Elegant Bureaucracy: Biochem 101

Eliana & Jake per Orcianiby Sara Cimino

I often imagine the body as a factory: a collection of state-of-the-art machinery and skilled workers, optimized to produce thingies (let’s say jackets) at record speed. In this streamlined operation, regulation is critical for the maintenance of desired quality and quantity. Imagine: if you had just been handed the reins to such an efficient and productive enterprise, you'd probably want to make sure that things went more-or-less perfectly. Be warned, however, maintenance of such a system requires incredible oversight and as a manager you must cope with external or internal changes that threaten your jacket-production scheme. Regulation is indispensable in this factory: you will need to ensure that the tailors are supervised by higher-level supervisors, who are checked by managers, who are then checked by manager-checkers… Whew, it gets exhausting, and this is probably why biochemistry is so intimidating. It might not be immediately intuitive what 'checks' make sense, but understanding the basics of regulation should help you to better guess what reactions will likely ensue under a given condition.

Here are a few scenarios that might drive the basics home:

Scenario #1: Arnold finishes the hemming on the jackets and then passes them to Mickie, who is responsible for attaching the buttons. In the event that Arnold is working so quickly that there’s a huge buildup of jackets for Mickie to finish, does this motivate Mickie to work even harder or does he continue at the same pace? I hope you said he’d work harder. With the status quo being threatened, Mickie steps ups to restore things to normalcy, even if this means speeding up his own efforts or enlisting several other ‘Mickies’ to assist: this is an example of what we call Le Chatelier's principle, where a system responds to changes by re-adjusting to restore equilibrium. In biochemistry terms, the excess of one reactant will tend to drive the subsequent reaction (called the forward reaction) and an excess of product may slow down the forward reaction. For example, after eating a meal the absorbed carbohydrates will spike your blood sugar, which triggers insulin secretion; insulin works to bring glucose from the blood into the cells, thus lowering blood sugar. Now we are back to equilibrium.

In the first scenario, you had two people working consecutively to achieve the aim of producing jackets. The set-up could be different, however. You could, for example, have two specialists hired for performing perfectly opposite functions. Enter Scenario #2: On staff you’ve got Ruby, who is excellent at attaching little rubies to these couture silk jackets of yours, and De-ruby, who expertly removes the rubies.

I’m sure this raises a few questions... for example, why would you ever want to remove these rubies? Well, because on some occasions, there is a shortage of rubies in the market and rather than having them on your jackets you’d do better by releasing them back into the market. Or: why can’t Ruby be in charge of detaching them? Well, because she’s a specialist and her expertise is in attaching, not de-taching, rubies.

You've hired Ruby and De-ruby because each has an indispensable job function, but imagine how upset you'd be if you found out that they were both present at work and running full speed at the same time! Clearly it's a waste of money and energy to have these two antagonists on the job simultaneously. To ensure that energy is not being wasted on a process that will be quickly reversed, there must be reciprocal regulation or negative feedback. Ideally, Ruby and De-ruby would only work when the net aim is to make jackets with rubies or obtain individual rubies respectively. A great biological example of this is seen in the operation of insulin and glucagon, responsible for reducing and increasing serum glucose respectively. Insulin is secreted in order to neutralize the spike in blood glucose immediately after a meal (it does this by stimulating a range of pro-insulin processes); Glucagon secretion gets stimulated hours after a meal when the blood sugar has fallen (with the ultimate aim of producing glucose to be released into the blood).

By now, it should be clear that achieving normalcy (or some semblance of it) is important to the smooth operation of this factory. Hopefully this look back at the fundamentals helped to contextualize some of the more advanced concepts in molecular biology, and I hope you’ll now have a deeper appreciation for the elegant efficiency of the body.

Melecia Wright is a PhD student in Nutrition Epidemiology at the University at North Carolina, Chapel Hill. She graduated from Princeton in 2011 with a degree in Molecular Biology and a certificate in Environmental Studies. Melecia loves food and enjoys engaging in discussions pertaining to agriculture, nutrition biochemistry and the epidemiology of food-related lifestyle diseases.

[Now for some more-technical additions for the biochemically inclined...]

If the status quo works for you then working to preserve it should be foremost on your mind. How might this be achieved?

  • You may rent a new part for the machinery that De-ruby uses to temporarily increase her ruby output. Biological example: allosteric inhibition/enhancement where an enzyme receives a temporary add-on to alter its performance rate.

  • You may purchase a fixture that is more rigidly attached to the machinery. Biological example: covalent phosphorylation/dephosphorylation for altering enzyme activity, this requires a chemical reaction, unlike the allosteric modification.

  • You may have intermediate supervisors which survey the general state of affairs and direct workers as necessary (hormones like glucagon and insulin work to initiate cascades that achieve a certain end—like altering blood glucose levels).

  • If there’s a huge change in the market and larger, more structural changes are needed you would need to hire a chief operations officer who would organize those macro-level fixes — like hiring new Mickies if Mickie needs assistance. This is akin to altering gene expression, it’s pretty high-level stuff, you only escalate to the chief operations guy if you’re sure that you’ll be needing much more out of a given enzyme than you can currently get. So a few days into a new exercise regimen, for example, alterations in gene expression can produce new enzymes and other proteins to help cope with these new demands, building muscle, increasing blood flow to these muscles, etc.

So with multiple mechanisms for regulation, you would select the one that best neutralizes the threat to smooth factory operation. Vigilant policing of the processes described here should help you to maintain an incredibly efficient organism.

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