One of the best quotes ever:

"Obesity: An Epidemic of Huge Proportions"

Yale Daily News

Encounter with a Liver

The Liver: "The King of Metabolism"

 Meeting the liver in person was a somewhat daunting prospect. Every organ knows that they owe their comfortable existence to the liver, who protects them from the sugar highs and lows that single-celled organisms struggle with on a daily basis, as well as regulating the concentration of a host of other compounds. Every organ knows that without the liver, they might starve, if the build up of toxic metabolites such as ammonia doesn't kill them first.

But there may be a secret side to the liver, a suspicion held by many, but voiced by none. Is the liver really the powerful protector it claims to be? Or does the liver suffer from an arrogance born of a genuine, but finite power? Perhaps it simply wishes to portray strength, as a cover to hide its little-known limitations?

On first meeting the liver, I was struck by the ample supply of blood, the well-oxygenated tissues, the organised, lobular arrangement of the cells. I suspected that the intent was to impress, perhaps even intimidate, though I was greeted politely enough.

"Welcome to my humble abode, Miss Metabolism. I'm a great fan of your work. Your advice to succinate dehydrogenase, for example... so insightful."

Despite myself, I was flattered, an important organ like the liver, reading my column! Though I supposed he had employees do research on me before agreeing to the interview.

"That's very kind of you, but perhaps we could begin?"

The liver laughed, "How forward! Yes, let's get straight to the point, by all means. What would you like to know?"

I hesitated, I had so many questions, some of which I was afraid to ask, but I was determined not to show any fear.

"Well, let's start with your title - the King of Metabolism?"
"Yes?"
"That is a self-appointed title, is it not?"
The liver showed no surprise, "And what of it? Self-appointed, but nonetheless accurate."

I tried to make my voice sound firm, unaffected. "But..", I pressed, "don't you think it sounds a little... arrogant?"

The liver didn't appear angry, yet. "I make sure that every tissue in the human body gets exactly what it needs, when it needs it, and I save whatever is left for emergencies. I filter and detoxify the...", the liver hesitated, searching for an appropriate word, "substances... that the body ingests, until, if you'll forgive the phrase, it is fit for human consumption. I am also one of only two organs that can make glucose, and the only one that can make urea! Need I go on?".

I could hear the menace in his voice layered subtly under the surface. It made me more determined. "You forgot to mention fatty acids..."

"Yes, I can make them... or break them."

The threat was not lost on me. "Well, I'm no fatty acid, and I'm not afraid of you," I was almost sure he hadn't heard the tremor in my words, "You are not as all powerful as you would have us believe!"

"I have never claimed to be 'all powerful'. I am simply a humble servant. When blood sugar is low, I break down my own glycogen to supply glucose to those less fortunate than myself. If the situation persists, I even break down my own proteins to make yet more glucose."

I sneered, "Quite the martyr, aren't we? But I think you're hiding something... I think you are taking all the credit, when you are just a bit player!"

The liver said nothing.

I went on, "I put it to you, that you have exaggerated your importance in metabolism!" Calmly, too calmly, the liver replied, "And upon what do you base that statement? Have I said anything to you that is untrue?"

"Oh, you have been quite honest, glycogenolysis, ureagenesis, gluconeogenesis, and probably more as well! If there's a metabolic pathway, you have probably got it! You can do almost anything! But in what amounts, liver? In what amounts?" Now I could see that I had hit upon something that made the liver nervous, and I continued at full speed. "You go on about your glycogen, supplying glucose to the masses and all that, but just how much do you actually have? I'll bet it's nothing compared to skeletal muscle! And just how many fatty acids do you actually synthesize anyway?" I could see that the liver was panicking now, and that the months of research I had done in preparation for this interview had been spot on.

"You know what I think? I think that hardly any of the fats in the adipose tissue were made by you!"
"But the triacylglycerol..." the liver faltered. "I'm not talking about lipoproteins!", I countered, "I'm talking cold, hard fatty acids!" The liver could not even think of a response.

"I've heard rumours about you, liver.", I leaned in closer, and the liver shrank back, because now it was afraid of me. "I've heard that you normally only make fatty acids to get rid of excess malonyl CoA. I've heard that most of the amino acids you use for gluconeogenesis are just waste from other tissues. For that matter, I've heard that most of the glucose you make is leftovers from muscle glycolysis!" The liver began to sob quietly. "I've heard that you serve us up our own leftovers, and then expect us to grovel for it!" This last statement was almost whispered.

I leaned back, satisfied that I had gotten to the truth at last. I watched the liver, its aura of importance, its swagger, now completely deconstructed. It was pathetic. I got up and started to walk away.

