Metabolism and energy equivalence

[caters]

I asked people on OpenStudy this:

1 Glucose = 36 ATP
18 carbon fatty acid = 146
ATP Alanine = 34
ATP Serine = Alanine
Theronine = Glycine = Alanine
And pretty much every other amino acid gives the same amount as the others I have listed.
I am making a eukaryotic totipotent cell from its molecular components and so here is the question: After the ATP injection before the action potential and natural ion flow how is my cell most likely going to get ATP?
A. Glucose
B. Other sugars converted to glucose
C. Fatty Acids
D Amino Acids

A person responded and said that he thinks it is Other sugars converted to glucose.

I honestly thought that it was either glucose or fatty acids and not other sugars that have been converted to glucose.

[neuro]

caters,
the answer is any organic molecule that can be processed by the cell to give compounds containing carbon, hydrogen, and possibly oxygen.

Any bond between carbon and hydrogen "contains" free chemical energy, because both carbon and hydrogen tend to release their electrons rather than keeping them. The same moment an electron is transferred from a C+H compound to oxygen (which is much more avid for electrons) energy is released. A proper cell (with mitochondria) can bring this process to the end (i.e. producing H2O and CO2, no more C-H bonds) and accumulate the released energy in the form of ATP.

So you can fuel a cell with fatty acids, with glucose, with other sugars, with aminoacids (which will be metabolized to glucose first, gluconeogenesis: the nitrogen moiety wll have to be discarded), with glycogen, or any other compound that the cell can metabolize.

[BioWizard]

I agree with neuro. Except, the cell does prioritize energy sources, and that's simply due to the fact that only a few entry points into the energy extraction pathways are possible. So, the closer the starting molecule is to an entry point, the higher the likelihood that it will be utilized first. One of the main entry points is glucose, which goes through glycolysis, then oxidative phosphorylation. The other is ketone bodies, which are converted to acetyl CoA and then entered into Kreb's cycle. Fatty acids have to be broken down to Acetyl CoA, starting with beta oxidation. Amino acids have to be converted to either glucose (glucogenic amino acids) or directly to Acetyl CoA (ketogenic amino acids) before they can be utilized for ATP synthesis. Complex carbohydrates have to be broken down to monohexoses, which will all have to be isomerized to glucose before they can enter glycolysis (except for fructose, if I remember correctly, which can enter in step two of glycolysis).

[BioWizard]

i just want to add a qualifier, that what I said about fructose entering at step two of glycolysis is only true for muscle. In the liver, fructose is converted to gluneogenic metabolites which can be used to make glucose -> glycogen, or triglycerides when glycogen supplies are entirely replenished.

[caters]

i just want to add a qualifier, that what I said about fructose entering at step two of glycolysis is only true for muscle. In the liver, fructose is converted to gluneogenic metabolites which can be used to make glucose -> glycogen, or triglycerides when glycogen supplies are entirely replenished.

Well what would happen if you gave a non-muscle, non-liver cell fructose or really any other sugar besides glucose(including disaccharides and oligosaccharides and polysaccharides)?

Would you find missing links in sugar metabolism?

I mean we know how glucose is used in cells and we know normally other sugars such as galactose are converted in the liver to glucose which in turn is converted to ATP in all cells + glycogen in liver and muscle or digested in the stomach and mouth if it is multiple sugar molecules that make up the sugar.

But for example what would happen if you put galactose inside a cell that is not a hepatocyte?

All these I don't think have been done. I suppose putting cellulose inside one of your cells revs up the ATP production because it is basically hundreds of glucose molecules in just 1 unit of cellulose.

[BioWizard]

Well what would happen if you gave a non-muscle, non-liver cell fructose or really any other sugar besides glucose(including disaccharides and oligosaccharides and polysaccharides)?

