10:35:25 From Alaksh Choudhury to Everyone : are there conserved protein subunits that execute these common reactions? 10:44:51 From Fox Baudelaire to Everyone : the proteome 10:50:49 From Akorede Seriki to Everyone : Is the ATP generated in catabolic pathways the same as that used as building block for DNA? 10:51:04 From Roni Saiba to Everyone : Yes 10:51:19 From Akorede Seriki to Everyone : Thank you 10:51:43 From Roni Saiba to Everyone : Welcome 10:53:52 From Cristal Zuniga to Everyone : How complex is for a microorganism to take ATP from another? You mentioned Rickettsia is this mediated by very special transporters unique in bacteria ? 10:54:13 From Srividya Iyer-Biswas to Everyone : Terry, do I understand your question correctly — why is this percentage insensitive to the single-cell growth rate (which in turn reflects quality of growth condition)? And the answer — this % seems to be independent of growth rate. 10:55:37 From Terry Hwa to Everyone : Sri: actually the catabolic fraction of proteome expressed does change quite a bit for e. coli, but the ones that are actually needed are quite small. This is a 2-hr discussion all by itself. 10:57:36 From Terry Hwa to Everyone : @Crystal: what do you mean by “take ATP”? cells usually keep their metabolites unless there are ‘problems”. 10:59:15 From Zahmeeth Sakkaff to Everyone : If its an uptake how this calculation works? 10:59:53 From Caroline Holmes to Everyone : Can you make the presentation full screen? It’s hard to read. 11:02:29 From Muhammad Hasan to Everyone : Sorry, I have a question about the beginning section, I know that if there exist a conserved set of amino acids in the same group of protein, that amino acids belong to the same functional of this protein, but what if some of these amino acids mutate to another one ( that's structurally nearly same, for example originally it is valine and mutates to isoleucine in other protein) can we say that the same functional still exist ? 11:04:13 From Mikhail Tikhonov to Everyone : Could you comment on "follow the electrons"? As a physicist, I always fall back on the confusion "but charge is conserved!" What does it mean that "an electron must go somewhere"? 11:05:19 From Erin Olsan to Everyone : If one molecule loses and electron, then another molecule must take it up (one molecule is oxidized, therefore another must be reduced) 11:06:40 From Akorede Seriki to Everyone : Does ‘flux’ refer to the flow of substrate or energy? 11:07:44 From Ramis Rafay to Everyone : flux of both mass and energy (not necessarily limited to substrate) 11:08:46 From Rory Gordon to Everyone : What happens to the proton after it is transferred? 11:11:38 From Kapil Amarnath to Everyone : What’s wrong with having excess NADH in the cell? Is the problem that the cell can’t have ‘loose electrons’ causing unwanted reactions? 11:12:30 From Terry Hwa to Everyone : @kapil: need to balance the flux of electrons 11:12:33 From Alaksh Choudhury to Everyone : Based on your comment on Yatp In the light of evolution, could there be significant differences between the efficiency of the fermentaitive pathways between facultative fermenter versus an obligate one? 11:13:19 From Kapil Amarnath to Everyone : K so bottom line is just need a redox driving force 11:16:12 From Akorede Seriki to Everyone : Can we say that single carbon compounds like methanol are very reduced & thus have received lots of electrons? Is there any benefit to that? 11:18:47 From Alejandra Alvarado to Everyone : are there specific mechanisms that drive the location of metabolites within a cell, a microbial cell, -if as mentioned, these metabolites aren't just diffusing through the cell. 11:20:44 From Ilija Dukovski to Everyone : Does it mean fermentation defined this way is always anaerobic? Regardless if Oxygen is used by the organism or not. 11:21:36 From Caroline Holmes to Everyone : Ok, I think I’m more confused after the basic chemistry explanation. Glucose is not charged, right? And CO2 is not charged? How can you lose electrons and not change the charge? 