Across these recordings, you will hear about the polar metabolites and the lipids that make the hearts of fourteen Metabolomists beat for their research.
In this special episode, we learn more about pyruvate, gamma-hydroxybutyric acid (GHB), glutathione, branched-chain alpha keto acids (BCKAs), tryptophan, glutamine, glutamate, nicotinamide adenine dinucleotide (NAD), nonanal, strychnine, daptomycin, but also free fatty acids, oxylipins, sphingolipids, and acylcarnitines.
A big thank you to all the contributors!
Make sure to let them know that you share their passion for their favorite metabolite by connecting with them with the links below.
Sara Abdulkader, Weill Cornell Medicine (Qatar) (https://www.linkedin.com/in/sara-abdulkader-5a7b8417a)
Iman Achkar, Weill Cornell Medicine (Qatar) (https://www.linkedin.com/in/iman-w-achkar-523a1b90/)
Jerzy Adamski, Metaron Diagnostics (Germany) (https://www.linkedin.com/in/jerzy-adamski-14305665/)
Anna Halama, Weill Cornell Medicine (Qatar) (https://www.linkedin.com/in/anna-halama-0a23a36a/)
Michal Kaczmarek, Blatvatnik Center for drug discovery (Israel) (https://www.linkedin.com/in/kaczmarek-michael/)
Jennifer Kirwan, Berlin Institute of Health (Germany) (https://www.linkedin.com/in/jennifer-kirwan-b20947194/)
Christoph Magnes, Johanneum Research (Austria) (https://www.linkedin.com/in/christoph-magnes-a4465719/)
Sophia Moco, Vrije Universiteit Amsterdam (Netherlands) (https://www.linkedin.com/in/sofiamoco/)
Parisa Mottaghi, Imperial College London (UK) (https://www.linkedin.com/in/parisa-mottaghi-64b06a110/)
Pierre-Hugues Stefanuto, Université de Liège (Belgium) (https://www.linkedin.com/in/phstefanuto/)
Justin J.J. van der Hooft, University Wageningen (Netherlands) (https://www.linkedin.com/in/jjjvanderhooft/)
Craig Wheelock, Karolinska Institute (Sweden) (https://www.linkedin.com/in/craigwheelock/)
Qi Zhong, Imperial College London (UK) (https://www.linkedin.com/in/qi-zhong-b7249a10b/)
Laimdota Zizmare, University Hospital Tuebingen (Germany) (https://www.linkedin.com/in/laimdota/)
in this very special episode of the metabolist we went on the road and asked many of you to share your favorite metabolite with the rest of the community the interviews in this episode were all recorded at the annual meeting of the metabolomic society that took place in Valencia Spain in June of 2022 this meeting was a special one as it marked the return of medok as an inperson meeting and I took this opportunity to meet as many of you as possible to introduce the podcast and to collect your impressions if you follow me on LinkedIn you know that I was frantically looking for volunteers to share their favorite metabolite on the air I already published a few of these interviews on my account and this episode combines the contributions of all the lovely people who accepted to chat with me about their love of metabolites I want to thank each and every one of the brave people who spoke with me for this episode thanks to Craig hustin she Parisa piug Jennifer Kristoff Iman Sarah Anna Sophia mishelle urek and lime for taking the time to chat with me during this intense week it takes some courage to expose your passion about your work in the way that they did but this is something we all get used to as scientist we had an amazing time at the conference and I hope that we can repeat this experience soon at the next inperson meeting in in the meantime I hope that you enjoy listening to this episode as much as we enjoyed creating [Music] it the metabolist is the podcast where scientists connect to explore the unspoken issues in metabolomics research I am your host Alis Lionel and together we will examine how metabolomic data interpretation is done I will discuss with other metabolists how they do this work how they plan execute but also communicate metabolomics my name is Craig wock and I work at the kolinska institute in Stockholm Sweden and then part-time at GMA University in Japan very well and so will you share with us your favorite metabolite and why it’s your favorite metabolite perfect it’s hard to pick one so my favorite class of molecules I work on on the oxy lipins these oxidized products of polysaturated fatty acids and particularly the octadecanoids which which are the c18 subclass of oxy lipins and if I had to pick one specific molecule within that class it would be something called a 1213 diome this is a visal diol product of linolic acid it’s produced by oxidation by satome p450 to the epoxides which are then cleaved by the soluble epoxide soluble epoxide hydrolat to the corresponding visal dials this compound been around for a while it was first reported by Japanese group Ozawa and colleagues in the 80s to be produced in response to acute respiratory distress syndrome or ards so if they looked at ards Patients they would see you know um massive pulmonary edema occurring with ards and they see increased levels of these compounds and they did a number of animal studies where if you injected the precursor the epoxide into