A hypothesis: Fructosamine-3-Kinase-Related-Protein (FN3KRP) catalyzes deglycation of Maillard intermediates directly downstream from fructosamines

Non-enzymatic glycation (a.k.a. Maillard reaction) is a series of random spontaneous reactions between reducing sugars and amines resulting in the formation of irreversible Advanced Glycation Endproducts (AGE’s). In food chemistry, this process is beneficial by contributing to flavor, aroma, texture and appearance of cooked foods. In vivo, however, Maillard reaction is deleterious because uncontrolled modification and crosslinking of biological macromolecules impairs their function. Consequently, chronic hyperglycemia of diabetes mellitus, for instance, leads to increased non-enzymatic glycation and diverse, multi-organ pathologies of diabetic complications. Based on the fact that toxic compounds, such as free radicals, are detoxified in vivo by specific defense mechanisms, one would expect to find mechanisms to control glucose toxicity as well.
Thus far only one such enzyme, Fructosamine-3-Kinase (FN3K), has been characterized. It operates intracellularly by catalyzing ATP-dependent removal of Maillard adducts, D-fructoselysines, from proteins thereby reducing the Maillard reaction flux from glucose to AGE’s When FN3K was isolated, a closely related but distinct protein copurified with it.
Unlike FN3K, however, this enzyme, Fructosamine-3-Kinase-Related Protein (FN3KRP), does not phosphorylate D-fructoselysines but it does phosphorylate several other (non-physiological) substrates. Interestingly, distribution of FN3KRP in nature appears to be nearly universal while that of FN3K is limited to endotherms. In this paper I suggest that the function of FN3KRP is deglycation of Maillard adducts downstream from fructoselysines. Such a mechanism, if proven correct, would be valuable given reports on apparent correlations between FN3KRP and some chronic conditions and/or diseases. Most recent such publication proposes that the FN3KRP gene may be a longevity gene.

Changes of Certain Metabolic and Cardiovascular Markers Fructosamine, H-FABP and Lipoprotein (a) in Patients with Hypothyroidism

Disorders of thyroid gland are common in general population, and it’s the most common affecting the endocrine system after diabetes mellitus. Thyroid function regulates a wide range of metabolic parameters, as well as affects some cardiovascular disease risk factors. Fructosamine is produced by a reaction between albumin (protein) and glucose; it is used to monitor patients with diabetes for short-term glycemic changes. H-FABP is present in the cytoplasm of cardiac myocytes, and delivers fatty acids into these cells. It has been shown to increase in myocardial injury. Lipoprotein LP(a) is consist of a special apolipoprotein called apoprotein (a), and it’s recognized as a cardiovascular disease independent risk factor.
To study whether certain metabolic and cardiovascular markers (fructosamine, H-FABP and lipoprotein (a) are changed in hypothyroid patients.
The current study included 280 overt hypothyroid, 272 with subclinical hypothyroidism compared with 270 healthy individuals of matched age and gender. For all subjects serum (TSH, T4, T3, FBS, HbA1c, fructosamine, triglycerides, cholesterol, lipoprotein (a), and Heart-type Fatty Acid-Binding Protein (H-FABP)) was measured.
Serum fructosamine level significantly elevated (p value <0.05) in patient with hypothyroidism when compared with control group, and no significant change between subclinical and control groups. There is no significant change in serum H-FABP between study subjects. There is significant increase in lipoprotein (a) in patient with hypothyroidism and those with subclinical group when compared with control group.
Serum fructosamine and level is significantly changed in patients with overt hypothyroidism when compared with euthyroid subjects. Also, we conclude that hypothyroidism increase risk of cardiovascular diseases by changing non-traditional marker such as lipoprotein (a), and no effect on H-FABP concentration.