Zombie Metabolism: Nutritional Requirements

Introduction

I'm sure that when it comes to zombie metabolism, the first question has got to be 'Does the zombie diet meet its basic nutritional requirements?'.

Before the government fell, we were bombarded with nutritional advice, five-a-day, less cholesterol, more omega-3 oils, and now... let's just say, trans-fats are not my number one concern! And as for government advice? I'm pretty sure (no-one else believes me) that it was the Shadow Secretary of State I saw the other day, face-first in a dead dog... I'd recognise that comb-over anywhere.

But zombies don't follow government advice, mostly, they just follow us! (Ha! Sorry about the zombie humour, but if you don't laugh, you cry, etc. Though as long as you keep the noise down, either is good...)

Living on a diet of mostly meat and entrails, is it possible that they may begin to suffer from malnutrition, and eventually die.. properly? We hope so, but the news isn't good, human tissue may supply them with a surprising amount of their basic requirements. 

I used my Stryer for kindling a long time ago, so I will just have to go on memory. I'll start with the most obvious:

Protein

We all know that meat is an excellent source of protein. Human beings are capable of making a lot of amino acids themselves anyway. Many of these can be made from the intermediates of the citric acid cycle (we'll talk about that more if I'm still alive and not undead, later), glutamate being the most obvious. There are a number of amino acids that can be synthesized from other amino acids as well,
such as tyrosine from phenylalanine, which are also not essential to get in the diet, assuming that you can eat the precursor.

What about the essential amino acids? Those that we have no ability to make at all? Well, since the zombies are eating us, it stands to reason they will have access to all the amino acids that a human being needs, since they are in fact, eating human beings.

Fatty acids

This is a lesser known fact, but there are some fatty acids, absolutely essential for human health, that we can't make. But bad news, since many of these are used in the phospholipids of cell membranes, the zombies are again most likely getting what they need.

Having said that, it is not sufficient to simply get enough of these fatty acids. For optimum health, they must be consumed in the correct relative amounts. Back in the day when people used to worry more about what they ate, than about what ate them, most of us needed to eat more omega-3 fatty acids. A diet too high in omega-6 fatty acids may have increased the risk of cardiovascular disease, and perhaps even depression. Brain tissue is highly enriched in omega-3 fatty acids, but despite the well-known stereotype of the brain-loving zombie, they actually tend to stick mainly to the middle, where bones don't get in the way. 

Our meat, on the other hand, is probably relatively high in omega-6, but zombie hearts don't beat anyway, although they do look pretty depressed...

Carbohydrates

Diets were relatively high in carbohydrates back in the good ol' days, and the thought of worrying about the potential of carbs for weight gain makes me all nostalgic... Carbohydrates are not, however, an 'essential' part of the diet for human beings, because we can actually make glucose via the process of gluconeogenesis. But is this relevant to zombies? Only the liver (and the kidneys, at a much lower level) are capable of synthesizing glucose and exporting it. On the other hand, some tissues may carry out gluconeogenesis, without exporting the glucose, due to their lack of the enzyme glucose-6-phosphatase. Glycolysis is an important pathway, used by pretty nearly every living organism in the world, and I think it is likely to be equally important in the living dead organisms, especially considering their lack of circulation. I don't want to go into too much detail here, but this does merit further analysis.

In any case, both muscle and liver store glycogen, which may constitute a sufficient source of glucose for your average zombie, while their high protein diet may provide sources for gluconeogenesis.

Minerals

I wasn't going to mention iron, as zombies clearly get plenty of it! But then it occurred to me, it might not be clear why they need it - are there anaemic zombies? Well, next time you go out, while you are hacking your way through the hordes of the undead to loot your local Asda, just pay attention to the way that zombies don't appear to have any blood - plenty of slime and sticky black stuff, but no blood. You'll see, zombies don't so much bleed, as ooze. So perhaps they don't need iron as much as we do. But there are many enzymes that require iron atoms for their function, aconitase (citric acid cycle) for example, and the complexes of the electron transport chain often contain iron-sulfur clusters. This goes for many of the other minerals, such as zinc. They are often found in enzyme active sites, altering the ionisation states of amino acid residues or substrates. 

So minerals are undoubtedly essential for zombies, as even zombie enzymes will need minerals for their activity. Unfortunately, since they are eating us, they probably get enough in their diet.

