeogenesis is extremely expensive. Three steps of glycolysis are so energetically favorable that they are irreversible. Getting around them requires four gluconeogenesis-specific enzymes and the investment of a much larger amount of energy. Overall, six ATP worth of energy are invested to yield glucose, a molecule that only yields 2 ATP when broken down in glycolysis. This lesson covers the details of the reactions as well as the rationale for investing so much energy. One of the most pervasive themes in biology is the drive to conserve energy. That we will spend this much energy synthesizing glucose is a testament to how essential it is to our life and well being.

For the full episode, go to chrismasterjohnphd.com/mwm/2/29

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Oct 6, 2017

Insulin is commonly seen as a response to blood glucose whose primary role is to keep blood glucose within a narrow range. This view of insulin fails to account for its many roles outside of energy metabolism that govern long-term investments in health. The biochemistry and physiology of insulin secretion suggest, rather, that insulin is a gauge of short-term energy status and energetic versatility. Since glucose can only be stored in small amounts and since it is the most versatile of the macronutrients in its ability to support specialized pathways of energy metabolism, it makes sense that it would be wired to the pancreas as the primary signal of short-term energy status and energetic versatility. In this lesson, we review the unique uses of glucose and the mechanisms of insulin signaling to synthesize them into a more nuanced view of the role of insulin than is typically presented.

For the full episode, go to chrismasterjohnphd.com/mwm/2/28

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Oct 5, 2017

The pentose phosphate pathway provides a deep look into a stunning array of essential roles for glucose. In it, glucose becomes the source of NADPH, used for antioxidant defense, detoxification, recycling of nutrients like vitamin K and folate, and the anabolic synthesis of fatty acids, cholesterol, neurotransmitters, and nucleotides. At the same time, glucose also becomes the source of 5-carbon sugars, used structurally in DNA, RNA, and energy carriers like ATP, coenzyme A, NADH, NADPH, and FADH2. DNA is needed for growth, reproduction, and cellular repair; RNA is needed to translate genetic information from DNA into all of the structures in our bodies; the energy carriers constitute the very infrastructure of the entire system of energy metabolism. This lesson covers the details of the pentose phosphate pathway, how it operates in multiple modes according to the relative needs of the cell for ATP, NADPH, and 5-carbon sugars, the role of glucose 6-phosphate dehydrogenase deficiency and thiamin deficiency in its dysfunction, and what it means for the importance of glucose to human health.

For the full episode, go to chrismasterjohnphd.com/mwm/2/27

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Oct 4, 2017
In August of this year, 25-year-old bodybuilding mom Meegan Hefford was found unconscious in her apartment, brought to the hospital where she was declared brain-dead, and died soon after. The cause? "Too much protein before competition," according to the New York Post. She had recently doubled her gym routine, started dieting, and begun slamming protein shakes in preparation for an upcoming bodybuilding competition. No one knew she had a rare genetic disorder that would make the breakdown of protein acutely toxic for her until after her death.
 
Does this tragic case carry lessons for the rest of us without rare genetic disorders? In this episode, I make the answer a definitive YES.
 
Protein is essential to life and health, but its metabolic byproduct, ammonia, is toxic. Humans dispose of excess nitrogen largely as urea, a nontoxic metabolite of ammonia that can be safely excreted in the urine. Rare genetic defects like Hefford's interfere directly with the production of urea. Other genetic defects that interfere with the use of certain fuels, especially fatty acids and branched-chain amino acids, can indirectly impair the synthesis of urea during metabolic crisis. Impairments of urea synthesis lead to the accumulation of ammonia, with devastating neurological consequences.
 
Null genes manifest in infancy and are best studied. Partial genetic deficiencies, like Hefford's are often asymptomatic through adulthood until dietary changes (protein supplementation, carbohydrate restriction, fasting) or metabolic demands (intense exercise, illness) force a greater rate of protein catabolism.
 
There is at least one genetic polymorphism in a urea cycle gene that is COMMON and associated with disease: the A allele of rs5963409 in the OTC gene is present in up to 25-30% of some populations. It impairs ammonia disposal and arginine synthesis and it increases the risk of hypertension and Alzheimer's disease.
 
Does it impair protein tolerance? It hasn't been directly studied, but it is reasonable to believe that people with this polymorphism may not tolerate protein as well as others, and that arginine supplementation could help. 
 
We need to stop dismissing inborn errors of metabolism as too rare to be relevant and we need to start connecting the dots and learning the lessons they carry for everyone.
 