rats within 10 minutes you see this massive pulmonary edema in these rats so the compound back then was called lucco toxin was the epoxide and then luoxin dial because it was toxic to lucites there’s since it’s lenic acid there’s two different isomers of this there’s the 910 and the 1213 the 1213 is my particular favorite that one’s called isolat toxin or isolat toxin dial when I started my PhD the year after I started my major Professor Bruce hammock he published a m paper in nature of medicine they came out and looked at the bioactivation of molic acid epoxides the these dials and they found that one is increased again in ARS patients and two is that they could blate the toxicity by using an inhibitor of the soluble epoxy hydrolat to prevent the epoxide to dial conversion so that’s how they knew that the epoxide was a quote protoxin and that it was actually the diol that was causing the toxicity which oaan colleagues didn’t know and so my old boss he spent decades studying this enzyme and now it’s nothing really happened since the 1997 paper and then Flash Forward uh to quite recently and um there’s been a string of of papers come out at the 12113 diome look in PubMed there’s a number of papers in you know nature medicine looking at this that it’s important in brown fat activation it’s uh development of immune tolerance and asthmatics cardiovascular disease whole range of things that’s showing that actually this is a very potent bioactive lipid yeah that’s a lot of very interesting fi so I guess this is where get a lot of people interested who are listening thank you very much thank you [Music] hi my name is lime datar however I prefer to be lime like the fruit and I’m working in University Hospital tubing in near stutgart in Germany and I’m doing preclinical and clinical metabolomics research by anmr spectroscopy thank you so what is your favorite metabolite and why lately my favorite metabolite has been pyro because it’s like me it’s a multitasker it’s involved in more than 50 different sub metabolic pathways most popular being the TCA cycle like colesis phosphate pentos phosphate pathway it’s in the center of everything and I think it’s underappreciated thanks and do you study it in specific context in your research I get to study it quite a bit because some of the research that I’m involved it’s really around the energy metabolism and Pur has become really the central homework and gatekeeper for a lot of Pathways that I get to investigate and I think it’s really exciting thanks a lot and good luck thanks a lot [Music] my name is MI kadic I currently work in Tel Aviv in the blavatnik center for drug Discovery I’m working at the metabolite medicine division where I take care of the analytical chemistry and all the metabolomics both targeted and targeted perfect and so now what is your favorite metabolite and why please so this is a good question definitely the favorite needs to be defined for me the favorite will be with my favorite background story so here I would choose the one that actually it’s interpretation of physiological levels affected lives of many peoples and this brings me all the way back to my days where I was working the forensic toxicology space and this metabolite is uh gamma hydroxy butc acid it’s usually abbreviated as GHB is a short chain fatty icid it’s usually denoted as neurot transmitter neuro modulator you can find it in brain and it’s all the like it’s all the produced by G Gaba it’s gamma amino butc acid and it was also known as anesthetic drug it was synthesized in 1960s but it wasn’t really long in Ed because it had a side effects like a pain or delirium so later on it was illegally misused for Dr Ro facilitated crimes because the anesthetic effect was really strong and um also because people who are intoxicated with GHB offers suffer from Amnesia they uh it was used by criminals for sexual assault cases and because this is the compound that is both endogenous and can be exogenous as you can probably see the interpretation of this could be quite challenging and in addition to that the metabolism of GHB the metabolism is very rapid so the maximum concentration is usually achieved within 30 to 90 minutes after the oral intake and you can detect It in Blood usually within 6 hours that was the rule of a farm and in urine within 12 hours on top of that all the forensic Laboratories had to themselves Set uh cut of value and above the cut of value the level of the GHB was treated as exogenous this was quite challenging part to do because different people depending on their age the physical activity the gender they had different physiological level even without an exposure to GHB uh and uh after more research was done another layer of complexity appeared which is uh postmortem redistribution and in vitro production so depending on the storage conditions on the temperature on the type of additives the GHB could basically be produced within the already collected sample and this caused a lot of troubles and let’s say