There is one exception to this general rule - calcium. Great sources of calcium include things like dairy products, and broccoli. Not high up on the zombie food preference list. In us, the best source of calcium would probably be our bones, which zombies don't eat. The effects of calcium deficiency on zombies are quite obvious, and to our benefit. Their bones are extremely brittle and breakable, which is why it is so much easier to smash in the skull of a zombie, than that of another human attempting to take-over your territory.

Vitamins

There are lots of different vitamins, with lots of different recommended sources, but in general, we can say that we are probably a good source of all the vitamins that zombies need. Although there are two vitamins in particular that deserve a mention:

Vitamin C: Ask the average person about the best sources of vitamin C, and they will start talking about fruits and vegetables. So this might lead the average person to conclude that zombies will come to suffer from scurvy, and then to hope that their teeth will drop out, and they will be unable to chew on us (we've all thought about it at one time or another, haven't we?). But I'm afraid that these are idle hopes. The reason why meat is not usually considered to be a viable source of vitamin C, is due to the effects of cooking.

When fruits or vegetables are cooked, the vitamin C content decreases, roughly in proportion to the duration of cooking. (Please note that the bioavailability of other vitamins may increase, due to the breakdown of cell walls - this is why, when scavenging for food, fruit and vegetables should be prepared in a variety of ways, if the sound of cooking doesn't attract nearby zombies.) Since meat is normally cooked quite thoroughly, the vitamin C is all but destroyed. Zombies don't cook, which means that we do constitute a source of vitamin C. Sorry.

Vitamin D: Vitamin D is quite hard to obtain from foods, but is actually made in our skin on exposure to sunlight. Zombies don't go in for sunblock, and can be seen wandering around even in the middle of the day, when sunlight is at its most intense. However, if they are mostly covered in clothing, or if they have lost most of their skin, they may be suffering from a vitamin D deficiency, which could contribute to the weakness of their bones. Now I haven't actually seen any zombies with rickets, but come to think of it, zombies stuck in the London Underground are easier to smash than most...

Conclusion

So there we have it. With a few exceptions, it seems likely that the zombie diet does supply their basic nutritional requirements. To those who look at their hanging flesh and emaciated figures, the festering sores and the balding scalps, and say to themselves, 'they look pretty malnourished to me', we should remember that the zombie diet doesn't need to maintain optimum health and vitality, it just needs to keep them shuffling along. Remember, the zombie plague is a disease, not a lifestyle.

Zombie Metabolism: Introduction

This is the first in what will hopefully be a series of posts discussing a topic of obvious importance: The Regulation of Metabolism in Zombies.

Introduction:

Zombies, though difficult to capture and study, present a fascinating subject for research for all those who are interested in metabolism. Topics such as appetite regulation, nutritional requirements and waste excretion all present an intriguing mystery to fans of metabolism, such as myself.

Many times, while on the run, hacking my way through emaciated, stinking, yet animated, corpses, I stop to wonder (well... I don't stop, obviously) just what adaptations zombies have made to their metabolism that gives them their striking characteristics.

Zombies obviously live on a diet consisting mostly of meat, i.e protein, which, in human metabolism, would explain their extremely lean physiques, but presents a conundrum in terms of their insatiable hunger.

How do zombies excrete waste? They continue to feed on human flesh even without function internal organs, such as the small intestine, kidney or liver.

How do zombie muscles function? They don't move very quickly, but show a fair amount of strength, implying a focus on aerobic, rather than anaerobic metabolism. But in the absence of a fully functioning circulatory system (decapitated zombie heads continue to make biting motions), how is the oxygen delivered?

As you can see, a discussion of the possible alterations in the core metabolic pathways that may occur in zombies, has more than enough depth to intrigue even the most apathetic biochemist. Though we do confess that how they metabolise human flesh is of secondary importance to making sure they do not feast on yours...

More to follow...

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

Make Yourself Amazing

MYA - Making Fat Fantastic!

With millenia of experience, our specially chosen enzymes and engineering processes can offer the full range of chemical modifications. We offer a range of affordable and flexible finance packages so that you can achieve the chemical structure you have always dreamed of.

Don't settle for the structure fatty acid synthase gave you - make yourself amazing.

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?

The Apprentice: Metabolism

In metabolism, times are tough, substrates hard to come by...

To get what they want, the contestants will have to face the challenge of a half-life.

This week on The Apprentice: Metabolism...

The Task:

Buy compounds, metabolise them, and sell the product.

The Team Names:

Synthesis - Aconitase said it came to her in a dream.