For a cell to be able to to anything with a molecule, it needs to have the enzymes that can either modify or break down the molecule. This is, in a sense, similar to light and our ability to detect it. Light is visible to us is because we have the receptors in our eyes that can capture it. If we didn't have those receptors, we would not be able to detect photons in the EM spectral range we call "visible range". Similarly, any molecule that the cell has no enzymes to work on is chemically "invisible" to the cell from an energetic point of view. If a cell can't break the bonds of an absorbed molecule, then it won't be able to extract energy from it.

Quite often, cells add a moiety, such as a phosphate group, to molecules before they're broken down. The addition of the phosphate group can make the bonds adjacent to it easier to break, and since ATP is quite abundant, phosphate groups can be readily transferred under the action of enzymes called kinases.

In the case of hexoses such as glucose, fructose, and galactoses, either general (work on all three) or specific (work on just one) hexokinases can add the phosphate to generate the phosphorylated sugar. Then the phosphorylated sugar can be further processed.

Glucose can be broken down in glycolysis to yield pyruvate, ATPs, and NADH. Pyruvate can further go through the Kreb's cycle and produce lots of ATPs from oxidative phosphorylation. Thus, for any molecule (other than glucose) to go through this same pathway, it has to be first converted to glucose, or otherwise to some intermediate metabolite along the glycolytic pathway. Since only muscle and liver cells have the kinase that will phosphorylate fructose, only these two cell types can utilize fructose sugar. muscle cells have the right kinase to allow fructose to be converted to a metabolite of glycolysis, and thus muscle cells are the only ones that can directly utilize fructose to generate ATP. In the liver, hexokinase can only make a phosphorylated form of fructose that cannot enter glycolysis, but can be used to make glucose. Thus, in the liver, fructose can be used to make glucose, and then the glucose can be used to make glycogen. Once glycogen stores of the liver are fully replenished, all the fructose goes into fatty acid and glycerol synthesis, which together make triglycerides.

Would you find missing links in sugar metabolism?

I mean we know how glucose is used in cells and we know normally other sugars such as galactose are converted in the liver to glucose which in turn is converted to ATP in all cells + glycogen in liver and muscle or digested in the stomach and mouth if it is multiple sugar molecules that make up the sugar.

But for example what would happen if you put galactose inside a cell that is not a hepatocyte?

The reason the liver can interconvert these molecules is because it has the hexokinase enzyme. Any cell that doesn't have the enzymes that can phosphorylate galactose and break it down simply can't make use of it.

All these I don't think have been done. I suppose putting cellulose inside one of your cells revs up the ATP production because it is basically hundreds of glucose molecules in just 1 unit of cellulose.

Cellulose sure has a lot of energy locked up in it, but the cell simply can't access that energy unless it can first break down the cellulose into the monohexose units. We don't have the enzyme that breaks down cellulose, that's why fiber literally goes right through us. Only ruminating mammals can access the energy in cellulose (and inside cells wrapped by cellulose), and they do so by harboring bacteria in their digestive systems that can break down cellulose. That's why eating the meat of plant-eating animals is good for us. It allows us to acquire so many nutrients that we have a hard time acquiring directly from plants.

[caters]

I know but the liver does that same phosphorylation and conversion with galactose and other hexoses.

And amylase can break down disaccharides, trisaccharides, and some others molecules with multiple sugars.

This amylase is in our saliva(which is why our saliva helps cleanse our teeth), our stomach(mainly from the mouth but also gets produced here along with protease), and our pancreas.

I bet that our cells have a general hexokinase that can work with any hexose and that glucose makes the hexokinase have 1 conformation whereas galactose makes it have a different one.


Plus if our cells were to have channels for every type of hexose that would be nice because we would have even less chance of rigor mortis from Na+ deficiency which eventually makes us have ATP deficiency than we do with just glucose, amino acids, and fatty acids as metabolites.

[owleye]

I heard (in a talk on a University of California TV channel) that fructose was a bit more difficult for the liver to digest. Is there something you can add to this?

[BioWizard]

I know but the liver does that same phosphorylation and conversion with galactose and other hexoses.

The liver has a lot of enzymes that are not expressed anywhere else. It's a very unique organ that you should not use as a rule for what happens anywhere else in the body.

And amylase can break down disaccharides, trisaccharides, and some others molecules with multiple sugars.

Yes, but sugars and carbohydrates, while they contain the same glucose molecules in cellulose, have them connected differently. Enzymes are specific catalysts, meaning they will only work on specific molecules at specific locations. Amylase won't break down cellulose.

This amylase is in our saliva(which is why our saliva helps cleanse our teeth), our stomach(mainly from the mouth but also gets produced here along with protease), and our pancreas.

I wouldn't call releasing simple sugars unto our teeth "cleansing" them. Bacteria love simple sugars. But ok...

I bet that our cells have a general hexokinase that can work with any hexose and that glucose makes the hexokinase have 1 conformation whereas galactose makes it have a different one.

What are you basing your bet on? We know a lot about human biochemistry nowadays. so there's no need for much guessing with most of these things. The human genome has been fully sequenced and lots of online databses contain transcriptome data on various cell types. If you want to know whether a gene is expressed in a cell type, you can just go and look. There is also repositories that will consolidate information, and can tell you the tissue specific expression of various proteins (for instance http://www.uniprot.org/).

The enzyme that works on all hexoses is called hexokinase. Otherwise, lucokinase is specific for glucose, fructokinase is specific for fructose, and galactokinase is specific for galactose.

Thus, if you want to find which cells can utilize glucose, you need to figure out which cells have either fructose kinase or hexokinase.

Mind you, phosphorylated fructose cannot be readily used in glycolysis and has to undergo several additional steps before it can enter as glycerlaldehyde phosphate and dihydroxyacetone phosphate. Alternatively, in the liver it can be worked back into glucose in gluconeogenesis (occurs primarily in liver and kidneys).

Plus if our cells were to have channels for every type of hexose that would be nice because we would have even less chance of rigor mortis from Na+ deficiency which eventually makes us have ATP deficiency than we do with just glucose, amino acids, and fatty acids as metabolites.

There is very good reason why everything is restricted to one entry point (glucose). If every sugar we consume could directly enter metabolic pathways in all cell types, it would be incredibly difficult for our bodies to regulate our overall metabolic state. By constraining things to glucose, our bodies can have some sort of centralized metabolic control.

[BioWizard]

I heard (in a talk on a University of California TV channel) that fructose was a bit more difficult for the liver to digest. Is there something you can add to this?

It might just be referring to the fact that the liver still needs to convert it into glycolytic intermediates or convert it into glucose before it can use it to make ATP (if it enters glycolysis then oxidative phosphorylation), make glycogen (if it is converted into glucose and entered into the glycogenic pathway), or releases it into the blood stream for the rest of the body to use.

The way I see it, our bodies are only going to make direct use of fructose if we consume it immediately before an activity (one that is enough to tap into our muscles', and possibly our liver's, glycogen reserves). Otherwise, it seems like our bodies convert the bulk of consumed fructose into glycogen or fat (triglyceride). I'm not an expert on this topic, but that's my guess.

[caters]

but you see if we were to have every hexose as a metabolite we could have low BGL(blood glucose level) and still be fine because our cells would use the other hexoses.

It would also greatly lower the risk of ATP deficiency or at least when you get rigor mortis the muscles are extremely relaxed for longer that they would be otherwise.

[BioWizard]

but you see if we were to have every hexose as a metabolite we could have low BGL(blood glucose level) and still be fine because our cells would use the other hexoses.

Not really. Rather, the issue of low blood glucose would simply extend to become the issue of low blood hexose.

It would also greatly lower the risk of ATP deficiency

Maybe it would, and maybe it wouldn't. Your body is already able to use fructose and galactose, just not directly by all cells. And I already explained why restricting entry into energetic pathways to one molecule is beneficial - it allows centralized metabolic control and controlled distribution of resources between brain, liver, and skeletal muscle, and efficient re-distribution depending on need.

or at least when you get rigor mortis the muscles are extremely relaxed for longer that they would be otherwise.

ATP depletion in rigor mortis is due to collapse of the entire metabolic cycle and shut down of oxidative phosphorylation. Which means adding in glucose or any other hexose won't help.

[caters]

why would that be? If our cells were able to use galactose for example directly than our cells would use the galactose when glucose is low.

Same thing goes for other hexoses.

Also that would lower the risk of ATP deficiency because of how we would have this metabolite cycle assuming we run out of each:
Glucose-Other hexoses-Protein-Fat

Most common cause of ATP deficency:
Hypoglycemia, hypolipidemia, low protein(this is all caused by those water fast diets where all you have is water and vitamins)
Second most common cause:
Na+ deficiency(most common cause of this is low sodium diets)

[BioWizard]

Caters, I already addressed all of those points.

Our bodies are already capable of utilizing fructose and galactose (they just to be converted first, as is the case with almost everything we eat), so allowing all cells to utilize them directly isn't going to be THAT much of an advantage. In fact, it might pose a disadvantage, in that it might make it harder for the body to centralize metabolic control and resource distribution, as I already explained (twice).

[caters]

Caters, I already addressed all of those points.

Our bodies are already capable of utilizing fructose and galactose (they just to be converted first, as is the case with almost everything we eat), so allowing all cells to utilize them directly isn't going to be THAT much of an advantage. In fact, it might pose a disadvantage, in that it might make it harder for the body to centralize metabolic control and resource distribution, as I already explained (twice).

Metabolic control would not be a problem if we evolved to be able to use every hexose directly without any isomerization to glucose for these reasons:

1) we would evolve to use 1 hexose and then when we run out of that one use a different hexose
2) we would get much more ATP and possibly live longer

It would also be medically beneficial because then we wouldn't have to worry as much about prediabetes, diabetes(hyperglycemia), or hypoglycemia because glycemia means it applies to glucose and glucose only.

[BioWizard]

Metabolic control would not be a problem if we evolved to be able to use every hexose directly without any isomerization to glucose for these reasons:

1) we would evolve to use 1 hexose and then when we run out of that one use a different hexose

I don't know why this point is being so elusive to you, but the isomerization step in no way prevents us from using other hexoses for energy. Instead, it allows us to regulate our metabolism rather tightly. Our cells have differential affinities for glucose, which allows our bodies to work the way they do, and prioritize usages by the more vital organs. This rather complex system requires a coherent system of cell-surface receptors, channels, hormones, and intracellular enzymes. These are all evolved to work within a glucose-centric metabolism. If you open this system up to direct interference from other hexoses, it would be impossible to keep our bodies working the way they do now. Not without evolving an entire add-on suit of receptors, hormones, enzymes, and so on. Since evolution doesn't follow a theoretical plan and doesn't have foresight, that is unlikely to happen. There's just so many unstable intermediates, and a final result which may or may not be better than the current one.

2) we would get much more ATP and possibly live longer

This is wrong on several levels. Given a balanced diet, ATP production is not rate limited by our glucose-centric metabolism. It is more limited by how well/quickly cells can deal with byproducts of aerobic and/or anaerobic processes leading to ATP synthesis. Thus, being able to use other hexoses directly won't necessarily translate to better ATP production. In healthy adults, increased ATP production does not correlate with improved health, slower aging, or any positive health indicator. ATP production, like all biochemical processes, is very tightly controlled, and more doesn't mean better. In fact, caloric restriction can have positive health benefits.

It would also be medically beneficial because then we wouldn't have to worry as much about prediabetes, diabetes(hyperglycemia), or hypoglycemia because glycemia means it applies to glucose and glucose only.

Also wrong. These are all problems related to the glucose uptake, not glucose breakdown. So being able to breakdown hexoses doesn't necessarily fix any of these problems, since hexoses are usually internalized into cells by the same channels.

[john21wall]

Thanks for all the tips and advice