cord interpretation so the expert opinions from couple of years back in the days are not valid anymore today okay which is a fascinating Story So currently what people are doing they’re uh researching The Phase 2 metabolizer of GHB to maybe find a more reliable biomarker of the external use of GHB and uh somehow this this GHB is always circling back to me so even when I was doing research outside of the forensic toxicology space it was being said to be a signaling molecules in living organism Al in plants in animals in bacteria and even in my current project at the blavic center for drug Discovery we’re trying to establish the human metabol database and of course we included GHB there among another like thousand other compounds there so it’s quite a fascinating metabolite for me personally thank you very much you really like give flesh to the story of the metabolite it really makes it interesting and I think it’s particularly interesting when you have metabolites that are both endogenous and taken exogenously even if it’s against your will thank you very much hi my name is sah Abdul Kad I’m currently working at whale Corel medicine in Qatar and I’m also pursuing my PhD with the Paris clay University in France and the topic of my PhD is uh disregulated metabolism of branchin amino acids in different cancer cells thank you so what is your favorite metabolite and why so of course my favorite metabolite is part of the bran chain amino acid pathway and it’s the bran chain Alpha keto acids which are product of uh the catabolism of the bran chain amino acids and it’s also one of my favorite metabolis because these metabolites are expressed differently in different cancer cells and also the expression of the enzymes that are responsible for these metabolites are also expressed different differently in different cancer types so if we try to Target these enzymes we could that could be one of the treatment strategies for different cancer cell lines especially lung cancer cell lines okay you work especially on lung lung cancer we work on lung cancer and breast cancer is there any other aspect that you that you find interesting about Branch amino acid in general in general the enzymes on the branchin amino acid catabolic pathway are expressed differently in different cancer cell lines so we are looking at other enzymes on the catabolic pathway and we’re seeing by inhibiting some of these enzymes has an effect on these cancer celles or not so we actually found that uh the high metastatic potential sunell lines enhanced branching amuno acid catabolism as compared to low metastatic potential cell lines okay so this has a lot of promise for treatments I guess hopefully and this is what we’re working towards so thank you very much thank you I’m y adamski I’m Professor Meritus at hamood Centrum munan and I’m a chief scientific officer of meton Diagnostics thank you and so what is your favorite metabolite at the moment and why today I would like to bring to your attention the C4 and C5 asil carnitines Bal and isov carnitines and this is because how they have emerged in the metabolomic studies worldwide first they have been picked as a marker of inore error of metabolism and are being used in diagnosis of isar atil COA dehydrogenase however later on the levels of these two biomarkers were associated with prey diagnosis of disease a bowel disease uh for people who are ingesting gluten and this could be easily used for the differential diagnosis to identify what is the reason for immunological reaction the second very important part is that these two ail carnitines do not rather reflect a short chain fatty acids but they reflect amino acid metab abolism especially that of brain chain amino acids so brain chain amino acids BCAA they are associated with uh insulin resistance and uh are Hallmarks of transaminase inhibition that’s why if you’re seeing the changes in the C4 and C5 Sil carnitines this is not exactly change in the lipid metabolism but rather in the amino acid metabolism thank you that’s really interesting thank you my name is Sophia mosu and I work at FR University in Amsterdam thank you and what is your favorite metabolite and why my favorite metabolites is nicotinamide adinin nucleotides and I have been working on this molecule and the health effects of this molecule for the past four years so this is a for me a quite interesting molecule because when I started working on it I thought you know how can it be that there’s still so much research to be done on a very old known redox cofactor so NAD plus and its reduced form nadh are participate in hundreds of metabolic reactions throughout metabolism involved in glycolysis TCA cycle but also on all kinds of other other biot Transformations uh um in addition to this very known biochemical feature uh more recently NAD was found to also have some signaling properties in the way that it is a substrate of proteins like CNS and in that way it can it can have different type of effects in terms of health so what