Synapse Biochemistry - Biochemistry

Tyrosine hydroxylase is the rate-limiting enzyme for catecholamine synthesis. It catalyzes the conversion of tyrosine to dihydroxy-phenylalanine (DOPA). Tryptophan hydroxylase is the rate-limiting step for serotonin synthesis. Dopamine beta-hydroxylase converts dopamine to norepinephrine. Amino acid decarboxylase converted DOPA to dopamine.

Chromaffin cells are located in the adrenal gland, and release epinephrine and norepinephrin.

Chromaffin cells release both epinephrine and norepinephrine, but 80% of the neurotransmitters released is epinephrine.

Of the options given, only norepinephrine is synthesized in storage vesicles. The rest are synthesized in cytoplasm.

Dihydroxyphenylalanine (DOPA) is the precursor for dopamine. Of the options, only dopamine, epinephrine, and norepinephrine are released upon nerve firing.

Tyrosine hydroxylase is the rate-limiting enzyme for all catecholamine synthesis reactions. L-aromatic amino acid decarboxylase is needed to catalyze the step from DOPA to dopamine. Norepinephrine synthesis requires dopamine beta-hydroxylase and epinephrine synthesis requires dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase (PNMT) in addition to the other enzymes mentioned.

NETs are used to remove norepinephrine from the synaptic cleft. Tryptophan hydroxylase and amino acid decarboxylase are part of the serotonin synthesis pathway. VMA is a breakdown product of norepinephrine.

Parkinson disease is associated with decreased dopamine concentration. It is commonly treated with L-DOPA, which can cross the blood brain barrier and be converted to dopamine.

Tryptophan is the original substrate for serotonin synthesis. All other answers are involved in the catecholamine synthesis pathway.

Tryptophan hydroxylase is the rate-limiting step of serotonin synthesis, not to be confused with tyrosine hydroxylase.

Monoamine oxidase (MAO) is responsible for inactivating catecholamines and serotonin. Thus, inhibiting MAO would result in an increase of catecholamines and serotonin.

Of the options, only COMT is involved with catecholamine and serotonin breakdown. The rest are enzymes in the catecholamine synthesis pathway.

Epinephrine binds to the alpha-adrenergic receptors of the beta cells. Via intracellular signaling cascades beginning with the G protein-coupled receptor, adenylyl cyclase is activated, converting ATP to cAMP. Epinephrine is released from the adrenal medulla, not the adrenal cortex. It is also elevated when insulin is low, not high.

The release of calcium ions at the axon terminal is responsible for the exocytosis of vesicles carrying neurotransmitters.

When an action potential reaches the synapse, choline enters the neuron. Once inside, the choline molecule binds to acetyl-CoA and forms acetylcholine, which is then packaged into vesicles. Upon calcium influx, the acetylcholine vesicles fuse with the synaptic membrane and release acetylcholine into the synaptic cleft. The acetylcholine molecules can now bind to receptors on the postsynaptic membrane and initiate an action potential in the postsynaptic neuron.

Acetylcholine is a neurotransmitter found in neuromuscular junctions. Release of acetylcholine into the synaptic cleft allows acetylcholine to bind to its receptors on the muscle membrane. Once bound, acetylcholine activates a signaling cascade that eventually leads to muscle contraction. Circulating antibodies in Myasthenia gravis patients prevent this interaction between acetylcholine and its receptor, thus decreasing muscle contraction. One way to treat this disease is by administering drugs that increase the half-life of each acetylcholine molecule. The most common way to do this is by administering an acetylcholinesterase inhibitor. Acetylcholinesterase is an enzyme that breaks down acetylcholine molecules in the synaptic cleft; decreasing or inhibiting this enzyme will lead to increased acetylcholine concentration. This increased concentration will compete with the antibodies and facilitate muscle contraction. Decreasing calcium influx in the presynaptic neuron will decrease the release of acetylcholine into the synaptic cleft. This will make Myasthenia gravis symptoms worse.

There are two types of synapses: electrical and chemical. Electrical synapses have gap junctions between adjacent cells and are usually found between cardiac muscle cells. Chemical synapses are more abundant and utilize neurotransmitters (such as acetylcholine) to transmit signals between adjacent cells. They are typically found in neuromuscular junctions of skeletal muscle cells.

Transferases are not neurotransmitters and can be omitted from selection. Catecholamines and small-molecule transmitters are overlapping categories and are typically packed in small, clear core vesicles. Gasotransmitters are membrane permeable and do not require vesicles for release. Neuropeptides are unique in that they are large and are synthesized at the ER, and are packed in large, dense vesicles, and thus this is the correct answer.

An influx of calcium at the presynaptic terminal is absolutely required to activate fusion of vesicles with the membrane, and therefore release of their contents into the presynaptic cleft. Given that the specific deficit in these mutants is at the final stage of fusion, we know that the action potential propagated (so it's likely not sodium or potassium) and the presynaptic membrane is not responding to the voltage change to permit an influx of calcium. Therefore, voltage-gated calcium channels are the likely cause of this deficit.