Vitamin B12 is assimilated and transported by complex mechanisms that involve three transport proteins, intrinsic factor (IF), haptocorrin (HC) and transcobalamin (TC) and their respective membrane receptors. Vitamin deficiency is mainly due to inadequate dietary intake in vegans, and B12 malabsorption is related to digestive diseases. This review explores the physiology of vitamin B12 absorption and the mechanisms and diseases that produce malabsorption. In the stomach, B12 is released from food carrier proteins and binds to HC. The degradation of HC by pancreatic proteases and the pH change trigger the transfer of B12 to IF in the duodenum. Cubilin and amnionless are the two components of the receptor that mediates the uptake of B12 in the distal ileum. Part of liver B12 is excreted in bile, and undergoes an enterohepatic circulation. The main causes of B12 malabsorption include inherited disorders (Intrinsic factor deficiency, Imerslund-Gräsbeck disease, Addison's pernicious anemia, obesity, bariatric surgery and gastrectomies. Other causes include pancreatic insufficiency, obstructive Jaundice, tropical sprue and celiac disease, bacterial overgrowth, parasitic infestations, Zollinger-Ellison syndrome, inflammatory bowel diseases, chronic radiation enteritis of the distal ileum and short bowel. The assessment of B12 deficit is recommended in the follow-up of subjects with bariatric surgery. The genetic causes of B12 malabsorption are probably underestimated in adult cases with B12 deficit. Despite its high prevalence in the general population and in the elderly, B12 malabsorption cannot be anymore assessed by the Schilling test, pointing out the urgent need for an equivalent reliable test.
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http://dx.doi.org/10.1016/bs.vh.2022.01.016 | DOI Listing |
Biol Direct
December 2024
School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
Peroxisome proliferator-activated receptor-γ (PPARγ) is a critical regulator of adipogenesis and bone metabolism, playing complex roles in osteoporosis. This study investigates the effects of taurine and homocysteine on PPARγ, focusing on their roles in osteoclastogenesis and bone health. In-silico analyses, including molecular docking and molecular dynamic simulations, revealed that both taurine and homocysteine bind competitively to the PPARγ ligand-binding domain, exhibiting distinctive antagonistic modes, including destabilization of PPARγ's key helices H3, H4/5, H11, and H12.
View Article and Find Full Text PDFCureus
November 2024
Stroke Medicine, Dartford and Gravesham NHS Trust, London, GBR.
Vitamin B12 deficiency is a prevalent condition that can lead to serious neurological disorders, including subacute combined degeneration (SCD) of the spinal cord, which can result in lasting damage if not promptly treated. This report discusses a unique case of a 53-year-old female patient who presented with a one-week history of gait instability and falls, ultimately diagnosed with SCD due to severe vitamin B12 deficiency. Notably, the patient exhibited an atypical presentation, lacking classic symptoms such as paraesthesia and hematologic abnormalities, which often accompany B12 deficiency.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Biomolecular Diagnostic Laboratories, Via N. Porpora, 50144 Florence, Italy.
Hyperhomocysteinemia (HHcy) is a medical condition characterized by an abnormally high level of homocysteine (Hcy) in the blood. Homocysteine is a toxic sulfur-containing amino acid that is produced during the metabolism of methionine. Under normal circumstances, Hcy is recycled back to methionine via the remethylation pathway, through the action of various enzymes and vitamins, particularly folic acid (vitamin B9) and B12 used when intracellular methionine levels are low, thus restoring the necessary levels to correctly maintain active protein synthesis.
View Article and Find Full Text PDFBMC Cardiovasc Disord
November 2024
Department of Cardiology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
Background: Cardiovascular disease (CVD) is a major global health concern with increasing incident cases and deaths. Homocysteine (Hcy) has been investigated for its potential association with CVD, researchers have debated the extent to which Hcy should be considered a risk factor for cardiovascular diseases, as only 50% of CVD can be explained by classical risk factors.
Methods: We conducted a prospective cohort study using NHANES 1999-2006 data, analyzing 1,739 US patients aged at least 30 with CVD.
Biomolecules
September 2024
Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, 41100 Larissa, Greece.
While there is a link between homocysteine (Hcy), B12 and folic acid and neurodegeneration, especially in disorders like Parkinson's and Alzheimer's diseases, its role in Parkinson plus syndromes (PPS) has only been partially investigated. It appears that elevated Hcy, along with an imbalance of its essential vitamin cofactors, are both implicated in the development and progression of parkinsonian syndromes, which represent different disease pathologies, namely alpha-synucleinopathies and tauopathies. Attributing a potential pathogenetic role in hyperhomocysteinemia would be crucial in terms of improving the diagnostic and prognostic accuracy of these syndromes and also for providing a new target for possible therapeutic intervention.
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