Wednesday, July 23, 2008

Glucose, Glycogen and Gluconeogenesis

We have glucose in our blood at all times. Where does it come from?

The first and most obvious source is from the carbohydrates in our food. Most of the complex carbs we eat, from sugar to pasta, can be broken down into glucose monosaccharides and will be absorbed into the circulation in that form. The illustration above is taken from page 329 of Lippincott's Illustrated Reviews-Biochemistry. It shows the effect of a meal of 100 grams of pure glucose. The large spike of glucose is metabolized or stored within about three hours.

If we do not eat any more food after that 100 grams of glucose, our blood glucose levels nevertheless must be maintained. If we are well-fed, our livers store about 80-100 grams of glucose as glycogen. The liver is able to convert glycogen back into glucose by means of a process called glycogenolysis. The blue line on the graph shows that, over the next few hours, the liver releases glucose back into the blood on an as-needed basis.

What if we continue to fast? Eventually, we run out of liver glycogen. If you look at the green line in the graph, you'll see that it gradually rises. This line represents gluconeogenesis, which we have discussed before. In the absence of ingested carbohydrates, and even after our liver glycogen is depleted, our liver is able to make glucose out of glycogenic amino acids and the glycerol backbones of fatty acids. It takes several hours or even days for this process to ramp up.

What if we are not fasting but are simply low-carbing? The ramping-up of gluconeogenesis is one of the reasons that people who are new to low-carbing experience something called the "Atkins flu" when they start eating 20 grams of carbs or less per day for the first time. They are not starving, but their bodies have to get used to manufacturing new glucose out of amino acids and glycerol rather than absorbing ready-made glucose from the gut. Once gluconeogenesis is established, our bodies can readily make glucose from the protein we eat.

However, even when it is well established, gluconeogenesis is not a quick-response system. Because it takes us several hours to digest a protein meal into its constituent amino acids, followed by more time to convert the amino acids into glucose, the process of gluconeogenesis is relatively slow. However, the glucose we produce can be used to replenish the glycogen in the liver, and liver glycogen is a quick-response system.

Once we are adapted to a low intake of carbohydrates, we have two means of stabilizing our blood sugar. Gluconeogeneis provides a baseline of glucose production from the protein we eat. Because the fuel needed for gluconeogenesis ebbs and flows, the new glucose made by this process ebbs and flows. Fortunately our stored liver glycogen is available to make up the difference, assuring a steady stream of glucose for baseline functions for our brain, red blood cells and other tissues that require glucose as fuel. If we need an extra burst of energy, or if a big protein meal causes our insulin to spike and our glucose to plummet, our stored liver glycogen is also there to step in the gap and provide the glucose necessary to keep our blood glucose within normal limits.

When we first start low-carbing, it's hard to understand that (if we choose to) we never need to eat another gram of carbohydrate again. But once our good friend the liver is adapted to the process, it can provide all the carbs we need through gluconeogenesis and glycogenolysis.


Unknown said...

I'm a bit confused by this.
First of all if we use proteins for glucogenesis we need a lot more proteins since as long as they're used to make glucose they can't be used for protein synthesis. So it's hard to rationalize high fat and low protein diets like the Optimal Diet

Also what about muscle glycogen? I don't think any kind of adaptation to ketones or fatty acids can substitute the ready availability of muscle glycogen that allows intensity.

So I wonder wether going low carb means also becoming slower and more sedentary.

Some authors like Wolfgang Lutz in Life Without Bread suggests 70 grams of carbs not to "waste precious proteins on making glucose you can obtain from carbs"
but still 70 grams of carbs are just enough for the need of brain and other organs.

Still glycogen should be depleted which doesn't actually address the issue of glycogen empty muscles.

Also I haven't seen any explanation as where carbs go first. What I mean let's say you're on a 10 grams of carbs diet and switch to 70 grams of carbs. Will they first replenish glycogen and maintain a ketonic brain or they will first fuel the brain stopping the ketonic metabolism and leaving the glycogen still depleted?

Stargazey said...

Hi, Danny! In response to your comments, there is a certain amount of protein that each adult individual needs to consume each day to maintain synthesis and repair. Broadly, it depends on weight and activity level. So high-fat, low-protein diets have the disadvantage that they make you gradually lose muscle mass as well as fat.

If a person does low-carb, his or her glucose requirements must come from gluconeogenesis. Of necessity, that means that extra protein must be eaten to account for the gluconeogenesis process. About 56% of protein can be converted to glucose, meaning the protein excess must be more than a 1 gram for 1 gram replacement of protein for glucose. On the other hand, in Western countries protein is relatively cheap, so I'm a little mystified why Lutz would call them "precious proteins." I can buy a pound of chuck roast for less than I used to spend on junk food at the 7-11.