But then the liver spoke up, perhaps hoping to salvage some small dignity. "They need me you know. Nobody else can look after them the way I do. Maybe I do serve them leftovers, but in starvation, its all we've got! And maybe I can only do small amounts, but what matters is, it's enough... it's enough." He continued mumbling through the sobs, but I felt no pity. I just remembered how he had intimidated us all, lording it over us, taking all the credit like he was the only organ playing a role in metabolism.

As I was leaving, I turned back and said, "By the way, I can see your scar tissue.", and then I left.

Even as they faded, I could tell the sobs were getting louder.

Cheapskates!

When metabolic cycles go out to dinner...

The Metabolism Olympics

Although there will be lots of substrates competing for active sites this year, few enzymes are as non-specific as the fatty acid metabolism enzymes, so the competition is expected to be fierce.

My ATP is on the omega-3 fatty acids. What do you think?

Succs to be me...

Dear Miss Metabolism,

I am a complex II, and I am being bullied. I work just as hard as any other enzyme complex, I contribute as much as I can, but the other complexes make fun of me because I can't pump protons like they do. Even Complex V teases me, and she lets protons back in!!!

How is that fair?

I can't control the redox potential of succinate or ubiquinone, any more than they can control the redox potentials of their substrates and products.

I wouldn't mind so much, but they're making my little FAD depressed. Sometimes I hear him crying himself to sleep at night. Its not right for a little prosthetic group to hear his enzyme being humilated like this, its bad for his self-esteem.

I've tried explaining these things to the other complexes, but they just won't listen!

Any advice on how to handle this?

Yours truly,
Succs To Be Me


Dear Succs To Be Me,

The first thing I want you to do is stop talking about yourself like that! You are an important complex, and don't ever forget it!

Its true that via Complex I, the electron transport chain can continue along without you, but there is more to a half-life than transporting electrons. Its true that you don't pump protons, but there is more to a half-life than generating electrochemical gradients.

Perhaps this sounds cliche, but I am pretty sure they are just jealous. Lets not forget that the succinate dehydrogenase part of you is absolutely integral to the citric acid cycle, and what would happen if you stopped functioning? I'd like to see them get much in the way of reducing power then, the supply would become pretty scarce, I can tell you!

And in addition to all that, you might have a role in oxygen sensing and tumour suppression too!

I wouldn't be surprised if Complex I was the one instigating all this, after all, you are the competition, and he probably sees you as a threat. As for Complex III and IV, they should be ashamed of themselves, how can they make fun of you while still accepting your electrons? They would do well to remember that the real reason they can pump protons is because of the difference in the reduction potentials of their substrates and products, and not because of any intrinsic property that they have.

And my sympathies to your little FAD, although we coddle and fuss over them, don't worry, prosthetic groups are alot tougher than we give them credit for, he'll be alright, as long as you don't take their insults to heart.

Having hopefully activated your self-esteem a little bit, let me just say this. Bullies are insecure, and they crave a response from those they bully. To paraphrase a human saying, 'Enzymes need substrates'. Show them just how much you don't care, and if they really get on your nerves, take a break for a while... when the citric acid cycle grinds to a halt, they'll be begging you to start transporting electrons again.

Keep your chin up,
Miss Metabolism

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Kidney Cancers: Major rise 'linked to obesity'

Obesity is fuelling a major increase in the number of cases of kidney cancers diagnosed in Britain, expert humans have discovered.

Cancer Research UK, sworn enemy of tumours everywhere has published figures revealing that we have had over 9,000 cases in 2009, compared with just under 2,300 in 1975. We kidney cancers are obviously overjoyed to see our numbers rising so greatly, but Cancer Research UK is only publishing what we consider to be good news in an effort to eradicate us!


Cancer Research UK, not satisfied with decreasing the number of smokers (we were working on that one ourselves, with admittedly different tactics), is now moving on to obesity with disturbing enthusiasm. Apparently, obesity increases the 'risk' of developing us kidney cancers by about 70%, compared with smoking, which increases it by about 50%.


Too many people know about the cancer risk of being overweight, but Cancer Research UK are using every means at their disposal to increase the spread of this sensitive information. Not satisfied with developing poisons that cut off our very blood supply - CRUK are now trying to prevent us from ever existing in the first place!


When will this bigotry stop?


Many of us stood by silently when measures to cut smoking were introduced, thinking that we would be OK, while the numbers of our brothers, the lung cancers, were rapidly decimated. But now the humans have come for us, and all the other cancers linked to obesity - breast, bowel, womb... the list goes on. It is in our nature to suck the life out of the humans, so why do they hate us? They say it is because we kill them, but I think the real reason is that they hate our freedom!


So what can we do about it? Any suggestions?