This episode is brought to you by Paleovalley. I use their beef sticks as a convenient yet nutritious snack. They are made from 100% grass-fed beef and preserved through traditional fermentation. The fermentation makes them more digestible and gives them a fresher mouthfeel and texture compared to most other meat snacks I’ve tried, which tend to be too dry for me to fully enjoy. They also have a grass-fed organ complex that contains a blend of liver, heart, kidney, and brain, all stuffed into gel caps for those who can’t bring themselves to eat these incredibly nutritious meats with a fork. Head to paleovalley.com and enter the promo code masterjohn at checkout for 30% off your order. This is a huge savings available for only a limited time. You can get 30% off everything on the site, ordering as much as you want, but only for the duration of the next three podcast episodes. Check it out now to make sure you get your discount!
 

This episode is brought to you by US Wellness Meats. I use their liverwurst as a convenient way to make a sustainable habit of eating a diversity of organ meats. They also have a milder braunschweiger and an even milder head cheese that gives you similar benefits, as well as a wide array of other meat products, all from animals raised on pasture. Head to grasslandbeef.com and enter promo code “Chris” at checkout to get a 15% discount on any order that is at least 7 pounds and is at least $75 after applying the discount but under 40 pounds (it can be 39.99 lbs, but not 40). You can use this discount code not once, but twice!

Oct 4, 2017

Although insulin promotes storage of fat in adipose tissue, this occurs in the context of multiple layers of regulation where energy balance is the final determinant of how much fat we store. In a caloric deficit, the low energy status of muscle and heart will lead them to take up fat rather than adipose tissue, even in the presence of insulin. Insulin combined with low energy status will promote the uptake of glucose in skeletal muscle over adipose tissue and will promote the oxidation of glucose rather than its incorporation into fat. Some advocates of the carbohydrate hypothesis of obesity have argued that glucose is needed to form the glycerol backbone of triglycerides within adipose tissue. Although glucose can serve this role, it isn’t necessary because adipose glyceroneogenesis and hepatic gluconeogenesis can both provide the needed glycerol phosphate. Further, low energy status promotes the use of glycerol as fuel and high energy status is needed to promote the formation of glycerol from glucose. Finally, fatty acids are needed to store fat in adipose tissue and they overwhelmingly come from dietary fat in almost any circumstance. Insulin can only promote de novo lipogenesis, the synthesis of fatty acids from other precursors such as carbohydrate, in the context of excess energy, and this pathway is minor in conditions of caloric deficit, caloric balance, or moderate caloric excess. Thus, although insulin does promote storage of fat in adipose tissue, it doesn’t directly affect energy balance, and energy balance is the determinant of how much fat you store overall.

For the full episode, go to chrismasterjohnphd.com/mwm/2/26

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Oct 3, 2017

Insulin prevents fat-burning in part by locking fat in adipose tissue and in part by shutting down transport of fatty acids into the mitochondrion inside cells. By downregulating lipoprotein lipase (LPL) at heart and skeletal muscle and upregulating it at adipose tissue, insulin shifts dietary fat away from heart and muscle and toward adipose tissue. By downregulating hormone-sensitive lipase in adipose tissue, it prevents the release of free fatty acids from adipose tissue into the blood. At the cellular level, insulin leads to the phosphorylation and deactivation of AMPK. Since AMPK inhibits acetyl CoA carboxylase, insulin-mediated deactivation of AMPK leads to activation of acetyl CoA carboxylase and the conversion of acetyl CoA to malonyl CoA. Malonyl CoA inhibits carnitine palmitoyl transferase-1 (CPT-1) and thus blocks the transport of fatty acids into the mitochondrion. Nevertheless, all of these steps are also regulated at the most fundamental level by energy status, as covered in lesson 22. Further, insulin stimulates the burning of carbohydrate for energy, as covered in lesson 24. So, is insulin’s blockade of fat-burning sufficient to cause net fat storage, or does this critically depend on energy balance? This question will be answered in the next lesson.