is interesting is that within metabolic diseases more and more researchers are are finding that Ned levels decrease with age deficient Ned levels are found in diabetes and a chronic kidney disease for example or fatty liver disease and that increasing levels of NAD then leads to a better mitochondrial function and better health benefits so I have been working for the past years on studying different Ned precursors that can boost levels of Ned in animals and then with the idea that this can once be translated in into humans thank you so you’re looking into all the new prospects for NAD research thank you very much for sharing thank you very much hello my name is Kristoph Magnus I am the head of the metabolomics group at Yim research uh we are located in Gratz Austria and here we are working is in this field for more than 15 years I think now what’s your favorite metabolite and way I thought a little bit about that and I came to an end and say my favorite metabolites are at the moment free fatty acids why we have several studies where we found interesting patterns for example for uh diagnosis of pulmonary hypertension this is a cooporation project we had with Medical University in Gratz professor oesi and we tested very small group only four controls and four matched patients with uratic arterial hypertension and we found a very very specific fatty acid pattern only in this small group and we were able to validate this in a larger cohort afterwards and it’s very interesting that there are such big difference in in the free fatty acid pattern and we can use that for early diagnosis fatty acids can be incorporated in bigger molecules bigger lipids do you see anything on patterns for bigger lipids did you look into this we didn’t observe the incorporation now what we saw is the biomarker works very well if we put this free fatty Attis in relation to larger lipids for example this is something which works very well we are performing now mechanistics studies with the groups there are different hypothesis why we have this uh different free fatty acid patterns it might be that there is a damage in mitochondria in the heart but we are now uh searching for the the right answer to that super that sounds wonderful thank you very much Kristoff and I wish you a good conference thank you very much my name is Dean ashkar and I’m conducting the research at whe Cornell and Qatar and this is in collaboration with the Technical University in Dresden Germany I’m involved in further investigating altered cancer cell metabolism specifically in lung and breast cancer cells thank you so what is your favorite metabolite and why I would say my favorite metabolite is glutathione specifically because it’s involved in overcoming oxidative stress in different cancer cells so my work is predominantly focused on that pathway and what’s interesting is that you can find different types of cancers which have a high antioxidative potential so the idea is that potentially we could Target this and exploit this feature by targeting glutamine metabolism uh by introducing different agents for example component 968 which could Target glutaminase and by default hamper cancer cell’s ability to overcome oxidative stress interestingly enough you could also introduce other agents which induce oxidative stress for example doxorubicin and the idea behind that is to accelerate cancer cell death and I guess one question that comes to you often is is glut is found in every cell so how do you target the cancer cells specifically that’s a very good question it’s been found that cancer cells can depend heavily on glutamine and because of that you can exploit this feature to selectively Target cancer cells over normal cells thank you very much thank you my name is just ther host I’m an assistant professor in computation of metabol and I work in V at V University thank you and so what is your favorite metabolite and why so it’s a very hard question and very challenging I’m almost 15 years active in metabolomic so I’ve seen a lot of metabolites but recently I’m more a bit more inter products and then dyin is a really nice example of an early found really successful antibiotic it’s a lipopeptide so with its structure of an an circular peptide and an Asal chain it is a potent way of killing specific bacteria and it was inspired by Nature so that is also very inspiring for the field so is it a synthetic molecule or is it a natural product the original molecule was we isolate as a as a natural product from if I not incorrect stratto misis bacteria okay but another remarkable example is stenine not only because it’s potent bioactive right but if you look at the size of the molecule and the complicated structure it is an example of how incredibly creative nature can be so very interesting so these are two metabolites then you cheated a bit I think as a scientist we we should always try to at least a little bit bend the rules and you know uh sometimes you get away with it and sometimes the experiment will fail