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.