For the full episode, go to chrismasterjohnphd.com/mwm/2/25


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Oct 2, 2017

Most people interested in health and nutrition know that insulin clears glucose from the blood into cells, but it is much less widely appreciated that insulin also makes you burn that glucose for energy. Insulin stimulates the translocation of GLUT4 to the membrane of skeletal muscle, heart, and adipose cells, and activates hexokinase 2. GLUT 4 increases the rate of glucose transport across the cell membrane and hexokinase 2 locks the glucose into the cell, making sure that glucose travels inward rather than outward. Insulin stimulates glycogen synthase, causing you to store glucose as glycogen, but it also stimulates pyruvate dehydrogenase, causing you to burn pyruvate for energy. The key determinant of which one of these you do is the energy status of the cell. Glucose 6-phosphate is needed to activate glycogen synthase, and it only accumulates if high energy status is inhibiting phosphofructokinase. If low energy status is stimulating phosphofructokinase, the net effect of insulin is to irreversibly commit glucose to glycolysis, and then to stimulate the conversion of pyruvate to acetyl CoA, which then enters the citric acid cycle to allow the full combustion of the carbons and maximal synthesis of ATP. Thus, if you need the energy, the net effect of insulin is to make you burn glucose to get that energy.

For the full episode, go to chrismasterjohnphd.com/mwm/2/24


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Oct 1, 2017

Insulin secretion. Remarkably, we know from dietary studies that we get the most insulin from eating carbohydrate, yet we know from molecular and cellular studies that insulin secretion is primarily triggered by the ratio of ATP to ADP inside the pancreatic beta-cell. The former implies that insulin is a response to glucose, while the latter implies that insulin is a response to total energy availability. What can explain this discrepancy? In this lesson, we explore the possibility that it is the anatomy and physiology that drive the dietary effect of carbohydrate rather than the biochemistry. Carbs are wired to get soaked up by the pancreas when blood sugar rises above the normal fasting level once the liver has taken its share to replete hepatic glycogen, whereas fats are wired to go primarily to the heart and muscle when those organs need energy and to go primarily to adipose tissue otherwise. The combination of circulatory routes and the relative expression of glucose transporters and lipoprotein lipase by different tissues likely directs fat to the pancreatic beta-cell as a source of ATP only during extreme hyperglycemia or when it exceeds adipose storage capacity due to obesity, insulin resistance, or very high-fat meals. The pancreatic beta-cell does have a diversity of complicated and often controversial secondary biochemical mechanisms that “amplify” the insulin-triggering effect of ATP, and carbs are more versatile at supporting these mechanism than fat. These likely make a contribution to the dietary effect, but they strike me as unlikely to be the primary driver of the dietary effect. Thus, insulin is a response mainly to carbohydrate availability but also to total energy availability, and this driven mainly by the anatomy and physiology but also by the biochemistry. Seeing insulin as a response to cellular energy status will eventually help us broaden our view of insulin as a key governor of what to do with that energy that goes far, far beyond regulating blood glucose levels.

For the full episode, go to chrismasterjohnphd.com/mwm/2/23

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Sep 30, 2017

This lesson covers the regulation of beta-oxidation. The primary regulation of beta-oxidation occurs at the mitochondrial membrane, where fatty acids are transported into the mitochondrion. Acetyl CoA carboxylase governs both the formation of fatty acids from non-carbohydrate precursors and the transport of fatty acids into the mitochondrion. Its product, malonyl CoA, is a substrate for fatty acid synthesis in the cytosol but a regulator of fatty acid transport in the mitochondrion. Thus, there are two isoforms of acetyl CoA carboxylase that are regulated similarly. The cytosolic isoform plays a direct role in fatty acid synthesis and the mitochondrial isoform regulates beta-oxidation. This ensures that the two processes are regulated reciprocally, so that one is shut down to the extent the other is activated, thereby preventing wasteful futile cycling. The primary regulator of acetyl CoA carboxylase activity is, as you might expect by this point, energy status. When a cell needs more energy, it lets fatty acids into the mitochondrion. When it has too much, it shuts down fat-burning.

For the full episode, go to chrismasterjohnphd.com/mwm/2/22

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Sep 29, 2017

This lesson covers the regulation of glycolysis. The principle regulation occurs at phosphofructokinase, which guards the gate to the first irreversible, committed step to burn glucose for energy. What governs it? Energy. If you need more ATP, you burn more glucose; if you don’t, you don’t. If the cell has glucose beyond its needs for energy, it uses it for the pentose phosphate pathway, which allows the production of 5-carbon sugars and antioxidant defense if needed, or stores it as glycogen if there is room. If not, glucose-6-phosphate accumulates and shuts down hexokinase. This, together with low AMPK levels, causes glucose to get left in the blood. The other key regulated step of glycolysis is pyruvate kinase, where the primary purpose of regulation is to prevent futile cycling between steps of glycolysis and gluconeogenesis. On the whole, glycolysis and glucose uptake are regulated primarily by energy status and secondarily by glucose-specific decisions about the need for glycogen or for the pentose phosphate pathway. Since we mostly use glucose for energy under most circumstances, the key regulation of the pathway is the regulation of phosphofructokinase by energy status. This means glucose uptake is largely driven by energy status, and our decisions about preventing hyperglycemia should center on total energy balance.

