Tips for studying metabolism- things to focus on (e.g. logic, cofactors, reaction types, etc.)

Things to focus on in metabolism - logic is key! If you learn the core concepts and focus on the basic logical principles, you can then logic your way through all sorts of complex scenarios. Because metabolism is complex, but it is highly logical, and the same sorts of strategies and concepts play out over and over. So, rather than memorize, conceptualize…
What do you “want” to happen, where?
* Know what each main metabolic process “gives you”
* e.g. energy, nucleotide precursors, etc.
* Roles of different tissues (esp. liver & muscles) - put things in perspective to help predict what you want happening where when
* e.g. liver has to regulate blood glucose, but muscles just have to contract & stuff - so in response to adrenaline, liver makes or frees up glucose & ships out, whereas muscles just burn the glucose they get &/or free up for energy they can use for themselves
* Know which main metabolic processes can & can’t happen in which tissues
* e.g. only liver & kidneys can do gluconeogenesis; liver & muscles can do glycogenolysis
* Fuel preferences of different tissues
* e.g. liver prefers fatty acids, preventing it from hogging all the glucose it needs to provide to other tissues
How does that happen?
* Get comfortable tracking arrows on metabolic charts
* Main types of metabolic chemical reactions
* e.g. phosphorylation, dephosphorylation, other hydrolysis, condensation, isomerization, carboxylation, decarboxylation, oxidation, reduction
* Main cofactors
* e.g. NAD(H), FAD(H2), NADP(H), CoA, TPP, biotin, PLP
* Be able to recognize what types of reactions they’re used for
* Know which processes happen in mitochondria vs. cytoplasm
* e.g. TCA (as a whole cycle) happens in mitochondria, glycolysis in cytoplasm
* Know which molecules can & can’t enter/leave mitochondria
* e.g. oxaloacetate, CoA, NAD(H) can’t enter/leave
How does that happen where and when you want it to? (Regulation)
* Get comfortable tracking designations of inhibition & activation on metabolic charts
* Points of enzymatic regulation
* What and why - look for “irreversible” reactions (don’t want to “accidentally” go forward because you can’t regularly go back)
* These are typically controlled kinetically (i.e. regulating the enzyme directly)
* Physical types of enzymatic regulation:
* Allosteric - molecules bind enzyme & change its activity
* Know main ones
* What does their presence indicate?
* What enzymes are regulated by them?
* Why does the make sense?
* Look for what the enzymes regulated by it have in common
* Compare & contrast allosteric regulators of different enzymes
* Covalent - e.g. phosphorylation
* Know main metabolism-associated hormones (e.g. insulin, glucagon, adrenaline, cortisol)
* When are they made?
* Where are they made?
* Do only certain tissues respond?
* Know which hormones activate which kinases & phosphatases
* e.g. glucagon/epinephrine → PKA; insulin → Akt, PP1
* Keep an eye out for isozymes (different versions of enzymes) that are present in different tissues and/or compartments and have different properties with regards to activity &/or regulation
* “Logical types” of enzymatic regulation - Recognize examples of:
* Feedback inhibition (prevent backup when enzymes down the line can’t keep up)
* Feedforward stimulation (prepare enzymes down the line for what’s coming)
* Crosstalk between pathways
more on all sorts of metabolic stuff: bit.ly/bbmetabolism

[@scfrhc9131]

I find your subject treatment fascinating and enlightening. After considering the presented metabolic pathways I was actually wondering if you were aware of whether there was a known pathway for the regulation of DNA methylation repair…it is my understanding that this repair mechanism differs between individuals. Some do it better than others accounting for the difference in predisposition to breakdown interference metabolism generally or for example oncology development specifically. Any thoughts or direction for study? Thanks for your great work!

[@thebumblingbiochemist]

Thanks so much! I'm not quite sure what you're referring to, but there is lots of ongoing work on methylation and its modification