Maillard reaction of ribose 5-phosphate generates superoxide and glycation products for bovine heart cytochrome c reduction

Abstract

Ribose 5-phosphate (R5P) is a sugar known to undergo the Maillard reaction (glycation) at a rapid rate. In a reaction with the lysines of bovine heart cytochrome c, R5P generates superoxide (O 2 -) that subsequently reduces ferri-cytochrome c to ferro-cytochrome c. The rate equation for the observed cytochrome c reduction is first order in respect to cytochrome c and half order in respect to R5P. The addition of amines to the cytochrome c-R5P system greatly increases the O 2 -generation with rates of approximately 1.0 μM min -1 being observed with millimolar levels of R5P and amine at 37 °C. Pre-incubation of R5P with the amine prior to cytochrome c addition further enhances the rate of cytochrome c reduction approximately 2-fold for every 30 minutes of incubation. While clearly accounting for a portion of the reduction of cytochrome c, O 2 -is not the sole reductant of the system as the use of superoxide dismutase only partially limits cytochrome c reduction, and the contribution of O 2 -proportionally decreases with longer amine-R5P incubation times. The remainder of the cytochrome c reduction is attributed to either the Amadori product or a cross-linked Schiff base created when a Maillard reaction-derived dicarbonyl compound(s) reacts with the amine. It is believed these compounds directly transfer electrons to ferricytochrome c and subsequently become stable free-radical cations. ATP, a putative regulator of cytochrome c activity, does not inhibit electron transport from O 2 -or the cross-linked Schiff base but does prevent R5P from reacting with surface lysines to generate superoxide. The spontaneous reaction between R5P and amines could serve as an alternative system for generating O 2 -in solution.

Overlapped Metabolic and Therapeutic Links between Alzheimer and Diabetes

“…In glucose autoxidation, glucose forms enediol radicals and is converted to reactive ketoaldehydes and superoxide; consequently hydroxyl radicals are produced in presence of transition metals via H 2 O 2 if not degraded by catalase or glutathione peroxidase [248,249]. Hyperglycemia drives the inner mitochondrial membrane potential upward through generation of excessive electron donors in the Kreb's cycle [250].…”

Ribose sugars generate internal glycation cross-links in horse heart myoglobin

“…The rate of these and other glycation reactions depends on the nature of the sugar (high acyclic form is favorable) and the amine (low pK a is favorable). In a reaction between ribose 5-phosphate (R5P, 10 mM) and the amines contained in cytochrome c (82 μM), O 2 − was generated at a rate of approximately 50 μM min −1 [10]. O 2 − can subsequently reduce ferricytochrome c to ferrocytochrome c [10].…”

“…In a reaction between ribose 5-phosphate (R5P, 10 mM) and the amines contained in cytochrome c (82 μM), O 2 − was generated at a rate of approximately 50 μM min −1 [10]. O 2 − can subsequently reduce ferricytochrome c to ferrocytochrome c [10]. Similarly, glycation of myoglobin with fructose [11] or with R5P (see below) creates superoxide that can lead to reduction of metmyoglobin to oxyferromyoglobin.…”

Ribose 5-Phosphate Glycation Reduces CytochromecRespiratory Activity and Membrane Affinity

“…Previously, we have shown that R5P at millimolar levels can rapidly reduce ferri-cyt c, generating O 2 − in the process (18). The observation that the reduction rate can be slowed by ATP suggests that a primary site of interaction of R5P on cyt c is at this site or at least involves some of the ATP-interacting residues including Lys86, Lys87, Lys88, Arg91 or perhaps Lys72 and Lys73.…”