Your Copper Pipes
Each of us is part metal. Our bodies contain iron, copper, zinc, magnesium, manganese, vanadium, molybdenum, selenium, and even nickel like the coins in our pockets or purses. Unlike the other common elements of life (carbon, oxygen, hydrogen, calcium, nitrogen, phosphorus), our metals are not synthesized and recycled, but must be imported and handled with care. Copper is a good example of a biological metal that performs multiple useful functions – that is, unless something goes wrong with the machinery handling it.
Richard A. Festa and Dennis J. Thiele (Duke University of Medicine) began an article in Current Biology explaining why biological metals are fascinating:1
Life on Earth has evolved within a complex mixture of organic and inorganic compounds. While organic molecules such as amino acids, carbohydrates and nucleotides form the backbone of proteins and genetic material, these fundamental components of macromolecules are enzymatically synthesized and ultimately degraded. Inorganic elements, such as copper (Cu), iron and zinc, once solubilized from the Earth’s crust, are neither created nor destroyed and therefore their homeostatic regulation is under strict control. In the fascinating field of ‘metals in biology’, by virtue of direct interactions with amino acid side-chains within polypeptide chains, metals play unique and critical roles in biology, promoting structures and chemistries that would not otherwise be available to proteins alone.
Because copper can exist in an reduced state (Cu+) and an oxidized state (Cu2+), it is a candidate for versatile functions – as indeed it is employed in all living things. But copper is also a potential toxin: “free intracellular Cu can generate hydroxyl radicals, which can damage proteins, nucleic acids, and lipids, and can interfere with the synthesis of iron–sulfur clusters that are essential for the activity of a number of important cellular enzymes.” It must, therefore, be handled with care. Here is a short list of machines that handle this useful but risky metal:
- Importers, exporters and transporters: enzymes that catch copper and take it inside or outside the cell or to organelles.
- Transcriptional repressors: cofactors that provide copper homeostasis under low Cu conditions by repressing genes that would otherwise export copper.
- Metalloreductases: enzymes that reduce Cu2+ to Cu+.
- Chaperones: enzymes that help assemble metalloproteins containing copper, or get copper ions across the placenta membrane or the blood-brain barrier.
- Energy pumps: cytochrome c oxidase (part of the electron transport chain in oxidative phosphorylation) is found in prokaryotes and eukaryotes; NADH dehydrogenase 2 is another component of the chain in eukaryotes.
For an example of the complexity of these machines and their functions, here is an excerpt from the paper:
Metazoans not only need to acquire Cu and mediate its intracellular distribution, they must also parse Cu out to peripheral tissues where it drives cellular processes, such as the high demand for mitochondrial oxidative phosphorylation in brain and heart tissue. In mammals, Cu transported across the apical membrane by Ctr1 in intestinal enterocytes is shuttled to the ATP7A Cu-transporting P-type ATPase at the basolateral membrane by the Atox1 Cu chaperone and pumped into the portal circulation, where it makes its way to the liver, the major Cu storage organ. ATP7A plays crucial roles in moving Cu across other polarized cell layers, including the placenta and the blood–brain barrier, to ensure adequate Cu in the developing fetus, and to meet the high demands for brain development and function. Similar to Ccc2 in yeast, ATP7A is also important for the delivery of copper to nascent proteins in the Golgi apparatus. In mammals, ATP7A is expressed in many tissues except the liver, where its expression is high in neonatal mice and diminishes during maturation…. How mammals sense tissue Cu deficiencies and elaborate signals that communicate with Cu acquisition and storage organs will be an important area for further investigation.
Festa and Thiele described how copper is used in everything from archaea, prokaryotes, fungi (yeast), plants, and mammals. With increasing complexity of the organism more machinery is found to handle copper (archaea, for instance, are mainly concerned with keeping it out). They inferred, therefore, that the machinery “evolved” over time from simple to complex as oxygen levels rose on the Earth.
Never once, though, did they explain how copper metalloproteins (or the genes that code for them) arose. Nor did they describe transitional forms from microbes to mammals; on the contrary, for example, “Several mitochondrial-associated proteins, including Cox17, Sco1 and Sco2, … are conserved from yeast to humans,” they said. Plants, surprisingly, have the most complex suite of copper proteins, “perhaps due to the presence of both mitochondria and chloroplasts, their relatively sessile lifestyle, and a collection of Cu-dependent proteins that are unique to plants.” The authors also noted that mutations to metalloproteins can be disastrous: failures in copper homeostasis have been linked to Wilson’s disease (a liver malfunction), Parkinson’s disease, Huntington’s disease, Menke’s disease, and Alzheimer’s disease.
So while the authors know that “Given that Cu is also a potentially dangerous toxin exploited by immune cells and that Cu dysregulation causes human disease, the homeostasis of this metal ion must be under exquisite regulatory control,” they did not and could not explain how the copper-handling machinery originated in the first place, despite their opening claim, “It will become clear that, as life evolved, more complex roles for Cu arose, concurrent with the elaboration of mechanisms to tightly regulate acquisition and distribution of Cu and provide protection against Cu toxicity.”
1. Copper: An essential metal in biology. Richard A. Festa, Dennis J. Thiele. Current Biology – 8 November 2011 (Vol. 21, Issue 21, pp. R877-R883).
Watching the Darwin mystics get away with miracles masquerading as science gets so aggravating, one could fill a bucket with warm spit. Watch them at this racket:
With the evolution of single-cell eukaryotes came the new challenge of deliverying [sic] Cu to an expanding array of metalloproteins located within organelles such as mitochondria, chloroplasts, and the secretory compartments.
A striking example of how Nature has evolved multiple uses for elements is the observation that, although Cu is essential for many biological processes, Cu is also a potent anti-microbial weapon against invading pathogens.
Given that eukaryotic cells have elaborate compartments and organelles in which Cu-dependent proteins reside or traverse on their journey to be secreted, tightly controlled intracellular Cu-delivery mechanisms have evolved.
Stop it! Aaagh! This is worse than fingernails scratching on a chalkboard. It’s perverse and pervasive. All across the world, scientists are scraping their fingernails on the chalkboard of intelligent design, calling it a Darwin symphony. These people make a horrendous racket with their racket.
But what about the clear observation that there is an increase in the number and complexity of copper-handling machines from archaea up through prokaryotes, to simple eukaryotes like yeast, and on up to metazoans, plants and mammals? Doesn’t that suggest evolution? Not at all. The scientific data can make no such determination. The same observations are amenable to a top-down interpretation, leading to the inference that the most complex came first in the design, with microscopic, tiny organisms, having no need for the higher functions, receiving stripped-down copper-processing machinery. Given the multiplied improbable miracles that would be required to produce even one metalloprotein by chance, the top-down view clearly is the more parsimonious, harmonious, and symphonious.