The Humble Phosphate Ion: Making Life “Go”

Author: John Charpentier

Editors; Noah Steinfeld, Tricia Garay, and Scott Barolo

A glance into any organic chemistry or biochemistry textbook reveals a dizzying variety of chemical compounds, reactions and mechanisms. It is not at all obvious why one particular class of reaction, the attachment and detachment of a phosphate group (PO43-) to molecules like nucleotides and proteins, is central to making the chemistry of life “go.”

Proteins: Not Just for Getting Swole, Brah

Fig1
Figure 1. A phosphate ion. Note the negative charges.

Proteins are the working-class heroes of the cell: they get things done. A protein’s function is largely determined by its shape, which in turn is dictated by the linear sequence of chemically distinct amino acid subunits it is composed of. The rules of protein folding are astonishingly complex. Generally speaking, the reluctance of hydrophobic (“water-fearing”) amino acids to project outward into the watery cytoplasm is the primary determinant of protein shape, but electrostatic interactions between amino acid residues are also important. Phosphate groups have three negative charges, which means that when they are linked to or removed from a protein by specialized enzymes, they can dramatically modify its shape and stability, and therefore its function. The phosphorylation/dephosphorylation cycle operates like a switch to regulate protein behavior: add a phosphate and you get a violent Mr. Hyde protein; take it off and you get the amiable Dr. Jekyll.

 

Fig2
Figure 2. Cellular homunculi don’t exist – decisions are made by integrating signaling inputs from the environment to effect changes in gene expression.

So where do we find phosphorylation in biochemistry? The answer is: pretty much everywhere! I will discuss two key examples. Firstly, phosphorylation is important in “cell signaling,” the sensing of messages from outside a cell and their incorporation into cellular decision-making. It’s worth observing that there isn’t anything we’d recognize as a brain in cells – decision-making is an emergent property of the integration of these signals, not the doing of a microscopic cellular homunculus pulling levers or “thinking.”

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Placebos: Tricking the Brain, Targeting the Body

Author: Shweta Ramdas
Editors: Charles Lu, Whit Froehlich, and Scott Barolo

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Placebo or Nocebo?

Last year, when I pooh-poohed my mother’s alternative medicine regimen, she said, “But these actually work well for me, because I believe in them!” My mother had just outsmarted me with science.

The placebo effect is one of the most remarkable yet least understood phenomena in science. It is a favorable response of our body to a medically neutral treatment (sugar pills, anybody?): in other words, a placebo is a fake treatment that produces a very real response. This is attributed to a physical reaction stemming from a psychological response to the administration of therapy. You could say that a patient sometimes gets better anyway—how many times have we waited out the common cold—and you would be right. This natural return to the baseline which can happen is not considered the placebo effect, which is an improvement in response to a treatment.

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