11:21:37 From Terry Hwa to Everyone : @llija: no. a cell can choose to dump electron on oxygen or internally generated metabolites. 11:22:20 From Ilija Dukovski to Everyone : @Terry: thanks 11:25:19 From Matti Gralka to Everyone : @Caroline: my understanding is that the focus is exclusively on the C atoms not the molecule as a whole 11:25:23 From Melissa Fritz to Everyone : @Caroline I think the comparison of lose/gain is looking specifically at which atoms they are associated with within a bond. 11:26:38 From Melissa Fritz to Everyone : @Caroline When carbon is bound to oxygen, the electrons "belong" to the oxygen. When carbon is bound to hydrogen, the electrons "belong" to the carbon. 11:26:57 From Ilija Dukovski to Everyone : Considering the questions of charged molecules, think of it how close the electrons are to the carbon. That's it. They can be super distant, that's a charged ion. 11:28:04 From Ilija Dukovski to Everyone : So it is all about the wave function ofnthe electorn, is it "closer" to the Oxygen or the Carbon. 11:28:57 From Caroline Holmes to Everyone : Thanks everyone! That’s helpful 11:33:28 From Rory Gordon to Everyone : Are the terms “electron” and “hydride” interchangable in the biological context? 11:34:54 From Ilija Dukovski to Everyone : What is A typically in photoautotrophy? 11:37:18 From Rachel Gregor to Everyone : @Rory I wouldn’t say it’s interchangeable but it’s a good rule of thumb, generally more reduced has more hydrogens, more oxidised has more oxygens in the biologically relevant compounds 11:38:22 From Ramis Rafay to Everyone : @Illija molecular oxygen. Energy from photons absorbed is used to split H2O into molecular oxygen and protons 11:39:10 From Ramis Rafay to Everyone : This is the energy production side of photosynthesis (the light dependent reaction) 11:41:49 From Rory Gordon to Everyone : @Rachel Thanks! 11:45:07 From Ilija Dukovski to Everyone : Thanks. 11:52:09 From Matti Gralka to Everyone : technical comment: Alfred's voice is quite distorted on my end, as if the mic is set up too loud (he is also much louder than, e.g. Terry) 11:52:21 From Daan de Groot to Everyone : Is there a good syllabus on how to use redox balances in metabolism? 11:52:50 From Daan de Groot to Everyone : It is probably easier for everyone to read it at their own pace 11:53:05 From Matti Gralka to Everyone : that's much better thanks! 11:53:06 From Eiad Hamwi to Everyone : This is better! 12:00:04 From Matti Gralka to Everyone : I can hear Terry 12:00:06 From Andrea Giometto to Everyone : We can hear him 12:00:07 From Mikhail Tikhonov to Everyone : we can hear Terry 12:00:08 From Deepan Thiruppathy to Everyone : we can hear terry 12:00:10 From Ilija Dukovski to Everyone : I can hear Terry 12:02:59 From Ilija Dukovski to Everyone : If it is not heat, it is work :) 12:06:30 From Ramis Rafay to Everyone : Its more like 'dissipation' 12:07:33 From Ramis Rafay to Everyone : but probably yes, work is a way to look at it. But its not like 'useful work', if that makes sense. 12:13:19 From Justus Fink to Everyone : can someone remind me what P_i is? 12:13:23 From Ilija Dukovski to Everyone : Good point about "useful", it is useful only in context of fitness? 12:13:31 From Ilija Dukovski to Everyone : Phosphate 12:13:42 From Justus Fink to Everyone : thanks! 12:13:42 From Akorede Seriki to Everyone : Inorganic phosphate 12:13:45 From Roni Saiba to Everyone : inorganic phosphate 12:18:18 From Scott McCain to Everyone : Is the top example necessarily considered the most 'efficient', given it also needs to use more proteins? 12:19:01 From Ramis Rafay to Everyone : its more efficient because you translocate more protons for a given input of electrons transferred 12:21:16 From Daan de Groot to Everyone : @Scott, Fair point, I think. I guess you can define 'efficiency' in many ways 12:22:27 From Ramis Rafay to Everyone : indeed there is some capital cost investment in order to be more efficient, in some sense 12:23:43 From Justus Fink to Everyone : So inefficient pathways are faster because they have less steps or have similar steps but can skip ATP production (which slows you down)? 