Cell Language Theory, The: Connecting Mind And Matter

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“6x9” b2861 The Cell Language Theory: Connecting Mind and Matter

In contrast, PFH would suggest the following alternative mechanism:

R + R + H ↔ R•R + H ↔ R•H•R → biological actions. (3.16)

In other words, PFH predicts that receptors can (and indeed must)

dimerize before hormones can bind, again for the same kinetic reason as

indicated above: The thermal motions of R’s are so slow relative to the

speed of collisions between H and R under physiological conditions that,

unless R’s are already brought close enough to each other via Brownian

motions, H could not be “captured” by R before it bounces back from the

binding pocket of R into the surrounding medium.

The X-ray crystallographic investigations on erythropoietin receptor

(EpoR) provide another evidence for PFH. EpoR is the receptor for EPO,

a glycoprotein (i.e., a protein covalently linked to sugar residues) that,

upon binding to EpoR, regulates the proliferation, differentiation, and

maturation of red blood cells. EPOR was thought to be activated by EPO-

induced dimerization, but the X-ray structural data on the extracellular

domains of EpoR, known as the EPO binding protein (EBP), have indi-

cated that EpoR can form a dimer in the absence of EPO [76], in agree-

ment with PFH, i.e., Process (3.16).

3.2.10 Allosterism, Bohr Effect, and Wyman’s Pseudolinkage

Allosterism refers to the phenomenon of the interaction between two sites

within a biopolymer complex. For example, in the Bohr effect [168], when

the oxygen molecule binds to the heme iron of, say, the a-subunit of the

tetrameric hemoglobin molecule (consisting of two units each of the a and

b chains denoted as a 1 , a 2 , b 1 , and b 2 ) (Figure 3.16), the heme iron and the

5th ligand histidine move into the heme plane by 0.6 Å. This causes an

amplified displacement of atomic positions in the a 1 b 2 interface by up to

6 Å, resulting in an increase in the acidity (or a decrease in the pKa value)

of certain amino acid residues located 5–10 Å away from the heme center

so that one proton is released for every two oxygen molecules bound to

hemoglobin. The reciprocal coupling between the oxygen binding to and

proton release from hemoglobin allows the hemoglobin molecule to

deliver oxygen from the lung to tissues where it is needed and transport

CO 2 from tissue to the lung where it can be expelled, thus making

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