Prompt Cast
Understanding Metabolomics, NAD, and Cancer Metabolism with Josh Rabinowitz
TLDR Josh Rabinowitz delves into the intricate world of metabolomics, highlighting the importance of understanding metabolism in health and disease. He discusses the role of lactate as a fuel, the electron transport chain, and potential implications for drugs and nutrition in cancer metabolism.
Timestamped Summary
00:00
Josh Rabinowitz, a professor at Princeton University, discusses metabolomics, NAD, and cancer metabolism in a technical episode focusing on glucose metabolism, lactate as a fuel, the electron transport chain, and the implications for drugs and nutrition.
07:04
Josh Rabinowitz discusses his transition from medicine to full-time research, highlighting the appeal of pursuing novel scientific challenges over the repetitive nature of clinical practice.
14:15
Metabolism was initially considered a solved problem, but the rise of metabolomics and the increasing prevalence of metabolic syndrome led to a shift in perspective, highlighting the importance of understanding metabolism's role in health and disease.
21:37
Metabolomics explores the tightly regulated nature of metabolites in the body, with some behaving like pH and others showing active or passive regulation to maintain a healthy range in the bloodstream.
29:29
Glucose regulation is tightly controlled in the body, with even small deviations leading to significant health issues due to the delicate balance between glucose and fat utilization in tissues.
37:11
Lactate serves as a major circulating nutrient in mammals, with transporters allowing it to be used as fuel by various tissues in the body, providing flexibility and a universal form of carbohydrate energy.
45:01
The body's ability to use lactate as a flexible energy source, balancing redox problems and allowing for efficient energy distribution among cells, highlights the importance of lactate in metabolic processes.
52:30
Metabolic syndrome should be addressed earlier by looking for signs like lactate dysregulation as potential early indicators.
01:00:30
High energy bonds are created through a cycle that liberates chemical energy through electron transfer, with NAD and NADH playing a crucial role in maintaining the balance for proper metabolism.
01:07:59
Metformin may have a potentially deleterious effect by increasing lactate levels, while NADPH plays a crucial role as an energetic building material in various biological processes.
01:15:42
A decline in NAD levels with aging generates the hypothesis that restoring NAD levels in older organisms to those of younger organisms could improve performance, leading to the rise of NAD clinics offering intravenous NAD infusions due to the lack of oral absorption routes for NAD.
01:23:40
Niacin prodrugs like NR and NMN may not significantly impact NAD levels in tissues when taken orally, potentially due to delayed absorption forms and low circulating levels compared to nicotinamide.
01:31:07
The route of administration for hormone replacement therapy can impact cardiovascular risk, with oral estrogen potentially increasing risk compared to topical administration.
01:38:29
Josh Rabinowitz's journey from studying metabolism to oncology was influenced by a call from Craig Thompson, leading him to explore the connection between cancer cells' distinctive glucose usage and nucleic acid synthesis vulnerabilities.
01:45:45
Cancer cells can utilize various fuel sources, making it challenging to cut off their fuel supply without affecting critical functions like immune cell and brain fuel supply, suggesting a multifaceted approach targeting nucleic acid synthesis and applying stress to cancer cells' fuel supply may be a more effective strategy.
01:53:18
Pancreatic adenocarcinoma is difficult due to early metastasis, invasive nature, RAS oncogene mutations driving metabolic scavenging, and the cancer's ability to be lethal without being highly metabolically active, posing challenges for treatment approaches.
02:01:20
A discussion on the potential impact of dietary strategies, including ketogenic diets and timing of macronutrients, on cancer treatment and the importance of making interventions clinically actionable and simple for patients.
Categories:
Health & Fitness
