Mastering Nutrition

This podcast explores the regulation of gluconeogenesis in the liver, highlighting its role in maintaining blood glucose levels and coordinating nitrogen disposal. It explains the various metabolic processes the liver engages in and compares the regulation of glycolysis in the liver and skeletal muscle. The podcast also explores the conversion of fructose 6 phosphate to fructose 2,6 bisphosphate and factors that affect pyruvate kinase activity. It discusses the regulation of gluconeogenesis and glycolysis based on glucose needs and liver energy resources.

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 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson.    

Explore the multifaceted role of insulin in energy metabolism, including regulating energy supply, influencing energy usage decisions, supporting thyroid hormone production, and defending against glycation. Learn about the importance of glucose in metabolic processes such as lactate production, fatty acid synthesis, DNA replication, and protein production, and how insulin acts as a sign of energetic versatility.

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 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson.

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! Access the show notes, transcript, and comments here: https://chrismasterjohnphd.substack.com/p/047-are-we-all-evolved-to-eat-high

This podcast explores the role of insulin in fat storage and synthesis, discussing its regulation of glucose uptake in skeletal muscle and adipose tissue. It debunks the myth that insulin alone causes weight gain, emphasizing that excessive food consumption is the main driver. The podcast also delves into the process of converting glucose into triglycerides in adipose tissue and the role of glycerol in glucose production by the liver.

This podcast explores how insulin affects the uptake and release of fatty acids, the role of enzymes in fat metabolism, and its impact on energy metabolism including the citric acid cycle, fatty acid synthesis, and carbohydrate and fat oxidation.

The podcast discusses the role of insulin in promoting glycolysis and glucose metabolism. It explores how insulin affects enzyme activity, glucose transport, and glycogen synthesis in skeletal muscle. The episode highlights the importance of insulin in burning glucose for energy when the cell's energy status is low. For more details, visit chrismasterjohnphd.com/mwm/2/24

Exploring the role of insulin beyond glucose regulation, including its involvement in protein and fat metabolism. Analyzing the relationship between insulin signaling, glucose metabolism, and nutrient transportation. Understanding the distribution of glucose and fat through glucose transporters and the activation and function of different tissues. Discussing the expression and function of LPL in pancreatic beta cells and its impact on insulin secretion. Exploring the different mechanisms that amplify insulin signaling, including anaporotic substrates and malonyl coa. Suggesting a potential connection between the pancreas, carbohydrate responsiveness, and the expression of transporters.

This podcast explores the regulation of fat burning and fatty acid transport, discussing the role of various membranes and enzymes involved. It highlights the significance of CPT-1 as the key limiting step, regulated by malonyl coa controlled by energy status. The dynamic regulation between fatty acid synthesis and beta oxidation in response to energy status is also discussed, as well as how high energy status in the cell can inhibit fat burning.