- Hi everyone, my name is Charu,
and I'm excited to walk through an MCAT biochem passage
with you today.
As we go through the passage,
I'll share a few tips on how to approach science passages,
as well as strategies and how to tackle questions like these
on the MCAT
Alright, so we have the passage here in front of us,
and one of the first things that you'll notice
is that this is on the shorter side for an MCAT passage.
I'll be going through the passage at a slower pace
than what you should be doing on test day
just to ensure that we're able to review it in detail.
So let's get started.
The passage starts out with a figure
depicting a mouse antibody and a human antibody
with a heavy chain, light chain,
and highly variable regions color-coded.
The passage then reads,
researchers inject mice as an antigen
to induce the production of specific antibodies.
Upon confirmation of antibody production,
antibodies are isolated from the blood samples taken
from the mice and tested to determine if they are specific
to the antigen using enzyme linked (indistinct)
Researchers also conjugate drugs to antibodies
to produce drug conjugates called Nanobodies.
The Nanobodies localized to antigens
and often have a cleavable linker
between the Nanobody and the drug.
With an intention to localize Nanobodies
to the peripheral membrane protein.
Once an antibody localizes,
it can enter the cell through endocytosis
and then can be cleaved in a peroxisomes or lysosomes.
Upon cleavage the drug of payload is released.
So I'd like to pause here and point out a few things.
The first is a strategy that I like to use
which is to categorize sentences
or parts of the passage in my mind.
So I'd ask myself, does this particular sentence
or section provide an introduction to a topic,
an explanation of experimental design,
Are they describing their results
or some application of certain experiments?
Generally passages will start out
with some sort of introduction.
Here we noticed that they dive immediately
into the design of an experiment.
Another strategy I like to use is to contextualize situation
by paying close attention to where in the human body
or where in the cell the scenario
or experiment is taking place.
The passage tells us that Nanobodies localized to antigens
with the intention to localize
to a peripheral membrane protein.
The Nanobodies then enter the cell through endocytosis
and once they're inside the cell,
they're cleaved in peroxisomes or lysosomes,
and the drug is released.
The passage then goes on to tell us
the toxic drugs can be localized to cancer cells
without causing undue damage to neighboring cells.
So in my mind I would categorize the sentence
as an application of the information
that they just provided us with.
They're sharing with us how one could use this technique
to target cancer cells.
The passage then goes on to tell us that
in the follow-up experiment,
a Nanobody identified as N 96 successfully binds to HER2
an epidermal growth factor, highly expressed
in some breast cancers.
Scientists have a say that pH dependency
of affinity for HER2.
So, one thing I'd like to point out here
is that often on the MCAT,
passages will introduce new terms or new names
such as the names of receptors or proteins or cell lines
or something else.
These names can be complicated and may look unfamiliar.
My advice would be not to get overwhelmed
when you see names or terms that are unfamiliar.
But try to recognize the underlying concept
that they're testing you on.
In this case, they tell us that N 96 is a Nanobody
which is a drug conjugated to an antibody.
HER2 is an epidermal growth factor
highly expressed in some breast cancers.
While you may not have heard of N 96 or HER2 before,
you likely have learned about antibodies and growth factors.
Recognizing these underlying topics
that you're already familiar with,
can help to reduce your own stress levels
and anxiety during the exam.
Next, the passage provides us with another figure.
Normally what I like to do is to glance over a figure
and get a general sense of what it means.
And then if a question asks for more specifics,
I'll go back and look at it in more detail.
In this case, the figure is pretty straightforward
and shows us the pH dependency of N 96 is affinity for HER2.
You'll notice also that the binding percentage increases
around a pH of six, which is a maximum around a pH of eight
and then decreases as pH increases further.
So let's take a look at the questions.
The first question asks us,
which is a following is likely to be found
in human antibodies, but not mouse Nanobodies?
So if we go back to the passage,
we see that it's really in figure one
that we're provided with more information
to compare the structures of human and mouse antibodies.
We see that mouse antibodies
are composed of a single protein domain,
and these single units have to be functional on their own.
So we can assume that they wouldn't require
any sort of quaternary structure.
On the other hand,
both mouse antibodies and human antibodies
would need to have
some sort of antigens specific variable regions
as we can see shown in the figure.
They would both also likely have
some amount of hydrophobic residues,
and hydrogen bonding would likely contribute
to some sort of secondary or tertiary structure.
So this leaves us the answer choice C quaternary structure
as the correct answer choice.
And then question two asks us,
researchers hope to identify the antigen binding region
of the Nanobody.
Based on information provided in figure two,
which of the following amino acids is most likely
in this region?
So the question tells us that we should be focusing
on figure two.
And in figure two we can see
that binding peaks around a pH of eight,
it gradually decreases as you go above a pH of eight
and pretty decreases as you move
below a pH of seven or eight.
This rapid decrease is likely due to the protonation
of some residue.
One tip for the MCAT
is to be very familiar with amino acids.
So knowing their structures, their abbreviations,
knowing which amino acids are polar or non-polar,
acidic or basic.
Out of the answer choices,
histidine has a PKA of around six,
which is consistent with the information we're given
in figure two.
Arginine and lysine on the other hand are basic
and we'll have a higher PKA.
Aspartic is acidic and we'll have a much lower PKA value.
So this leaves us with answer choice A
as the correct answer.
And then question three asks us about
which of the following residues is most likely to be found
on the outside of N 96?
This question also requires us to rely on our knowledge
of that amino acids.
Phenylalanine, leucine and valine
are all non-polar amino acids
which are much more frequently found
on the interior proteins.
In comparison threonine is a polar residue
with a hydroxyl group,
so it's more likely to be found on the outside of N 96.
And then question four says,
during drug delivery the Nanobody linker is cleaved
by an intracellular protease
which recognizes this particular pattern
or X is any non-polar amino acid residue.
Which of the following amino acids
should not be included in the linker?
Based on the question stem
we know we're looking for an amino acid that is non-polar.
Isoleucine, valine, and phenylalanine
are non-polar residues.
And thus could not be used in the linker.
Or sorry thus could be used in the linker.
Glutamine however, is a polar amino acid
and could not occupy the expositions.
And for that reason is the correct answer choice
to this question.
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