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.)