Flux - Fumarase suggested it, and nobody else had any ideas...

Team Leaders:

Synthesis chose Fatty Acid Synthase because she claimed to be 'creative'.

Flux chose Alpha-KG Dehydrogenase, because nobody else had any ideas...

The Strategy:

Synthesis - Protein Kinase A wanted to phosphorylate the compounds, Acetyl CoA Carboxylase wanted to carboxylate them. The Glucose-6-P Isomerase said it was all the same to her, and that everyone should focus on the delta G if they wanted to win.

Flux - Somebody suggested 'This is a cell', and they went with it, because nobody else had any ideas...

Who got fired?

Synthesis lost, because 'creativity' has a positive delta G, and Fatty Acid Synthase failed to realise she needed to couple her creativity to an exothermic process in order to get any work done. Malate dehydrogenase got fired, on account of not knowing when to shut up.

Metabolism for Geniuses

Are you tired of having metabolism explained in a context you can relate to?

Sick of being told that you don't have to learn the structures "off by heart"? (As if there were any other type of learning!)

Then this book is for you! The authors of  'Metabolism for Geniuses' know what everyone else has pretended to forget...

METABOLISM IS SUPPOSED TO BE BORING AND CONFUSING.

This book makes a great gift for friends whose confidence you wish to destroy, and if you buy now, you'll get a free CD with all text replaced by a voice-over in a strong foreign accent.

Dear Miss Metabolism...

(Mouse over the purple text for explanations.)

Dear Miss Metabolism,

I don't know what to do with myself, I'm so lonely. I used to be carbon atoms 4, 5 and 6 of a happy fructose-1,6-bisphosphate compound, but I guess I forgot how lucky I was, got restless, and decided I wanted us to split up.

I had seen so many of my friends going off into glycolysis and it looked like fun, and I was curious. I had no idea what a big mistake I was making, but I told my other half I wanted a trial separation, and here I am.

We found an aldolase enzyme, it wasn't hard, there was practically one on every street corner, and she promised us that it would just be a reversible reaction, that we could get back together whenever we wanted. Technically, I guess she was telling the truth. Except that after I became a dihydroxyacetone phosphate, I never saw my glyceraldehyde 3-phosphate again.

I guess I thought she would wait for me to get it out of my system, but she didn't. She rushed off into glycolysis, maybe she was feeling hurt, and left me all alone. Glyceraldehyde-3-P dehyrogenase enzymes won't even look at me, so I'm just stuck here.


Please Miss Metabolism, I'm just a foolish intermediate who didn't know how good I had it, please tell me what I should do now?


Yours,
Sad in the Cytosol



Dear Sad in the Cytosol,

Don't be too hard on yourself, you weren't to know this, but those aldolase enzymes are a bunch of home-wreckers! They always say the separation is temporary, that you can both reconcile later if you find you're unhappy, but most of the time, the two compounds just get completely broken down in to carbon dioxide and float away. It's hard being single.

Listen, chances are, your darling GAP is long-gone. All you can do now is remember the good times, and get on with your metabolism. Basically, you have three main options:

1. Mind the GAP. Finding another glyceraldehyde-3-P to settle down with might be difficult, but if you are in a cell that's doing gluconeogenesis, it's not such a long shot.



2. Get fat. Why not try an alternative metabolic lifestyle, and get reduced to a glycerol-3-P. You could settle down with some nice fatty acids (not hard on today's modern 'diets'), and live the quiet life of a triacylglycerol molecule, or the fast-paced career of a phospholipid.



3. Switch teams. If life alone really is that unbearable, why not find a triose phosphate isomerase and become a GAP yourself. Maybe by following your ex's footsteps, you might even get some closure. Be careful though, if you go all the way to becoming an acetyl CoA, you will have given up on life as a carbohydrate forever.

So think carefully before you make your decision, even reversible reactions can have irreversible consequences.

Dynamically yours,
Miss Metabolism

Check Yourself Before You...

Wreck Yourself!

(still under development...it works, just needs a few features)

Glucose the Barbarian

In a world where ATP synthesis is dominated by a handful of mitochondria, only glucose has the courage to produce ATP in the cytosol, free from the tyranny of oxygen.

Glucose the Barbarian - No compound should have to live in chains.

Hello!

Coming soon!

Adverts for metabolic pathways!

Wanted posters for metabolites!

Interviews with enzymes!

Metabolism is about to get CRAZY!!!