For the full episode, go to chrismasterjohnphd.com/mwm/2/21

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Sep 27, 2017

In this lesson, we examine the entire glycolytic pathway. We use as our theme the transfer of oxygen from phosphate to newly generated water. This explains why the standard stoichiometry of glycolysis found in textbooks show it generating two water molecules, and ties the information together with the analogous principles from substrate-level phosphorylation in the citric acid cycle and the relative differences in water consumption and carbon dioxide generation between fat and carbohydrate. As with our discussion of the citric acid cycle, we also reveal why the standard stoichiometry of glycolysis is misleading and why, when we account for atoms rather than molecules, we find glycolysis to be net water-neutral.

For the full episode, go to chrismasterjohnphd.com/mwm/2/19

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Sep 27, 2017

In this lesson, we examine the beta-oxidation in its simplest form: the breakdown of a long-chain, saturated fatty acid. We see once again the principle that the oxygen content of a molecule determines how much water its metabolism consumes and how much carbon dioxide its metabolism releases. In beta-oxidation, we consume one water per round and release no carbon dioxide. This reflects the fact that fatty acids are not hydrates of carbons like sugars are, which is where the name carbohydrate comes from.

 

For the full episode, go to chrismasterjohnphd.com/mwm/2/20

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Sep 26, 2017

Can fat fuel intensity in a competitive athlete? This lesson takes a critical look at the commonly cited evidence in favor of a neutral or beneficial effect of low-carbohydrate or ketogenic diets on sports performance, as well as key pieces of conflicting evidence. Bottom line? Fat can fuel duration, but probably can never fuel your peak intensity, just as the physiology would predict.

For the full episode, go to chrismasterjohnphd.com/mwm/2/18

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Sep 25, 2017

Can athletes fat-adapt their workouts? This lesson lays down the principles of exercise biochemistry and physiology needed to understand the importance of the three energy systems supporting energy metabolism in skeletal muscle: the phosphagen system (ATP and creatine), anaerobic glycolysis (dependent on carbs), and oxidative phosphorylation (dependent on carbs, fat, or protein). We discuss why maximal intensity always depends on carbs if the intensity and duration are sufficient to deplete phosphocreatine concentrations, and clarify the window of time and intensity that can be fat-adapted. This sets the foundation for the next lesson, which looks at the evidence of how carbohydrate restriction and ketogenic diets impact sports performance.

For the full episode, go to chrismasterjohnphd.com/mwm/2/17

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Sep 18, 2017

“Anaplerosis” means “to fill up” and refers to substrates and reactions that fill up a metabolic pathway as its own substrates leak out for other purposes. The citric acid cycle is a central example of this because its intermediates are often used to synthesize other components the cell needs. On a mixed diet where carbohydrate provides much of the energy, pyruvate serves as the main anaplerotic substrate. During carbohydrate restriction, protein takes over. Fat is the least anaplerotic of the macronutrients because the main product of fatty acid metabolism, acetyl CoA, is not directly anaplerotic. There are several very minor pathways that allow some anaplerosis from fat, but they are unlikely to eclipse the need for protein to support this purpose during carbohydrate restriction. Thus, carbs and protein are the two primary sources of anaplerosis. This means carbs can spare the need for protein, and that protein requirements rise on a carb-restricted diet.

For the full lesson, go to chrismasterjohnphd.com/mwm/2/16

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Sep 12, 2017

One of the advantages of carbohydrate over fat is the ability to support the production of lactate. This is so important that carbohydrate is physiologically essential to red blood cells and certain brain cells known as astrocytes. For the same reason, it plays an important role in supporting the energy requirements of the lens and cornea, kidney medulla, and testes, and supports the quick boosts of peak energy needed during stressful situations that include high-intensity exercise. The biochemical role of lactate is to rescue NAD+ during times when NAD+ becomes limiting for glycolysis and glycolysis becomes a meaningful source of ATP. Through the Cori cycle, lactate can extract energy from the liver’s supply of ATP and deliver it to other tissues such as skeletal muscle in the form of glucose. This lesson fleshes out the physiological and biochemical roles of lactate and serves as a foundation for the next lesson, which explores the role of carbohydrate in supporting sports performance.

