Abstract
Vitamin B2 primarily or secondarily participates in a much wider range of critical metabolic pathways than currently recognized. An inherited disorder of the cellular uptake and trafficking of vitamin B2 metabolites may result in poor intestinal absorption, increased urinary loss, and disrupted homeostasis of vitamin B2 metabolites in the CNS. It may affect 10%–15% of the general population and be the most prevalent genetic risk factor for several human diseases. The implications include altered metabolism of several biomolecules and enzyme systems of well-established pathophysiologic relevance such as vitamins B6, B9 (folate), B12, D3, NO, lipids, amino acids, proteins, DNA, cytochrome P-450 and other enzyme systems, HO, and homocysteine. Oxidative stress, and both apoptotic and necrotic phenomena may be enhanced. Due to the loss of the brain privilege for vitamin B2 supply, this inherited condition may be particularly relevant for CNS diseases such as migraine, brain ischemia, traumatic brain injury, neurodegenerative disorders (especially Parkinson and Alzheimer’s diseases), epilepsy, multiple sclerosis, and for Guillain-Barré syndrome, myasthenia, and mitochondrial myopathies. This chapter aims at providing an overview of the potential pathophysiologic, preventive, and therapeutic implications of this prevalent (yet poorly recognized) inherited metabolism disorder for neurological diseases.
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Abbreviations
- BBB:
-
Brain-blood barrier
- BH4:
-
Tetrahydrobiopterin
- CADCase/CSADCase:
-
Cysteine and sulfinic acid decarboxylase
- CBS:
-
Cystathionine β-synthase
- cGMP:
-
Cyclic guanosine monophosphate
- CL:
-
Cystathionine-γ-lyase, or cystathionase
- CNS:
-
Central nervous system
- CO:
-
Carbon monoxide
- CSF:
-
Cerebrospinal fluid
- EGRAC:
-
Erythrocyte glutathione reductase activation coefficient
- eNOS:
-
Endothelial nitric oxide synthase
- FAD:
-
Flavin adenine dinucleotide
- FMN:
-
Flavin mononucleotide
- GABA:
-
γ-aminobutyric acid
- GAD:
-
Glutamic acid decarboxylase
- γ-GCS:
-
γ-glutamylcysteine synthetase
- GMP:
-
Guanosine monophosphate
- GR:
-
Glutathione reductase
- GSH:
-
Reduced glutathione
- GSSG:
-
Oxidized glutathione
- GSTs:
-
Glutathione S-transferases
- H2S:
-
Hydrogen sulphide
- HO:
-
Heme oxygenase
- HPLC:
-
High-performance liquid chromatography
- iNOS:
-
Inducible nitric oxide synthase
- MADD:
-
Multiple acyl coenzyme A dehydrogenase deficiency
- MPTP:
-
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
- MS:
-
Methionine synthase
- MTHFR:
-
Methylenetetrahydrofolate reductase
- NADPH:
-
Nicotinamide adenine dinucleotide phosphate
- nNOS:
-
Neuronal nitric oxide synthase
- NO:
-
Nitric oxide
- NOS:
-
Nitric oxide synthase
- PD:
-
Parkinson’s disease
- PLP:
-
Pyridoxal-5′-phosphate
- PPO:
-
Pyridoxine(pyridoxamine)-5′-phosphate oxidase
- Rbf:
-
Riboflavin
- SHMT:
-
Hydroxymethyltransferase
- VDR:
-
Vitamin D receptor
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The authors acknowledge the support of Brazilian governmental funding agencies FAPESP, CAPES, CNPq.
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Sinigaglia-Coimbra, R., Lopes, A.C., Coimbra, C.G. (2011). Riboflavin Deficiency, Brain Function, and Health. In: Preedy, V., Watson, R., Martin, C. (eds) Handbook of Behavior, Food and Nutrition. Springer, New York, NY. https://doi.org/10.1007/978-0-387-92271-3_153
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