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MCAT

Unit 2: Lesson 1

Foundation 1: Biomolecules

Biochemistry of a newly discovered (pretend) neurotransmitter

Problem

NTKA is a newly discovered excitatory neurotransmitter. After its release into the synaptic cleft, NTKA is cleaved into two components, NT and KA, by an enzyme known as NTKAse.
A new disease, with an autosomal recessive mode of inheritance, is characterized by NTKA deficiency. Autosomal recessive NTKA deficiency is caused by a hyperactive NTKAse enzyme, “NTKAse,” which binds NTKA with a much higher affinity than wild-type NTKAse, quickening the depletion of NTKA from the synaptic cleft. Interestingly, NTKAse and NTKAse do not appear to have different rates of catalysis at saturating substrate, “start text, k, end text, start subscript, c, a, t, end subscript”.
Three patients volunteer for a study involving NTKA deficiency. Via in vitro genetic manipulation, researchers are able to produce a large quantity of NTKAse protein from each of these patients and characterize them biochemically. Figure 1 shows a Lineweaver-Burke plot of NTKAse activity for three patients, each of whom has one or more relatives with NTKA deficiency. Patients 1 and 2 are of unknown genotype, while patient 3 is homozygous recessive. The NTKAse activity of Patient 3 was measured in the presence of a drug known to limit the activity of NTKAse.
A Lineweaver-Burke plot can be used to characterize an enzyme’s activity in different concentrations of substrate. The reciprocal of the enzyme’s rate of reaction, 1, slash, V, is plotted against the reciprocal of the substrate concentration, 1, slash, open bracketSclose bracket. The enzyme’s maximum rate of reaction, start text, V, end text, start subscript, m, a, x, end subscript, and the enzyme’s binding affinity for substrate, start text, K, end text, start subscript, M, end subscript, can be extracted from the plot’s y- and x-intercepts, respectively. A low start text, K, end text, start subscript, M, end subscript indicates high binding affinity, whereas a high start text, K, end text, start subscript, M, end subscript indicates low binding affinity.
Figure 1: A Lineweaver-Burke plot was used to characterize the start text, V, end text, start subscript, m, a, x, end subscript and start text, K, end text, start subscript, M, end subscript values of NTKAse in three patients.
How would the signaling activity of NTKA change at the post-synaptic neuron if a molecule that specifically bound the NTKAse active site were added to the synaptic cleft?
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