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Course: MCAT > Unit 2

Lesson 1: Foundation 1: Biomolecules

Enzyme kinetics: NTKase and NTKase deficiency


NTKA is a newly discovered (pretend) 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. Interestingly, NTKAse and NTKAse do not appear to have different rates of catalysis at saturating substrate concentrations (or different “kcat” values).
Researchers performed the following analyses to further characterize NTKA deficiency and NTKAse.
Experiment 1
Researchers isolated a large quantity of NTKAse protein from three different patients with a family history of NTKA deficiency. Patients 1 and 2 are of unknown genotype, while Patient 3 is homozygous recessive. Figure 1 shows a Lineweaver-Burke plot of NTKAse activity for each patient. The NTKAse activity of Patient 3 was measured in the presence of a drug known to limit the activity of NTKAse.
Figure 1 A Lineweaver-Burke analysis of NTKAse activity in Patients 1, 2, and 3
Experiment 2
Researchers cloned the gene encoding NTKAse (WT-NTKAse) and constructed several NTKAse variants. The dissociation constants (Kd) of NTKA for each of the NTKAse variants were determined (Table 1).
Table 1 Dissociation constants (Kd) of NTKA for Various NTKAse variants
NTKA is released into the synaptic cleft, where it’s eventually degraded by NTKAse. Compared with most patients, how would the signaling activity of NTKA change at the postsynaptic neuron in a patient with two copies of NTKAse?
Choose 1 answer: