Glycolysis & Gluconeogenesis: How the Atkins Diet Works
Well, have you ever wanted to know how the Atkins diet worked? This module will try to explain it by talking about the process of gluconeogenesis.
This is in fact the body's response to starvation, fasting and diet.
Your heart and your brain require glucose for energy.
They can't use fatty acids for example from fat breakdown.
It turns out that glucose stored in the liver or kidneys largely in glycogen, lasts about 4 to 6 (actually it should say 4-6) hours, and yet we can survive for weeks withoutfood.
So how is this possible? Well the answer again, is gluconeogenesis.
Gluconeogenesisis is the synthesis of glucose from non-carbohydrate sources.
This provides the glucose that will be necessary for neural tissue and cardiac function, when in fact dietary glucose is in short supply.
Well, this is the body's response to fasting.
In essence, by the way, this is very similar, I should say to a stress response.
And some of you may know a little bit about stress responses.
The hypothalamus is a neurosecretory gland at the base of the brain.
It releases neurosecretory hormones or neurohormones, which stimulate the pituitary gland very nearby.
Among the responses of the pituitary gland is the production and release of adrenal cortical tropic hormone or ACTH, which you may have heard of.
That stimulates the adrenal glands at the cap or top of the kidneys to release glucocorticoids, such as cortisone and corticosterone.
and these hormones, these steroid hormones, have a number of effects.
They affect skeletal muscle by increasing the transcription and translation of proteolytic enzymes, enzymes to catalyze the digestion of proteins.
These are called collectively, proteases.
So you see that proteases are enzymes that catalyze the breakdown or hydrolysis of proteins to amino acids.
The glucocorticoids have other effects as well, on many tissues.
In most tissues including adipose tissue.
glucocorticoids stimulate an increase in the amount of enzymes called 'lipases'.
And lipases are enzymes that catalyze the breakdown of triglycerides, the hydrolysis of fatty acids from glycerol.
And finally, glucocorticoids travel to the liver where they induce the transcription again, and translation of a number enzymes referred to collectively as 'bypass' enzymes.
We'll talk about exactly what they do in just a second.
But the function of bypass enzymes is to facilitate the conversion of non-carbohydrate sources, such as amino acids, into glucose in the liver.
also to some extent in the kidneys.
So here's gluconeogenesis.
And watch for the significance of these biologically irreversible reactions that we talked about, largely when we discussed glycolysis.
So on this illustration is a summary of glycolysis showing the showing the various steps, not in detail but, in summary form.
And the steps numbered 1, 2 & 3, catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase are the three biologically irreversible reactions ofglycolysis.
And of course as you can see at the bottom, the product of of glycolysis under anaerobic conditions of course is pyruvic acid (or pyruvate).
If you are dieting or fasting, even sleeping or god forbid, starving, this sets of a series of hormonal events that I just showed you.
that reverse (among other things), reverse glycolysis in the liver.
As we saw just a moment ago, they also stimulate the use of alternative energy sources like fatty acids for energy, by stimulating the breakdown of triglycerides, freeing up fatty acids for beta-oxidation in most cells.
In the liver, and again, to some extent in the kidneys, this is what these hormonal events do.
They stimulate the synthesis of these bypass enzymes which carry out the reactions, which in glycolysis going in the forward direction, are irreversible.
And you can see the names of the enzymes that constitute these bypass enzymes.
So, pyruvate kinase is biologically irreversible.
so to get pyruvate to go back to PEP, you actually have to go through 2 steps, shown here catalyzed by pyruvate carboxylase and PEP carboxylase.
The phosphofructokinase, biologically irreversible forward reaction of glycolysis is bypassed by the enzyme fructose bisphosphatase.
And finally, hexokinase is bypassed.
That is, the hexokinase cannot go in reverse.
To GO in reverse, you must bypass the hexokinase step, using G6P phosphatase.
You may recall that we saw this enzyme earlier in the discussion of glycolysis.
Once again, these four enzymes are normally not present in the liver or the kidneys.
But during fasting or dieting or starvation, glucocorticoid hormones released by the hormonal processes I showed you, stimulate the transcription of and translation of mRNAs for these enzymes in these tissues.
Now, it turns out that glucocorticoids are actually released right around the time you wake up.
It's the kind of a diurnal rhythm, a daily rhythm.
Every morning, whenever you wake up, glucocorticoids are released.
They are released automatically, but why do you think they would have been released? Automatically they are released (whoops here we go, back again) they're released bcause at dawn, your body is supposed to think that it is fasting.
It's in a gluconeogenoic mode.
In fact glucose reserves, glycogen in the liver and the kidneys.
and in fact other cells that store glycogen, those reserves are tapped out.
In fact you are normally gluconeogenic in the morning.
And so your body has evolved a way to ensure that your you will be doing gluconeogenesis or at least have the hormones ready to prime gluconeogenesis when you wake up.
Let's take a look at the centrality of this respiratory pathway one more time (you've see in this light before).
Here it is: I just want to highlight those parts of the pathways that you see here that are in fact gluconeogenic, that is occur or happen during gluconeogenesis Lipids are broken down into glycerol and fatty acids.
The fatty acids undergo beta-oxidation, which can happen at anytime, but are especially prevalent during gluconeogenic times.
The glycerol is a gluconeogenic substrate because it enters the glycolytic pathway, where it can either go up or down depending on the cells needs for energy.
The conversion of gluconeogenic amino acids to pyruvate is shown here.
as happening at two levels: Some amino acids are converted to acetyl-coenzyme A.
Others are converted to one or another of the intermediates in the tricarboxylic acid cycle.
So once again, the respiratory pathway is central to a lot of biochemical metabolism, including the gluconeogenic response.
So why does the Atkins diet work? Because it encourages consumption of lipids (fats, which is the usual source of a lot of obesity), and at the same time allows the body to use amino acids as a source of energy rather than glucose, which is especially important because for the sustenance of neural tissue and cardiac tissue, the amino acids are in fact converted back to glucose in liver and kidney which is then released to the circulation and can circulate largely to heart and nerve tissue.
That brings us to the end to this presentation.
So i hope you now have a better sense of why the Atkins diet works and what gluconeogenesis is all about.