Sunday, July 26, 2009

Glycosylation and Glycation

In light of recent discussions about increased protein intake producing a rise in blood sugar, this seems to be a good time to repeat a post from 2008. It helps explain why elevated blood sugar can present potential long-term health risks.
When proteins are assembled in our cells, sometimes specific sugar molecules are attached to them in carefully-defined ways. This is called glycosylation. Enzymes add the sugar molecules to help proteins fold properly and to route proteins to various places inside and outside the cell. Glycosylation patterns also help our bodies to distinguish proteins that are "self" versus "not-self" and are useful in immune responses. Glycosylation results from controlled reactions and is important for our biochemical wellbeing.

When we have glucose in our blood (and if we're alive, we do), sugar molecules are also added to proteins in a random fashion. The random addition of sugar molecules to proteins is called glycation. If only single glucose molecules have been added to a protein, when the blood sugar level drops, the glucose can detach and the protein will again be normal. But if blood glucose remains high, more sugars will be added. These will rearrange and crosslink, eventually producing something called an Advanced Glycation Endproduct or AGE. One example of an AGE is hemoglobin A1c, the form of hemoglobin found elevated amounts in the red blood cells of poorly-controlled diabetics. Evidence suggests that many other proteins in our bodies are also converted into Advanced Glycation Endproducts by elevated blood sugar. Glucose and fructose in the blood interact with and crosslink these other proteins in our bodies, forming AGEs that accumulate in our eyes, kidneys, arteries, nerve endings, joints and skin. The end result of AGE accumulation can be retinal disease, kidney failure, atherosclerosis, peripheral neuropathy, frozen joints and cracked skin.

Although our bodies have mechanisms to cope with the identification and disposal of AGEs, the AGEs gradually accumulate and stiffen our tissues. The elasticity of youth is slowly replaced by the physical degeneration of old age. In other words, crosslinked AGE proteins produce in us the symptoms we associate with old age. This happens in all people, but the process is made worse and happens more quickly in the presence of elevated blood sugar.

(The illustration is taken from the cover of the journal Science, March 23, 2001.)

11 comments: said...

Very informative explanation. It makes me take my Type 2 diabetic A1c numbers even more seriously. Thanks.

Unknown said...

It always helps to be reminded of information you have already shared. Some are new readers, some just do not remember. Thank you for the time you take in deciding what to post and to prepare it carefully.

Stargazey said...

Thanks, Jim and Stormycatalyst! The complications of elevated blood sugar have such a slow time of onset that they are easy to ignore. I needed to be reminded myself that they are nothing to trifle with.

Anne H said...

My brain needs a Coke just to figure it all out!
Stargazey - you need to write a book :)

Stargazey said...

Believe it or not, I originally started this blog as a "platform" for writing a book someday. But I'm having too much fun blogging, and somehow I can't quite imagine a biochemistry book as a bestseller. :-) It would definitely work as a cure for insomnia, though!

Amber said...

I have a couple of questions.

1) in the arctic explorers diaries they give their dogs the lean meat - why do the dogs not get sick (rabbit starvation) - why do we need fat to process the protein and not the dogs?

2) why do we fall out of ketosis so quickly? Surely the caveman/paelo man would love sugar like we do? If I go in the fields in Autumn there are tonnes of fruit. A hunter would surely pick at the fruit as hunting and so at some times of year get a larger sugar kick? But then hes hunting while hes undergoing sugar withdraw and also while his body is now burning sugar and struggling to keep on an even energy level? Why does changing from sugar to fat burning seem to take so long? If you pick at foods that are about would it be enough to mean that the caveman would have induction flu all the time?

Stargazey said...

Amber, I don't have any science to answer your questions--just speculation. So here goes.

1. As I understand it, the reason people experience rabbit starvation is that their livers can only convert protein into about 1600 calories of glucose per day at a maximum. There is probably a large metabolic cost to do that conversion, and all things considered, they don't get enough energy to sustain life for very long.

Dogs may have a more efficient way of metabolizing lots of protein than people do. Their livers may be better at doing gluconeogenesis, and their metabolism may be better at getting rid of the excess amino groups. Just speculating, but in the wild state, the alpha and beta dogs/wolves would probably have eaten most of the fat from an animal that was killed. The rest of the pack would have had to develop metabolic pathways that permitted them to survive on a low-fat/high-protein food supply.

2. Again, as I understand it, a young person is able to switch easily between various food sources--from carbs to fat to protein--as needed. If his body becomes accustomed to a high-carbohydrate diet, the enzymes for gluconeogenesis are only synthesized in small amounts because they are seldom used. When such a person starts an Atkins-type diet, his body has to rev up its gluconeogenesis machinery once again, and that takes a few days. Many of his tissues that are used to running on glucose will also have to switch over to running on ketones. While all of that is happening, he is in induction flu because his body is not metabolically prepared to handle the type of food he is feeding it.

Once the low-carb metabolic pathways are up and running, he can then pig out on apples and berries when they become available in the fall. They will raise his insulin and will be stored as fat for the winter. Once winter comes, he will be back into a low-insulin state and will be able to mobilize his fat stores easily, thus avoiding the problem of starving over the winter if he is unable to kill enough animals at that time.

Stargazey said...

Forgot to add, if our hypothetical low-carber is not a hunter-gatherer but instead is living in a place where he has ready access to supermarkets, then the problem of starvation over the winter does not exist. He will have put on fat for the winter, will not need to use it, and will still be carrying the excess fat when spring rolls around.

I hope all of that makes some sense. :-)

Amber said...

Thanks! (always seems a bummer that low carb you cannot have an 'off' meal, yet low fat allows you an 'off' much more easily)

diff said...

Thank you for explaining these things.

For the past 12 months, I have been practising Bikram Yoga. There is a lot of compression of joints and organs (folding yourself at certain points) followed by release, or 'dead body pose' (where you lie flat on your back). In the class, it is suggested that the movements being organised in this way is designed to encourage blood to flow through the areas that have just been hard at work. I have found the yoga to be very beneficial in the way I feel in a number of ways (increased range of movement-including improvement of old injuries, clearer thinking). Do you think increasing the blood flow in this way helps to move AGEs?

(Type 1 diabetic for 22 years).

Stargazey said...

It's possible, diff. The tissues in our bodies are replaced at differing rates over the years. Some, like neurons, are replaced very slowly or not at all. Others, like the cells lining our gut, last only a few days. Most tissues have a halflife that is measured in years or decades.

Many of these tissues include glycosylated cells, and presumably some AGEs could be eliminated that way. I don't know if your yoga techniques would affect the rate of replacement. It's always possible to come up with theoretical constructs of how a process might work, but it's much more convincing if somebody does a well-designed study and checks it out with actual data.