hey there again it's SRA peer for another episode of cancer as a mitochondrial metabolic disease I have been thinking about how I'm going to start addressing our audience I'm going to start addressing you as fellow mitochondriac I uh stole this from Dr Cruz who calls his members blacks one mitochondri acts but essentially we're all folks who are interested in mitochondria as being the root cause of many if not most or all chronic illnesses and how to optimize their functioning today we're going to talk about Cancer's other subst glutamine glutamine is a non-essential amino acid which means that our body can actually make glutamine but it has many essential functions which makes its targeting during mitochondrial metabolic therapy a little more nuanced unlike glucose which we can live off of ketones we cannot live indefinitely without glutamine so there is a in one of the papers that we're going to talk about a tug of war between cancer cells and normal cells especially immune cells so let's dive in so have we as we talked about and alluded to in several videos in the past when dealing with the warberg effect this graphic really is beautiful at illustrating what happens during the metabolic reprogramming that happens during cancer so under normal circumstances we have glucose you have it being trans transformed into acetyl COA it going through mitochondrial respiration the TCA cycle electron transport chain and you have some degree of glutamine being used for that process to support that process however during the metabolic reprograming that happens during cancer obviously glucose and the warberg effect is bringing in glucose about 30 times more than a normal cell we're producing a ton of lactate and that glucose is no longer getting into the TCA cycle to be used in oxid phosphorilation however glutamine is also increased significantly about 10 times more than a normal cell and it is being used to create several metabolic precursors to cell growth and division so as it talks about in this paper as knowledge of cell metabolism has advanced glutamine has been considered an important amino acid that supplies carbon and nitrogen to fuel biosynthesis a recent study provided A New Perspective on mitochondrial glutamine metabolism offering mechanistic insights into glutamine adaptation during tumor hypoxia the emergence of drug resistance and glut analysis induced metabolic reprogramming and presenting metabolic strategies to Target glutamine metabolism cancer cells in this review We introduce the various biosynthetic and bioenergetic roles of glutamine based on the compartmentalization of glutamine metabolism to explain why cells exhibit metabolic Reliance on glutamine additionally We examined whether glutamine derivatives contribute to epigenetic regulation associated with tumor Genesis so what we're seeing is that the metabolic reprogramming of the cell during the transition from normal metabolism to the warberg effect will upregulate the use of glutamine to provide backbones of important chemicals that cancer cells need for rapid growth however this is another vicious cycle that we're seeing is that increased use of glutamine and glutamine uptake is also driving this altered metabolism of cancer cells as well increased glutaminolysis is now recognized as a key feature of the metabolic profile of cancer cells along with increased aerobic glycolysis the warberg effect in this review we discuss the roles of glutamine in contributing to the core metabolism of proliferating cells by supporting energy production and biosynthesis so this is one of the important roles that Dr C free talks about in his lectures and his books and papers is that OT warberg the Nobel laurate that is responsible for discovery of what is known as now the warberg effect he only knew about at the time in the 30s and 40s about the use of glucose as fuel however it has been later elicit and reproduced many times that glutamine is the other secondary important fuel source for cancer cells glut analysis a Hallmark of cancer metabolism glutamine is the most abundant circulating amino acid in Blood and muscle and is critical for many fundamental cell functions and cancer cells including synthesis of biom metabolites that maintain monoch condal metabolism generation of antioxidants to remove reactive oxygen species synthesis of non-essential amino acids purines Pines those are important for DNA and RNA synthesis and fatty acids for cellular replication and activation of cell signaling so what we're also seeing is that glutamine via the release of ammonia is another way that hip one is stabilized and creates another non oxygen related pseudo hypoxia so this is causes and consequences of a glutamine induced normoxic hi1 activity for tumor metabolism under normoxic conditions normal oxygen conditions hip fan activity was significantly increased by glutamine metabolism which was associated with the release of ammonia so this is a fairly busy slide here but what we're seeing here is that glutamine is releasing ammonia ammonia is then activating pyruvate dehydrogenase chinise which blocks pyruvate dehydrogenase and blocks pyruvate getting into the TCA cycle in addition because of the lack of acetyl COA leads to a normoxic hip one Alpha stabilization and as we know and talked about in several videos when we stabilize hiff we're able to upregulate several processes that lead to cancer and the warberg effect glucose uptake and lactate dehydrogenase increase which then leads to the dreaded acidic tumor micro environment which then creates another snowball which further activates hiff and round and round it goes so I hope that you're seeing through these videos that unfortunately cancer is complex even when looked at from what I believe to be the more simplistic view as a metabolic or mitochondrial metabolic disease there are a combination of Vicious Cycles glutamine that drives tumor metabolism glutamine that stabilizes hiff through pseudo hypoxia several other factors that can contribute to the stabilization of hiff and pseudo hypoxia as we've seen in Brier photos part of the tumor micro environment and part of the tumor structure there are more normoxic and more hypoxic areas of the tumor architecture and so we have a lot of barriers to overcome but kind of zooming out a little bit if we can number one get into a state of ketosis where you have low amounts of glucose circulating and you know how to stabilize hiff through several different mechanisms which we'll talk about in the future and we've already talked about whether it be thyine repletion whether it be vitamin C whether it be providing sufficient oxygen Etc and if we have targeted strategies as Dr CPR talks about in his press pulse protocols to safely and non-toxic inhibit glutamine transport into cells and glutamine utilization in the KB cycle we have what seems to be a winning strategy at the metabolic management of cancer as I alluded to in the very beginning part of this video there is a tug of war that happens between Cancer and normal cells both need it and so it's not the same as I spoke to earlier it's not the same as ketosis ketogenic diets blocking portions of the glycolysis pathway which is used in mitochondrial metabolic therapies that is of less consequence because we have ketones that can function as alternative fuels however we cannot drastically affect glutamine for a long period of time without causing secondary toxicities and detrimental effects of the body so as we get through these videos we're going to be talking about these strategies that are being proposed and being used in alternative cancer clinics around the world as a way to starve cancer of glutamine with as little toxicity to the rest of the body as possible if you like videos like this please like comment subscribe and share with friends and family until next time