Richard Cranium

OK, can someone distill the important parts of the "starvation" - how-and-why-of-glucose thread?

I'll have to admit ignorance of the subject, it's been a long time since I cracked open any of the books regarding these metabolites. I need a backgrounder on ketones, and other hormones involve fatty-acid mobilization and glucose preservation during severe caloric restriction.

On some note, would be the difference between what happens to someone who maintains a long term caloric deficit that includes activity, and the relationship of basal metabolic functions in those individuals who experience a long term caloric deficit through fasting.

Again, what I wanted to know, where does glucose come from in the absence of dietary carbohydrate? {after glycogen depletion}
And what is the caloric requirement of glucose in proportion to overall basal metabolic needs?

In anyone has good [free]journal links, by all means post them or PM me.......by cutting and pasting the text.

Enthalpic

Pictures are worth a thousand words. You can see that both carbs and protein, but not fat, can feed the pyruvate pool.

As for the minimum amount of carbs, the data I have found suggests that:
-At about 20g carbs per day the body will not build up ketones.
-At about 50g carbs per day gluconeogenesis is completely halted, as monitored by nitrogen balance studies.

531Aussie

Google 'gluconeogenesis', which is the formation of glucose from a non-carbohydrate source



this is straight to the point:

https://en.wikipedia.org/wiki/Gluconeogenesis

DannoXYZ 

Here's another link that shows specific steps in the metabolism of each of the substrates for gluconeogenesis: lactate, pyrutate, amino-acids, glycerol, propionate:

IndStateEdu - gluconeogenesis

By far the largest portion of glucose from gluconeogenesis comes from pyrutate, amino-acids and lactate; the ratio of which is dependent upon the hormonal state of the body, which is based upon the glycogen/glucose levels, which is based upon exercise-rate and ingested calories, etc, etc, etc.


Aren't those minimum carb-intake based upon exercise-levels? Or are those average values for average humans with average daily exertions?

Enthalpic

That would be based on the 2000kcal/day standard. Furthermore, as the minimums primarily reflect carb usage by the brain, sticking to the minimums would surly compromise high intensity athletic performance. With some adaptation, athletes can exercise at low intensities on a high fat-low carb diet. But lets not confuse minimal and optimal.

!!Comatoa$ted

Most, if not all hormones are interconnected and may have an effect directly or indirectly on each other, and this means that the hormones involved in fatty acid mobilisation are numerous.

When there is a decreased circulating glucose there will be less insulin as well. Insulin, an anabolic hormone, is stimulated by hyperglycaemia, glucogenic amino acids, glucagon and to an extent vagal nerve stimulation. While (nor)epinephrine will inhibit the release of insulin, even though it acts to increase blood glucose. (Nor)epinephrine stimulates the release glucagon, and together these hormones stimulate lipolysis.

Lipolysis itself produces a tremendous amount of substrate in the form of aceytyl co-a so much so that the TCA cycle cannot handle it all, some of this spills over and is eventually enters ketogenesis to become a ketone. Ketones can then be used by the body as energy. When the ketone is used for energy it is converted to bi-carb to regulate the acid base balance.

The caloric deficit you speak of may depend on how much the deficit is and what kind of nutrients are being consumed. In most conditions the body has an absolute need for glucose, and to supply it the body will use glucogenic amino acids to produce it. To do this it must used some monomer unit of protein. So when protein is broken down some amino acids will be used to produce glucose and some will produce ketones.

In the case of starvation that has been going on for several days, blood glucose will be low; this means that insulin levels will also be low, and as a result glucose entry into cells will be low. Insulin is an anabolic hormone that is used to build fat and muscle among other things. It also inhibits catabolism of protein and fats. On the other hand in a fasting state of several days there will also be an increase in the hormones cortisol, epinephrine and glucagon. The hormones are catabolic and act to increase the level of glucose in the blood (diabetogenic). This is done by stimulating protein degradation, lipolysis, fatty acid oxidation and ketogenesis. In turn these hormones mostly inhibit the secretion of insulin. Initially this is done to maintain glucose above 2.5 mmol/L in order to supply the brain and red blood cells with glucose, which interestingly enough do not need insulin to absorb glucose. Your body also tries to limit the breakdown of muscle by supplying ketones from free fatty acids in order to fuel the liver, brain and muscles, but your bodies reliance on glucose will cause protein degradation for gluconeogenesis and ketogenesis.

