(Download) "Protein Crosslinking by the Maillard Reaction with Ascorbic Acid and Glucose" by Zhenyu Dai # Book PDF Kindle ePub Free
eBook details
- Title: Protein Crosslinking by the Maillard Reaction with Ascorbic Acid and Glucose
- Author : Zhenyu Dai
- Release Date : January 19, 2013
- Genre: Medical,Books,Professional & Technical,
- Pages : * pages
- Size : 11097 KB
Description
Nonenzymatic glycation has been implicated in diabetes, aging, and aging related disease such as Alzheimer’s disease. Nonenzymatic glycation has been implicated in the pathology of normal aging and diabetes. Glycation derived AGEs, especially AGE crosslinks has been hypothesized to be involved in the pathological process. Lens and collagen have been suggested to be major tissues with glycation mediated damage. In lens, ascorbic acid has been believed to be the major glycation agent instead of glucose. No quantitatively important ascorbic acid derived AGE crosslink has been unequivocally elucidated. I therefore hypothesized that the major ascorbic acid derived crosslinks remain to be characterized, which would have potential implication in the pathological process of aging and diabetic lens. On the other hand, glycation mediated crosslinks to collagen have been suggested to be linked with mechanical strength changes of extracellular matrix. I hypothesized that the interfibrillar and intrafibrillar AGE crosslinks will have different impact on mechanical strength of collagen and that detailed information on glycation derived crosslinking sites will be needed to decipher this relationship. As a simplified protein model, RNAse A was used to study the AGE crosslinking sites. In the first part of this dissertation, I isolated a novel acid-labile yellow chromophore from the incubation of lysine, histidine and D-threose. The chemical structure, a crosslink between lysine and histidine with addition of two threose molecules, was determined by one and two-dimensional NMR spectroscopy combined with LC-tandem mass spectrometry. The compound was found in lens protein incubated with threose at concentrations above 2 mM, but was not detected in the aging human lens. Histidino-threosidine is to our knowledge the first Maillard reaction product known to involve histidine in a crosslink. In the second part of this dissertation, glucosepane, a major AGE crosslink in vivo, was identified following incubation of ribonuclease A with glucose. An intra-molecular glucosepane between K41 and R39 found to be the major crosslink formed in non-oxidative physiological conditions. A minor intra-molecular glucosepane was also observed between K98 and R85. The only inter-crosslink observed between K1 and R39 was an intermolecular DODIC. To our knowledge, this is the first location of intra-molecular and inter-molecular Amadori derived crosslinks in proteins.