as a consequence so let’s see what happens I think this one will work out good luck with the conference and thank you very much for your time my name is and I’m a PhD student from UK dementia Research Institute at imp hi my name is Parisi and and I’m a PhD student from Imperial College I’m also part of the dementia Research Institute at Imperial great what is your favorite metabolites and why uh my favorite metabolites is sper lipids because we are mainly working with Al disease and SLE lipids has been implicated like the change of SLE liid has been heavily implicated in um Alzheimer disease and also for the gene that we’re looking at which is the Africa 7 gen we also find out like recently there are changes of single lipid metabolism in the mice model and also in a human C we found the association with Lexa ceremon in particular and then what do you find so interesting about them so yeah as my friend said here the Lac ceramides is the lipid of interest because there’s a very high association with both in animal organisms as well as he models with clinical data thank you very much my name is Anna halama I’m from well Cornell Medical College in Qatar and I’m assistant professor there we are focusing as a research group on cancer and cancer metabolism as a potential predictor of future treatment strategies perfect thank you and so which one is your favorite metabolite and why well lately my favorite metabolite is glutamine and glutamate as a couple of metabolites which are my favorite because I believe they might change future treatment of cancer patients or maybe if not even that they might be used as a Tracker system for the responses to the treatment okay so in your research where have you seen them changing what what makes you so confident that these metabolites will be the future of This research what you observed is cancer cells some of them strongly depend on glutamine metabolism and they are using glut in as a fuel to further proliferate and to generate energy so this pathway is kind of crucial some of the cells instead of using glucose they are switching their metabolite off and they are starting to utilize glutamine this pathway can be easy blocked and there are already uh compounds which are in the clinic and they were showing success in blocking this pathway where the glutamine is changed to glutamate which is further incorporated into the ca cycle but cancer cells are very flexible in their metabolism and they are frequently changing this path and they are starting utilize other molecules which we also find in our study which was particularly fatty acid and they are starting to utilize beta oxidation and energy generated from those molecules so now the very important question and very important component of the study would be how to block those two Pathways in the same way uh to improve potential treatment strategy for those for those patients and there is an option because this was something which we were able to show in our previous study that indeed while blocking glutamine metabolism and simultaneously fatty acid catabolism we were able to accelerate cancer cell death so this is already certain promise right what is more important we were able to use the drugs which are already in the clinical setting like for instance triadin which is blocking the beta oxidation of fatty acid and another component which was also useful was chloro quinon chloroquin was blocking the autophagy which is also upregulated in response to blockage of this glutamine this is shortcut of why I feel glutamine and glutamide are very important wonderful thank you very much thank you very much hi I’m Pi Stefano I’m lead scientist at the University of in Belgium and I’m working mostly between the university for analytical chemistry and the hospital for all the metabolomic application thank you which one is your favorite metabolite and why so my favorite metabolite is a really small molecule called nonanal that we see in a lot of our studies so I mostly study exal breaths so really small volatile using multi-dimensional GC and nonanal is the one that I see everywhere I’m focused on lung inflammation and if I study plasma COPD fibrosis like non Nal is there so we don’t know why we don’t know where it’s coming from but that’s why it’s exciting so it’s our friend that we see everywhere but we don’t know where it’s coming from and we just want to learn more about it is there anything known about the use of the body from that metabolite or you think it maybe more comes from the outside any clues on this I think it’s a byproduct of lipid peroxidation because since it’s an alide we probably know that the lipids like through reactive oxy oxygenated species will produce this type of molecule but we don’t know exactly the pathway so there is like a lot of suspected pathway but because it’s so small it can come from basically everywhere so we have a large field of Investigation to try to understand that and it’s related to other type of Metabolic Research because they