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, 2019 (1), 221-231
eCollection

Glut-1 Explains the Evolutionary Advantage of the Loss of Endogenous Vitamin C-synthesis: The Electron Transfer Hypothesis

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Glut-1 Explains the Evolutionary Advantage of the Loss of Endogenous Vitamin C-synthesis: The Electron Transfer Hypothesis

Tabea C Hornung et al. Evol Med Public Health.

Abstract

Introduction: During evolution, some species including humans, monkeys and fruit bats lost the ability for ascorbic acid (AA) biosynthesis due to inactivation of the enzyme l-gulono-lactone oxidase (GLO) and subsequently became dependent on dietary vitamin C. There are four current hypotheses in relation to the benefit of vitamin C dependence in the context of adaptation and reproduction. Here we advance and test a new 'electron transfer hypothesis', which focusses on the role of the expression of glucose transporter 1 (Glut-1) in red blood cells (RBCs) in recycling vitamin C, thereby increasing the efficiency of micronutrient uptake.

Methods: To evaluate the benefit of Glut-1 expression, we determined vitamin C uptake into RBCs and potential release from two different species, humans with l-Gulono-lactone-oxidase (GLO-loss) and pigs with functional GLO.

Results: The oxidized form of vitamin C (dehydroascorbate, DHA) was transported into human RBCs via Glut-1. There was no transport of either the reduced (AA) or the oxidized vitamin in pig erythrocytes.

Conclusion: We propose that the transport of vitamin C increases an intracellular electron pool, which transfers electrons from intracellular ascorbate to extracellular substances like ascorbyl free radical or DHA, resulting in 100-fold smaller daily requirement of this essential redox sensitive micronutrient. This would be an advantage during seasonal changes of the availability from food and may be the key for the survival of individuals without vitamin C biosynthesis.

Lay summary: 40 million years ago some individuals lost the ability to synthesize vitamin C. Why did they survive such as humans until now? Individuals with a specific glucose transporter Glut-1 on their erythrocytes which transports vitamin C need less and are protected from scarcity due to seasons and food competitors.

Keywords: glucose transporter; gulono-lactone-oxidase; vitamin C; vitamin C recycling.

Figures

Figure 1.
Figure 1.
Schematic presentation of different glucose-transporters and their special features
Figure 2.
Figure 2.
Intracellular ascorbate accumulation in human RBCs (n = 6) was determined over a period of 120 min. Cells were incubated in PBS containing 3 (circle), 5 (square) or 25 (triangle) mM glucose and 100 μM ascorbate (A) or 100 μM ascorbate with 5 mU ascorbate oxidase (B)
Figure 3.
Figure 3.
Intracellular ascorbate accumulation in pigs (n = 4) was determined over a period of 120 min. Cells were incubated in PBS containing 3 (circle), 5 (square) or 25 (triangle) mM glucose and 100 μM ascorbate (A) or 100 μM ascorbate with 5 mU ascorbate oxidase (B)
Figure 4.
Figure 4.
Intracellular ascorbate concentration of RBCs from six healthy volunteers that were separated by age before was corrected to the haemoglobin content. Significant differences (P < 0.05) of intracellular ascorbate concentration are denoted by asterisks
Figure 5.
Figure 5.
RBCs from three different volunteers were isolated and incubated in PBS containing 5 mM glucose, 100 μM ascorbate and with (black square) or without (grey square) ascorbate oxidase. After incubation for 2 h, cells were washed and transferred into PBS without vitamin C. Extracellular vitamin C accumulation (disposal from RBCs) was determined by HPLC analysis. Significant differences (P < 0.05) of ascorbate disposal are marked by asterisks
Figure 6.
Figure 6.
Oxidative stress and reactive oxygen species and radicals increase the production of ascorbate free radical (AfR) and DHA. DHA is transported by Glut-1/stomatin complex into RBCs where it is intracellularly reduced to AA. This electron pool is used to reduce extracellular AfR molecules and to prevent further production of DHA. The bigger the intracellular electron pool, the more effective is the recycling of extracellular vitamin C due to the independence of this pool from direct glucose uptake and hexose monophosphate pathway
Figure 7.
Figure 7.
Comparison of the three different ways glucose can be metabolized: (1) Via anaerobe glycolysis: 6 energy equivalents (ATP) are produced. (2) Via the hexose monophosphate pathway (HMP): 5 Energy and 6 reduction equivalents are generated. (3) The ascorbate synthesis produces 2 AA from 3 glucose molecules, one glucose molecule is needed for ATP production (glycolysis) to activate the remaining two glucose molecules.

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