Mathematical Modeling of Glutathione Status in Type 2 Diabetics with Vitamin B12 Deficiency

Abstract

Deficiencies in vitamin B12 and glutathione (GSH) are associated with a number of diseases including type 2 diabetes mellitus. We tested newly diagnosed Indian diabetic patients for correlation between their vitamin B12 and GSH, and found it to be weak. Here we seek to examine the theoretical dependence of GSH on vitamin B12 with a mathematical model of 1-carbon metabolism due to Reed and co-workers. We study the methionine cycle of the Reed-Nijhout model by developing a simple “stylized model” that captures its essential topology and whose kinetics are analytically tractable. The analysis shows—somewhat counter-intuitively—that the flux responsible for the homeostasis of homocysteine is, in fact, peripheral to the methionine cycle. Elevation of homocysteine arises from reduced activity of methionine synthase, a vitamin B12-dependent enzyme, however, this does not increase GSH biosynthesis. The model suggests that the lack of vitamin B12–GSH correlation is explained by suppression of activity in the trans-sulfuration pathway that limits the synthesis of cysteine and GSH from homocysteine. We hypothesize this “cysteine-block” is an essential consequence of vitamin B12 deficiency. It can be clinically relevant to appreciate that these secondary effects of vitamin B12 deficiency could be central to its pathophysiology.

The effect of vitamin B12 supplement on post‐thaw motility, viability and DNA damage of human sperm

“…In 2019 demonstrated the administration of vitamin B12 to male rats prevents the androgenic failure and counteracts the damage inflicted by cimetidine (including DNA fragmentation) upon sperm quality (Beltrame et al., 2019). Recent studies have shown that vitamin B12 modulated oxidative stress responses through the increasing methionine synthase activity related to glutathione synthesis (Karamshetty et al., 2016; Manzanares & Hardy, 2010). Glutathione synthesis is a major intracellular antioxidant which play an important functions in the intracellular protective mechanism against oxidative stress.…”

Vitamin B12 in Relation to Oxidative Stress: A Systematic Review

“…In addition, B12 may indirectly stimulate ROS scavenging by preservation of glutathione, which likely involves an intricate network of reactions that has not been fully elucidated [ 6 , 39 ].…”

Octopus arms exhibit exceptional flexibility

“…The anatomy of an octopus arm is composed almost entirely of muscle and connective tissue 27 (Fig. 1 ), minimizing mechanical constraints of physical anatomy.…”