The Ultimate Recycler

a power grid reaches straight up to a blue sky. Demand for power is high how do we meet our own demand for power?
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When a city starts out with a major energy deficit, there are two changes that should be made: to be really, and I mean really efficient at recycling the critical resource, or to buy more energy.

What about in biology? Cells are like cities, right?

We already know from the previous post that the cell has an energy budget that is out of balance based solely on biosynthesis and use of AT.P It is in a predicament. It has an extreme shortfall in ATP in its balance sheet, needing six ATP just to make one. ATP is a high energy molecule. All that energy has to be loaded into the molecule during its synthesis by using up other ATP molecules.

The chemical structure of ATP shows three high energy phosphate bonds.

If chemical A is necessary for the synthesis of more chemical A, then A has the power of replication (such systems are known as autocatalytic systems). …We find that intermediary metabolism is invariably autocatalytic for ATP.

Kun et al., Genome Biology 2008, 9:R51

The cell needs to have ATP before it can make ATP, and it has to have more ATP than it can make. Can the cell rescue its metabolic state by bringing in ATP from outside? Sure, indirectly– if it eats biological material other cells have made, it can get ATP by breaking down glucose into pyruvate, and then pyruvate into citrate, and then ultimately, the energy is harvested and and a net gain in ATP is produced. The glucose to pyruvate digestion happens in the cytoplasm, but the citrate to final energy harvest all occurs in marvellous mysterious voyagers in our cells called mitochondria.

Mitochondria are the microscopic power plants of the cell whose purpose is to take citrate and convert it to ATP,

the cell’s energy currency. Resembling miniature blimps with corrugated double membranes, they carry out an interlocking series of chemical reactions that squeeze out every last possible ATP from the breakdown of glucose. It’s a highly efficient, environmentally friendly process.  Everything is recycled — one part of the process is called the citric acid cycle because it regenerates itself with each new round. In fact, everything cycles.

Most cells have many mitochondria, whose characteristic wrinkled stroma serve to increase the interior membrane surface area. Think of a bag with a much bigger bag neatly tucked in folds inside. Embedded in that folded inner membrane are all machinery of energy production that makes life possible. And that machinery is considerable. An ensemble of multiple proteins come together to make 5 protein complexes, shown in the picture below. In complexes 1-4, energy in the form of electrons is received by them and cycled through and, then using some of that energy to pump protons across the membrane. As citrate is gradually broken down, compounds like NADH or succinate are produced, and shunted off to the electron transport chain, and they also contribute to the process.

Even the last high-energy electrons from the breakdown process are not wasted: a chain of proteins in the inner membrane passes these electrons like little hot potatoes from one to another, using the energy of each transfer to pump hydrogen ions across the membrane, so that a molecular machine called ATP synthase can take advantage of the hydrogen gradient to create even more ATP.  

The protein structures of the electron transport chain of the mitochondrion. These complex structures harvest energy and pump protons so that AdP can be recycled back to ATP.
The protein complexes of the mitochondrial electron transport chain, showing the flow of molecules in and out of the mitochondrion at each stage. doi:

In the drawing you can see the direction of H+ flow out and then in again, and how many different proteins make up each protein complex. There are 5 complexes, whether in an animal, or a plant.

The fifth complex is ATP synthase. This is where the miracle happens that makes life possible. ATP synthase harvests the energy of the proton gradient to recycle ADP to ATP. Like a turbine in a hydroelectric plant, ATP synthase lets the hydrogen ions flow back across the membrane through itself, rotating as the ions pass through, and As it rotates it adds a phosphate to ADP at each crank, thus restoring ATP to use.

ATP synthase is the name of the protein complex that performs the ADP to ATP conversion. A video is listed that describes its action.

The engine ATP synthase is 98% efficient at what it does! Human machines can’t approach that. But this is what permits life. We burn through our body weight in ATP every day. Just breathing burns ATP.

Right now, within your bodies this little engine is cranking away. Without this machine, oxygen-dependent life could not exist. Strong statement, but I stand by it.

To put it all together, in all life’s glorious improbability and elegant design, will require another post. And I haven’t even gotten past the beginnings of biochemistry.

For a video: ATP Synthase: The power plant of the cell

The Hidden City

Hong Kong Street at night UCLARodent at English Wikipedia [CC BY-SA 2.5 (

Picture a hidden city, that though it cannot be seen, is everywhere. Sound crazy? It’s real. And it is the most antic, madcap, crowded yet fantastically efficient city you could ever picture. It’s like Hong Kong sped up to an almost unimaginably manic pace, with all kinds of independent, apparently purposeful activities going on — fast, fast, fast! — conducted by a huge cast of actors (enzymes and other intricately sophisticated molecular machines made of proteins) that go about their business as if it were their business. There, I gave it away. This mysterious city I write about is a microscopic cell, made of DNA, RNA, proteins, and membrane. No doubt you were taught to think of a cell more or less statically, but it is a highly dynamic ever changing entity. How is all this activity coordinated and directed? The answer remains largely mysterious, and the more we find out the more the mystery grows.

We do know this much. The nucleus is where DNA, the cell’s information storage system, resides. It serves as the cell’s Grand Central Library, where a good deal of the coordination takes place. DNA, the chief orchestrator, looks like a tangled mess, but it isn’t, it’s quite organized. It has to be. Supercoiled DNA packs tightly against the nuclear wall, inactive. Nearer the center, active chromosomes stake out territories, so that in the center, their unwound loops of DNA can partner with others in an intricate dance. Clouds of signal molecules surround these loops, looking for binding sites near genes. Most genes have multiple binding sites near them. When occupied, the binding sites send signals— yes, no, no, yes, yes   — that get integrated into one overall signal. When it adds up to yes! a cascade of events begins — another kind of binding protein sits down on the DNA like a rider in a saddle, right in front of the gene, and attracts other proteins to itself, one by one. Then the cluster attracts a wandering machine called an RNA polymerase, which will copy (transcribe) the DNA into RNA. The whole complex waits like a race horse in the starting gate until the signal is given, then bang! the polymerase whizzes off, transcribing DNA into RNA at an astonishing clip of 30 nucleotides per second.

Sometimes the polymerase jumps between strands, forming an RNA made from two separate chromosomes. Sometimes polymerases racing in opposite directions run into each other, like Keystone cops. And sometimes polymerases run into what are called replication forks, the places where DNA is being duplicated in order for the cell to divide. The RNA polymerase politely steps aside.

You are probably wondering what the RNA is good for.  It gets processed and shipped out to the cytoplasm, where it is turned into proteins like the polymerase and binding proteins, or the thousands of other proteins the cell requires. Proteins are the actors that accomplish things in the cell, and the building blocks from which things are made. You will meet other examples as we go.

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