12:24:29 From Mikhail Tikhonov to Everyone : Is it obvious that the flux J_S should be proportional to dG? Or is that somehow a natural assumption given that if dG=0, then J_S is zero?.. 12:24:54 From Mikhail Tikhonov to Everyone : Abiotically, presumably there is no reason for there to be a correlation between reaction yield and the kinetic rate 12:26:49 From Daan de Groot to Everyone : I think that you indeed have this proportional relationship at least for near-equilibrium reactions 12:26:51 From Ashish B. George to Everyone : I think the original assumption for the linearity was justified as a taylor expansion for small Delta G (which is common in anaerobic conditions) 12:27:59 From Erik van Nimwegen to Everyone : @Daan what is the underlying reason for this relationship? 12:28:46 From Daan de Groot to Everyone : I think it is based on the Taylor expansion as Ashish stated, but I'm trying to look up an explanation now, because I forgot about the details 12:29:16 From Mikhail Tikhonov to Everyone : Abiotically, there would also be the Arrhenius law, right? So a whole new parameter (activation energy) which could in prinicple be anything. It sounds like an assumption that is specifically biological? (I might be completely off) 12:29:52 From Nicholas Noll to Everyone : Presumably it's related to the constraint that the ratio of the compounds are related to exp(-deltaG) at equilibrium which constrains the rates, no? 12:29:54 From Matti Gralka to Everyone : is there a way to predict (i.e., from the genome and resulting metabolic model) which pathway will be used under different conditions (e.g., high vs low glucose)? 12:30:02 From Vadim Patsalo to Everyone : Ecoli also have these pathways as L lactis, but don't make the same tradeoff depending on glucose concentration. Why? 12:30:04 From Ophelia Venturelli to Everyone : Do all organisms have the ability to operate in “rate mode” vs. “yield mode?” 12:30:13 From Ilija Dukovski to Everyone : Arrhenius law same here I believe. 12:31:10 From Otto X. Cordero to Everyone : I once went into the rabbit whole of trying to understand in detail Pfeiffer and Bonhoeffer’s paper, or the Costa paper referenced by Alfred. The real primary reference is in Heinrich and Schuster’s work, from the 80s. They have a book called metabolic controlled theory (the precursor of FBA). If memory serves me well, it’s all in chapter 5. I thought I would share in case someone wants to learn more about this. 12:31:32 From Otto X. Cordero to Everyone : *metabolic control theory 12:32:01 From Erik van Nimwegen to Everyone : Thanks Otto. Like Mikhail, it seems to me also that rate depends on activation energy, which is not necessarily related to deltaG of the reaction. 12:32:03 From Mikhail Tikhonov to Everyone : Thanks, Otto! 12:33:04 From Mikhail Tikhonov to Everyone : It seems like there was a section of the slides titled "Relation between thermodynamics and kinetics", maybe that's where it would have been explained? 12:33:18 From Ashish B. George to Everyone : Thanks Otto. that was helpful 12:33:18 From Mikhail Tikhonov to Everyone : Will look up the reference. 12:33:26 From Daan de Groot to Everyone : In this paper, they mention a relation between the ratio of forward and backward flux and the Gibbs free energy in the Introduction. Equation (4) should give it https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0000144 12:35:30 From Ashish B. George to Everyone : @Daan I think the people are interested in the difference between the fluxes, not the ratio 12:35:51 From Daan de Groot to Everyone : Well, those two are related, right? 