u/Inner_Paramedic313

▲ 2 r/Mcat

Not-So-Deep Dive: Mesolimbic Pathway

NOT the addiction version of Limbic Pathway as I had thought of it for a very long time before a question humbled me 😛 so I thought I might share

Think of Limbic Pathway is terms of structure: HIPPO HAT

  • Hippocampus: long term memory (review LTP, NMDA, etc)
  • Hypothalamus: hormonal mastermind (review hormonal axises, 4 Fs)
  • Amygdala: primary emotions for survival (not just anger)
  • Thalamus: sensory information sorter (review LGN, MGN, NOT olfactory tho. That goes from bulb straight to amygdala + hippocampus which is why we have IMMEDIATE emotional responses to smell, I always think of ratatoullie haha)

Think of Mesolimbic pathway as use of these structures that could result in addiction ( major simplification).

I used these two 'mnemonics', yeah it helped with 'order' but it really solidified my understanding of function and I didn't have to learn it separately and I can still recall it perfectly to this day.

Very Nasty Addictive Habits Persist

Produce → Reward → Feel → Remember → Decide

Ventral Tegmental Area (VTA) (midbrain)

  • produces dopamine & initiates reward signaling

Nucleus Accumbens (forebrain)

  • receives dopamine
  • reinforces rewarding behavior: that was rewarding, repeat it!

Amygdala (limbic system)

  • emotional significance, emotional attention seeking: how did it feel, emotionally memorable?

Hippocampus (limbic system)

  • contextual + episodic memory: remember this reward and context

Prefrontal Cortex

  • planning, decision making, impulse control, motivation integration: plotting on getting the stimulus again, when, how, how often, etc.

Hope it helps even one person! We got this!!!

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u/Inner_Paramedic313 — 3 days ago
▲ 7 r/Mcat

Review Deep Dive: Km vs Kd

Hi, as my MCAT is approaching, Im doing some final deep dive reviews and thought I might share bc I care. This is gonna be some 'low yield' convoluted stuff but here we go:

First understand how Michaelis-Menten graphs are made. It is not following one rxn over time. Several reactions are conducted with only changes to [substrate] and the rxn Vo is mapped for the final graph (seems intuitive but its easy to overlook). This is why its inherently a tool for indicating kinetic parameters of a rxn.

Vmax: They keep increasing [S] till Vo hits a plateau - thats Vmax.

Km: [S] at half the Vmax - measure of ES 'affinity' (↑Km = ↓affinity)

kcat: Turnover number (or product formation rate): Vmax/[Enzyme]. Intuitive reason why only [E] can change Vmax.

kcat/km: Catalytic efficiency (take a sec to think about why its inverse of Km).

Now I've seen people confuse Km with Kd bc they both are about 'E & S affinity' but its not the same.

We can have 3 rxn rates overall:

Forward k1: E + S → ES. Ka= k1/k-1

Backwards k-1: ES → E + S. Kd=k-1/k1

Product formation kcat: ES → E + P

These are 'intrinsic' thermodynamic properties of the enzyme substrate binding affinity at equilibrium (assuming all other parameters like T, pH, etc are kept same while determining this value). They are answering if we preferentially see more ES or free E + S at equilibrium.

(Note: k1, k-1, kcat are kinetic properties but Ka and Kd are thermodynamic.)

Kd CAN approximate Km however if kcat (product formation) is VERY slow relative to K-1 (disassociation).

Km reflects the overall stability/effectiveness of the ES complex (think back to why uncompetitive inhibition = ↓Km/'↑affinity'). Again, Km is kinetic, not purely equilibrium based bc ES can disappear by TWO pathways: dissociation back to E + S OR product formation.

So Km= k-1 + kcat/k1 (similar to product/reactant concept bc we can lose amount of ES(reactant) through either ES → E + S or ES → E + P (both rates are 'products' bc they deplete reactant)).

In case of very low kcat, ES → E + P is barely happening, the ES complex is associating & disassociating back and forth instead of making a product. The system behaves almost like a 2-rate reversible binding equilibrium with k1 and k-1. So Km~k1/k-1 which is the same as Kd.

If you wanna tackle it conceptually, Km is about ES 'strength' right? If we ignore kcat (approximate a 2 rate constant system) would Ka tell you ES strength or Kd? Ka would only tell us ES is forming, it wont tell us if ES is persisting/not falling apart which is better indicated by Kd, the dissociation constant. Like Km, ↑Kd = ↓affinity.

>!Inspired by FL5 CP Passage 1!<

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u/Inner_Paramedic313 — 9 days ago
▲ 1 r/Mcat

Begging for help with OChem

Chemistry was the bane of my existence, I got through it in school with pure memorization and pattern recognition (grades weren't great but I got though) and now its biting me in the tush.

While studying for MCAT I got much better with gen-chem stuff (thermodynamics, redox, gas laws etc) but I'm hitting a block with Ochem. For example, FL4 CP Q30-33 where all guesses from me. I'm good with structure/names so thats what my guesses are based on but I'm loosing it tbh.

I've tried to reteach it to myself countless times but I'm too lost in the sauce yall. This is what happens: I'm confused about x so I go watch a video, to understand x it seems like I should understand y first but to understand that I should understand z first and it keeps on going till the cows come.

If anyone would has any resource/advise or time to walk through a couple practice questions with me, I'm begging. Ik theres not much of it on the MCAT but I need all the help I can get, I'm only a couple points below my goal score 😞

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u/Inner_Paramedic313 — 12 days ago