The glucose made through gluconeogenesis is the same as the glucose you get from carbs. It can be and is used to make muscle and liver glycogen. It's glycogenolysis, not gluconeogenesis, that the body uses to modulate blood glucose on a minute-to-minute timescale. Chris at Conditioning Research is much better qualified than I am to speak to what types of exercise can be done on low-carb and which can't. I do know a blogger who eats only meat, fat and water and does very well in half-marathons.

If you go from 10 grams of carbs a day to 70 grams of carbs, what will happen is that you will stimulate insulin production, fat storage and cravings. Yes, you will have a bit more storage of glycogen (plus about 4 times its weight in water to keep it company). It doesn't sound like a good trade-off to me, but that's just my opinion.

Banana said...

Can you tell me anything about soluble Fiber and if it affects blood sugar? Example Fibersol 2.

Thegron said...

Hi Stargazey,

Are you still active on this thread?

I have some questions that I could really use answering :)

Stargazey said...

Yes, I'm still here. I should apologize to Banana as well. His/her question came when my husband was in a long recovery from hip surgery, which is why I posted the comment but didn't answer. Anyhow, I'll do my best.

Thegron said...

Great! Thanks.

I am a pharmacy student and know quite a bit about medicine (the field). And I loved Biochem! haha

Anyhow, I recently found out that I have a rare form of autonomic dysfunction that is caused by carbohydrates. It is unclear whether or I need to go very low carb (around 20g/day) or just lower to 75-100g/day and just eat low GI foods.

I decided to go very low carb and see how I felt and then slowly increase the carbs.

So I'm on day 6 and I'm over the flu but I'm still not all there mentally. I'm wondering if this is normal or perhaps I'm still adapting.

More importantly, since the brain requires around 120g of glucose a day, if I were to eat for example, 100g of carbs a day, how would my body get the other 20g? Can I be in a state of partial AA gluconeogenesis? That is to say, will my body get the other 20g from dietary AA's? I only ask because I know ketosis is kind of all or nothing (sort of).


Stargazey said...

1. You are of course very smart because you loved Biochem.

2. That's interesting about an autonomic dysfunction that is caused by carbohydrates. I'd never heard of such a thing.

3. It takes a few weeks to switch over to efficient metabolic functioning on a low-carb diet. If you are curious about the amount of protein you will need to eat in order to make up for the absence of carbohydrate, here is a nutrition calculator that I have found to be accurate.

4. Yes, your body can make any extra glucose it needs from gluconeogenesis. However, once you've been low-carbing for a while, parts of your brain will switch over to using ketones rather than glucose for energy. Once you're completely keto-adapted, you will only need about 40 grams of glucose a day. Not a huge amount in terms of gluconeogenesis, and that's the reason that people can survive very nicely for many years on less than 10 grams of carbs a day.

Best wishes. I hope that you're able to figure out how to balance carb intake to successfully minimize the symptoms of your autonomic dysfunction.

Thegron said...

Hey thanks for your response and well wishes. I hope to feel better soon.

When I was talking about gluconeogenesis, I was really referring to protein only. I am assuming that if one is eating enough protein every day, the body will not produce ketones because it has enough glucose from the resulting AA's.

So basically, for the time being, I do not want to induce ketosis. I'd rather go low carb and eat a high protein diet (moderate fat) for a while just to see how I do physically/mentally. Then I can decide if I want to induce ketosis or not.

When you say it takes around three weeks to become adapted. Are you referring to keto-adaptation? How long would it take to become low-carb adapted (pure AA GNG, non-ketogenic)?

Stargazey said...

Hmmm. I'm trying to think of what reference to supply for you. If you are doing low-carb, you are by definition in some degree of ketosis. Because carbs are in short supply, your body will be burning fat for energy. (Protein burning is also possible, but because it is a metabolically wasteful process, it will be avoided.)

If the conversion of fat to energy is not complete (which is usually the case), it will result in ketosis. The fat may come from the diet or from your adipose stores, but fat burning will produce ketones, no matter how much protein you are eating.

Thegron said...

Yes when I say ketosis I mean high enough levels of ketones in the blood that you start to become symptomatic (acetone breath, diuresis, etc.).

From what I remember, when you limit your carb intake, you will eventually run out of oxaloacetate for the TCA cycle (it'll be used up for GNG) and all of that acetyl-coA from fat will be converted to ketones. I could be incorrect about this however.

What about glucogenic AA's? Wouldn't they be used to create glucose for the brain in a situation where it is not getting enough?

god I love biochem :)

This is all too much trouble though. Now I'm thinking I should go up to 100g/day and see how I feel. And if I don't feel great, I can drop my intake. *Sigh*