12:36:53 From Ramis Rafay to Everyone : how much bigger or smaller one is in relation to the other can imply the difference between them, no? @Ashish 12:39:30 From Tyler Myers to Everyone : In a flux balance analysis, how to we make considerations for the change in flux for H2, given a mixed culture with Hydrogenotrophic methanogens? 12:40:43 From Ramis Rafay to Everyone : Intuitively the way I understand it, when you have a large amount of energy available to process, you can afford to go fast and 'dirty' and waste a lot of energy. But when energy is scarce, you need to be much more efficient with it, and in doing so go slower and try to waste as little as you can. 12:40:45 From Ashish B. George to Everyone : @Daan, @Ramis: I don’t think that is obvious. I think one can have very different net fluxes with the same ratio. The net flux would in principle depend on the activation energy while the ratio would depend on the Delta G. 12:42:11 From Otto X. Cordero to Everyone : I think those two explanations (proteome allocation and Pfeiffer Bonhoeffer) are not too different, as I understand them. What Heinrich and Schuster did was define a linear pathway and ask what is the optimal enzyme allocation under two constrains: fixed enzyme concentration and fixed intermediate concentration. Total fixed enzyme concentration implies proteome cost 12:48:13 From Mikhail Tikhonov to Everyone : @Ashish exactly 12:49:47 From Ramis Rafay to Everyone : Its true that there is one degree of freedom from ratio to absolute flux. I imagine though that would be the known or assumed concentration of a reactant and/or product. 12:51:57 From Caroline Holmes to Everyone : I think that that degree of freedom is activation energy, no? 12:54:09 From Zahmeeth Sakkaff to Everyone : Is this recording will be available? If yes, where I can watch the video 12:54:36 From Terry Hwa to Everyone : same link where you registered for this forum 12:55:29 From Kavli Institute for Theoretical Physics to Everyone : @Zahmeeth Recording will be posted at: https://online.kitp.ucsb.edu/online/metabolism-oc21/ 12:55:37 From Daniel Segre to Everyone : Here is a paper I find useful, and I think is relevant to this discussion: https://pubmed.ncbi.nlm.nih.gov/23892083/ 12:55:50 From Zahmeeth Sakkaff to Everyone : Thanks! 12:56:20 From Mikhail Tikhonov to Everyone : Ooh, that looks excellent. Thanks, Daniel! 12:56:32 From Ramis Rafay to Everyone : @Daniel thanks! 12:58:31 From Ashish B. George to Everyone : Thanks, Daniel! 13:00:01 From Zahmeeth Sakkaff to Everyone : Thank you soo much! 13:00:08 From Eammon Riley to Everyone : Thank you! 13:00:10 From Otto X. Cordero to Everyone : Thank you, Alfred and the organizers 13:00:13 From Emily Armbruster to Everyone : Thank you! 13:00:14 From Kapil Amarnath to Everyone : Thanks! 13:00:17 From Bethany Kolody to Everyone : Amazing talk! Thank you so much 13:00:18 From Korin Jones to Everyone : thank you! 13:00:19 From Emily Zakem to Everyone : thank you!! 13:00:23 From Malaika Ebert to Everyone : Incredibly interesting, thank you so much! 13:00:23 From Allison Coe to Everyone : Thank you! 13:00:23 From Hector Hernandez Gonzalez to Everyone : Amazing talk. Thank you very much!! 13:00:25 From Melissa Fritz to Everyone : Thank you so much! 13:00:36 From Gabriel Mullin-Manzanarez to Everyone : Thank you for the talk! 13:00:40 From Lucas Le Nagard to Everyone : Thank you so much! 13:00:41 From Martin Jahn to Everyone : This was a fantastic introduction ! 13:00:44 From Alejandro Bonive to Everyone : Thanks! 13:00:45 From RICHA SHARMA to Everyone : Thank you so much Alfred for the wonderful talk!! 13:00:51 From Sarah Ardell to Everyone : Thank you so much! This was incredible! 13:00:52 From Griffin Chure to Everyone : Maybe a course slack workspace? 13:00:53 From Daan de Groot to Everyone : Thanks for organising this! 13:01:11 From Eric De Giuli to Everyone : Slack or Discord can be used for discussions 13:01:33 From Andrea Giometto to Everyone : Thank you! 13:01:34 From Petra Steffen to Everyone : Many thanks from Germany 13:01:38 From Zachary Landry to Everyone : Slack would work