Proton release, extracellular side

The apparent symmetry of proton uptake and release on either side of the purple membrane suggests that proton release at the extracellular side and its reverse reaction may be manifest as a displacement photocurrent (a hypothetical B2 component). This signal is blocked in a Trissl-Montal bacteriorhodopsin film because the Teflon film precludes access of aqueous protons at the extracellular side. If, however, bacteriorhodopsin is reconstituted in a lipid bilayer membrane, this hypothetical component, which represents proton release at the extracellular side, might be observable. A complication arises from the expected polarity of the B2 signal, which should be the same as that of the B2 component (both are of opposite polarity to the B1 component). Therefore, a method must be devised to distinguish the B2 from the B2 component. The following kinetic analysis provides the rationale for such a method. 

Fig. 8. Tentative scheme of the mechanism of the catalytic activity of bacteriorhodopsin. indicates that reprotonation during the photocyde of bacteriorhodopsin occurs from the cytoplasmic side. A proton is released first at the extracellular side of the membrane.

As pointed out already, proton transfer in bR is activated by photoisomerization of all the tran -retinal to the 13-cis form, followed by proton transfer from the retinal Schiff base to Asp 85, release of a proton from residues or water molecule(s) at the extracellular surface, and uptake from the cytoplasmic surface through reprotonation of the Schiff base by Asp 96. This results in a proton transfer from the cytoplasmic to the extracellular side. It appears that this process proceeds with induced conformation and/or dynamic changes at both the extracellular and cytoplasmic side owing to protonation of Asp 85. This means that the information of the protonation at Asp 85 should be transmitted to both the extracelluar and the cytoplasmic regions, through specific side-chains or through backbone interactions. 

The NADPH binding site is on the cytosolic side of the membrane, whereas the superoxide release site is either extracellular or on the luminal side of the phagocytic vesicle. The enzyme acts as an ion pump, because it releases superoxide without an accompanying cation protons remain inside the cell, resulting in considerable membrane depolarization (Babior, 1992 Chanock etal., 1994). 

Bicarbonate and carbonic acid, which diffuse through the capillary wall from the blood into interstitial fluid, provide a major buffer for both plasma and interstitial fluid. However, blood differs from interstitial fluid in that the blood contains a high content of extracellular proteins, such as albumin, which contribute to its buffering capacity through amino acid side chains that are able to accept and release protons. The protein content of interstitial fluid is too low to serve as an effective buffer. 

Serotonin, also known as 5-hydroxytryptamine (5-HT) is biosynthesized from tryptophan and is a neurotransmitter. Serotonin plays an important role in many behaviors including sleep, appetite, memory, and mood [52]. People with depressive disorders exhibit low levels of serotonin in the synapses. Protonated serotonin binds to a serotonin reuptake transporter protein, sometimes referred to as the serotonin transporter (SERT) and is then moved to an inward position on the neuron and subsequently released into the cjdoplasm. Selective serotonin reuptake inhibitors (SSRI) bind with high affinity to the serotonin binding site of the transporter. This leads to antidepressant effects by increasing extracellular serotonin levels which in turn enhances serotonin neurotransmission [53]. The SSRI class of antidepressants has fewer side effects than the monoamine oxidase inhibitors. 

---