PMID- 21924559
OWN - NLM
STAT- MEDLINE
DCOM- 20120201
LR  - 20131121
IS  - 1532-2777 (Electronic)
IS  - 0306-9877 (Linking)
VI  - 77
IP  - 5
DP  - 2011 Nov
TI  - The physiological substrates of fructosamine-3-kinase-related-protein (FN3KRP) 
      are intermediates of nonenzymatic reactions between biological amines and ketose 
      sugars (fructation products).
PG  - 739-44
LID - 10.1016/j.mehy.2011.07.027 [doi]
AB  - The physiological function of fructosamine-3-kinase (FN3K) is relatively well 
      understood. As shown in several studies, most conclusively by data on the FN3K-KO 
      mouse, this enzyme breaks down compounds produced by the non-enzymatic glycation 
      of proteins by D-glucose. In contrast with FN3K, very little is known about the 
      function of the fructosamine-3-kinase-related-protein (FN3KRP) even though it has 
      a 65% amino-acid sequence identity with FN3K. We do know that this enzyme is a 
      kinase as evidenced by its ability to phosphorylate non-physiological compounds 
      such a psicosamines, ribulosamines, erythrulosamines, and glucitolamines. 
      However, FN3KRP does not phosphorylate any of the numerous Amadori products that 
      are the physiological substrates of FN3K. The fact that FN3KRP is highly 
      conserved in all vertebrates and present throughout nature suggests that it plays 
      an important role in cellular metabolism and makes identification of its 
      physiological substrates an important objective. In this paper, we propose that 
      FN3KRP phosphorylates products resulting from a non-enzymatic glycation of amines 
      by ketoses (fructation) that involves a 2,3-enolization and produces the stable 
      Amadori intermediate, 2-amino-2-deoxy-D-ribo-hex-3-ulose (ADRH). This ketosamine 
      is then phosphorylated to 2-amino-2-deoxy-D-ribo-hex-3-ulose-4-phosphate 
      (ADRH-4-P). Since phosphates are much better leaving groups than hydroxyls, this 
      destabilizes the C-2 amine bond and results in a spontaneous beta-elimination of the 
      phosphate to regenerate an unmodified amine with the concomitant production of 
      4-deoxy-2,3-diulose. Consequently, we postulate that the principal physiological 
      function of FN3KRP is the breakdown of nonenzymatic fructation products. If 
      confirmed in future studies, this hypothesis opens up new perspectives for an 
      improved understanding of biological Maillard reactions and mechanisms for their 
      control and/or reversal.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Szwergold, Benjamin S
AU  - Szwergold BS
AD  - Dartmouth Medical School, Hanover, NH, USA. szwerg115@gmail.edu
FAU - Bunker, Richard D
AU  - Bunker RD
FAU - Loomes, Kerry M
AU  - Loomes KM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110915
PL  - United States
TA  - Med Hypotheses
JT  - Medical hypotheses
JID - 7505668
RN  - 0 (Amines)
RN  - 0 (Ketones)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.- (fructosamine-3-kinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Amines/*metabolism
MH  - *Carbohydrate Metabolism
MH  - Glucose/metabolism
MH  - Ketones/*metabolism
MH  - Models, Molecular
MH  - Phosphorylation
MH  - Phosphotransferases (Alcohol Group Acceptor)/*metabolism
MH  - Substrate Specificity
EDAT- 2011/09/20 06:00
MHDA- 2012/02/02 06:00
CRDT- 2011/09/20 06:00
PHST- 2011/03/12 00:00 [received]
PHST- 2011/07/12 00:00 [revised]
PHST- 2011/07/13 00:00 [accepted]
PHST- 2011/09/20 06:00 [entrez]
PHST- 2011/09/20 06:00 [pubmed]
PHST- 2012/02/02 06:00 [medline]
AID - S0306-9877(11)00345-8 [pii]
AID - 10.1016/j.mehy.2011.07.027 [doi]
PST - ppublish
SO  - Med Hypotheses. 2011 Nov;77(5):739-44. doi: 10.1016/j.mehy.2011.07.027. Epub 2011 
      Sep 15.