Watch the full lesson at chrismasterjohnphd.com/mwm/2/17

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Sep 10, 2017

Did you realize that thiamin deficiency can be caused by your environment? In the old days, beriberi was associated with the consumption of white rice. Nowadays, refined foods are an unlikely cause of thiamin deficiency because they are fortified. We associate deficiency syndromes such as Wernicke’s encephalopathy and Korsakoff’s psychosis primarily with chronic alcoholism. Yet there are regional outbreaks of thiamin deficiency among wildlife attributed to poorly characterized thiamin antagonists in the environment. Thiamin-destroying amoebas can pollute water, thiamin-destroying bacteria have been isolated from human feces, and thiamin-destroying fungi have also been identified. Could toxic indoor molds and systemic infections play a role as well?

Thiamin deficiency is overwhelmingly neurological in nature and hurts the metabolism of carbohydrate much more than fat. Indeed, preliminary evidence suggests thiamin supplementation can help mitigate glucose intolerance. Ketogenic diets are the diets that maximally spare thiamin and are best characterized as treatments for neurological disorders. Anecdotally, ketogenic diet-responsive neurological problems sometimes arise as a result of infection. Could ketogenic diets be treating problems with thiamin or thiamin-dependent enzymes? One must exercise caution here: fat contains little thiamin, and ketogenic diets can actually cause thiamin deficiency if they don’t contain added B vitamins. The relationships between thiamin, glucose metabolism, and neurological health are remarkable and desperately need our attention.

For the full lesson, go to chrismasterjohnphd.com/mwm/2/14

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Sep 9, 2017

The pyruvate dehydrogenase complex catalyzes the one decarboxylation step that carbohydrate undergoes to generate acetyl CoA, which accounts for the one carbon dioxide molecule produced in carbohydrate metabolism that is not produced during the metabolism of fat. It also accounts for why burning carbs requires twice as much thiamin as fat. In fact, the pyruvate dehydrogenase complex is remarkably analogous to the alpha-ketoglutarate dehydrogenase complex, sharing all the same cofactors and catalyzing virtually the same reactions. In this lesson, we look at why this has to be true and how it works. This provides the foundation for our deeply practical look at thiamin in the next lesson.

chrismasterjohnphd.com/mwm/2/13

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Sep 7, 2017

Since carbs are richer in oxygen than fat, they consume less water in their metabolism and release more carbon dioxide. Carbon dioxide puts stress on the lungs and its generation should be restricted in the case of lung injury to allow healing. This calls for a low-carbohydrate, high-fat diet. On the other hand, carbon dioxide is needed to support the action of vitamin K and biotin, and to promote delivery of oxygen to tissues during exercise.

In our first glimpse into glycolysis and beta-oxidation, we find that understanding the basic chemical makeup of these molecules is deeply relevant to how we would manipulate the diet in many contexts of health and disease.

For the full lesson, go to chrismasterjohnphd.com/mwm/2/12

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Sep 6, 2017

Now we take it clinical: how do we use what we’ve learned so far to interpret the section of a urinary organic acids test that reports the citric acid cycle metabolites?

We begin by looking at the underlying chemistry to explain the curious absence of oxaloacetate on these tests. We conclude by mastering the ability to spot three unique patterns: energy overload, oxidative stress, and thiamin deficiency.

For the full lesson go to chrismasterjohnphd.com/mwm/2/11

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Sep 5, 2017

This lesson looks at the fundamental principle that atomic oxygen is the limiting factor for the release of carbon dioxide in metabolism, and when we don’t have enough we take it from water. This will become very relevant when we cover fats versus carbohydrates, because they consume different amounts of water and release different amounts of carbon dioxide for this very reason. That, in turn, relates to a number of health endpoints such as the functions of vitamin K and biotin, delivery of oxygen to tissues, and the stress placed on the lungs during breathing.

Here, we look at the principle in the citric acid cycle. In doing so, we see that, while textbooks only point to two water molecules consumed, a third water molecule is irreversibly consumed to donate oxygen to the cycle via phosphate.

For the full lesson, go to chrismasterjohnphd.com/mwm/2/7

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Sep 4, 2017

This lesson addresses the curious case of why CoA makes a brief cameo in the citric acid cycle during the formation of succinyl CoA only to leave again in the next step. We dig into the chemistry underlying the high-energy thioester bond that CoA forms with acyl groups, which explains more broadly one of the key roles of sulfur in energy metabolism. We conclude by looking at how the appearance of CoA allows us to harness energy released during the decarboxylation of alpha-ketoglutarate to form ATP directly during “substrate-level phosphorylation,” or, alternatively, to use energy from ATP to invest in the synthesis of heme.

chrismasterjohnphd.com/mwm/2/9

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