study like big lipids degradation and we are like oh they are doing that and nonanal can come from there so maybe we have to reach out and see if they see nonanal there and we have our own hypothesis that we are trying to test also so it’s really exciting that sounds really good thank you very much thank you very much it was a pleasure to talk to you I’m Jennifer Kerwin I work at the Berlin Institute of Health at the charate and what do you do there I lead the metabolomics technology platform thank you so what is your favorite metabolite and why tryptophan and I’m really interested in tryptophan because it acts as a direct link between nutrition the gut microbiome and human health and how does it do all of that so we’re only really just beginning to understand all the roles that trypan and its metabolites have in the body one of the things that we’re increasingly interested in studying is how and in which root tryptophan is metabolized so tryptophan is a fairly unique amino acid it is the largest amino acid and it has an indor ring and this indor ring is often used for signaling and it has a unique role in proteins so tryptophan is one of the rarest amino acids in proteins but where it appears it’s often got a really important signaling um component and it’s very common for instance in membrane proteins or or proportionately very common so that that’s one element of tryptophan which is is very interesting uh but we also find that tryptophan is metabolized by the gut M bacteria often to various forms of indol and these indol can have very positive effects particularly on the immune system but they can also have very negative effects indol cell for instance can be toxic in large amounts and it’s it’s metabolized by the human Li into indol sulfate which then acts as a kidney toxin human cells also metabolize stopan um and they tend to choose various roots to do this by but 90% of tryptophan is metabolized via the curine pathway and curine and its metabolites have really important roles on suppressing the immune system this is increasingly of importance when we’re studying autoimmune or immune mediated diseases such as multiple sclerosis and rheumatoid arthritis for example uh but we also find that tryptophan is metabolized into several important neurotransmitters so five hydroxy tryptophan or serotonin or melatonin and interestingly we find that serotonin for instance although we think of this as an important brain neurotransmitter about 90% of Serotonin is actually in the gut and we think this probably has a fairly important effect on gut motility I think there’s an increasing interest in how the gut and the brain are talking to each other and we’ve got lots to discover about this and we don’t yet know the full role of of cryptophane and its metabolites in this gut brain axis and how it’s impacting on our health it’s a fascinating molecule it really is thank you so do you think then Tri toan is the source of Happiness both for the gut and for the brain then we we’re happy because of Serotonin but we also have a happy gut thanks to trip to find indirectly well there’s an interesting question that I’ve never considered I would say like anything else it’s probably everything in moderation and very good point uh thank you very much for all this information about trip to fun there’s a lot more I’m sure that you could tell about it so I know that you you had a a talk today and you presented some interesting ideas so what did you discuss today so this is something completely different from trip toan um I’m a member of the metabolomics quality assurance and quality control Consortium and I was reporting on the results of working group that is interested in reporting standards for QA in QC for untargeted metabolomic so we think that that to report what you’ve done is particularly important it allows transparency of what you’ve done it allows your readers or your listeners to really understand the quality of your data and also interpret how robust and likely reproducible your results are and we think that this is really important an additional benefit of reporting your QA and QC methods and results are that it allows people who are new to metabolomics to quickly see what other people are doing in the field and start implementing that themselves and we hope that overall this this will mean a gradual incremental increase in the robustness and reproducibility of mixed data thank you very much thank you very much thank you for joining us in this discussion I hope that this episode gave you new insights and ideas on how to plan conduct and communicate your own metabolomic projects if you’d like to continue this journey with us make sure to register for the metabolist email list on the podcast web page for regular news on metabolomics and data interpretation you can connect with me Alis moel on LinkedIn where I post on metabolites analysis strategies data processing tools and more and make sure to check out our other podcast episodes on the metabolist website