If starvation lasts for a few weeks the body will start to rely much more on fat for energy, in part because there is not as much protein available, and the protein that is left is growing ever more important. After about 2 weeks the brain and muscles will use ketones as their main source of energy. This reliance in ketones may produce more than can be utilised by the body and the acid base balance may be affected. After about 2 weeks the body starts to slow down significantly to keep you alive as long as possible. This results in decrease of glucagon and (nor)epinephrine, among other diabetogenic hormones.

When there is an absence of carbs in the diet the body will use amino acids to form glucose, these come in the form of protein. The interesting part about protein is that ones small intestine provides ~20-30 grams of protein a day. This happens because there is a huge turnover of cells in the small intestine. As old cells are sloughed off the are reabsorbed by the huge surface area of the intestine and broken down into their monomer units. Most protein is absorbed in the small intestine, in the jejunum and the duodenum. Only about 5-10% is eliminated in the stool.

If I come across any journal articles I will send them to you, but most would probably indicate something very specific relating to hormones, ketones, and what not.

The above is very general, if it were not I would need to type out a textbook. There are many more hormones that are involved and they can have tremendous effects if there is some sort of pathology present, individual variation, and general context. The hormones mentioned also have many other effects on the body and there are also a great deal of enzymes that may control, or be controlled by hormonal action, and the action of c-AMP ATP and ADP, among many other chemicals that are present in the body. Depending on how far you are willing to delve into the minutiae there is lots that is known, and there is infinitely more that is not known.

Richard Cranium

Thanks for ALL the posts. I've have read each of them and explored and read much of info supplied by the links. I thought I had a pretty good idea of what "goes on" with respect to the most important metabolic pathways, but realize now, I have forgotten many of the details surrounding alternate pathways as well as some critical details of how basal metabolic activities must continuously support various organ tissues.

This thread is an excellent exercise in revisiting an overview of nutrition, metabolism and diet.


I think I get the gist of the relationship of pathways with respect to glucose levels.
Gluconeogenesis cannot be considered to be a reverse process of glycolysis. A state of reciprocal regulation exists between glycolysis and gluconeogenesis. (can't coexist in a cell) - Cofactors of each pathway, inhibit activity of the other pathway. In general, negative effectors of glycolysis are positive effectors of gluconeogenesis.

The glycerol "backbone" of lipids can be used for gluconeogenesis. And protein, likewise, contributes to the pools of cofactors necessary for eventual gluconeogenesis.



More accurately; is there a minimum dietary carbohydrate level that will forestall or reduce the negative effects of metabolites resulting from long term caloric deficits?




Ok, so is it a fact that a specific minimum carb ingestion will inhibit or halt ketone accumulation? If in fact such minimum did exist, how would the timing of the carb ingestion affect homeostasis of competing metabolic processes?
Five grams every 6 hours is significantly different than 10 grams every 12 hours. What about drip?




Wait a second, I thought that some gluconeogenensis exists despite dietary surpluses.

Thanks again, great discussion.

Enthalpic

The liver is a powerful organ, and it is already based on the “drip” system. Timing of meals plays only a small role. However, insulin and glucagon are pretty powerful, so I won’t say it has no effect. At very low carb intakes I imagine all the carbs come from sauces or coatings on their meats and leaves (something like 5g 4 times daily).

I was careful to word those comments in a way to show that the processes may still be occurring; just the detection method is no longer sensitive.

So more correctly, at about 50g carb/day the amino acid oxidization rate (determined by radioisotope tracer studies) will be similar to controls.

However, we know from dannos quality link that the glycerol backbone of adipose tissue stored triacylgycerols is ensured of being used as a gluconeogenic substrate since adipose cells lack glycerol kinase. In fact adipocytes require a basal level of glycolysis in order to provide them with DHAP as an intermediate in the synthesis of triacyglycerols. So the process is still occurring, but is of insignificant magnitude.

!!Comatoa$ted

To what extent do you think you can control that with exercise, and the timing of carb ingestion?

NoRacer

Google: Keywords = "ketogenic diet" weight loss

Richard Cranium

BOING ! Duh, I feel pretty stupid now, yes indeed, if I simply would have remember all the studies surrounding Ketogenic diets or for that matter, just investigated ketoacidosis, I would have stumbled on most of what I wanted to review.

I remember these exact kinds of headaches when I studied this crap the first time around.

Anyway, here are the kinds of "big picture" principles that I've remembered.

Cofactors of given metabolic cycles can be both precursors and inhibitors of other processes.
( I use to think of an abundance of substrates as either being enzyme-like or neutral to a process.)

The other reason for my misunderstanding gluconeogenesis was in not accounting for alternate pathways to "stand in" for a non-reversible metabolic pathway.

Standby, a new "stupid Richard Cranium" thread is on the way. This time we'll disect just what the hell goes on when you eat something...........