Vitamin B12, also known as cobalamin, is an essential water-soluble vitamin that plays critical roles in DNA synthesis, fatty acid and amino acid metabolism, and nerve cell function. It is naturally found in animal products and produced by bacteria. Deficiency can result in megaloblastic anemia and neurological problems. While generally safe, high doses may cause side effects like diarrhea or allergic reactions. Vitamin B12 has various applications in treating conditions like immune dysfunction, allergies, and cyanide poisoning.
Vitamin B12- Chemistry, functions and clinical significanceNamrata Chhabra
Vitamin B12- Chemical structure, Forms of B12, Sources, absorption, storage, transportation, metabolic role, deficiency, megaloblastic anemia and neurological changes, laboratory diagnosis and treatment
VITAMIN B1 [THIAMINE] MEDICINAL CHEMISTRY BY P. RAVISANKAR [ SOURCE, STRUCTUR...Dr. Ravi Sankar
VITAMIN B1 [THIAMINE] MEDICINAL CHEMISTRY BY P. RAVISANKAR [ SOURCE, STRUCTURES AND CHEMISTRY OF VITAMIN B1, HYSTORY OF VITAMIN B1, SOURCES OF VITAMIN B1, RDA, PHYSIOLOGICAL IMPORTANCE(ROLE) OF VITAMIN B1, SYNTHESIS OF VITAMIN B1, OXIDATION OF THIAMINE TO THIOCROME, THERAPEUTIC USES ,DEFICIENCY OF VITAMIN B1.
BY P.RAVISANKAR
VIGNAN PHARMACY COLLEGE, VADLAMUDI, GUNTUR, A.P, INDIA.
Vitamin B12- definition, functions, absorption, storage, transportation, deficiency, pernicious anemia, relationship between vitamin B12 and folate deficiency, sign & symptoms, deficiency in case of maternal & child health care, RDA, sources, prevention and treatment.
Vitamin B12- Chemistry, functions and clinical significanceNamrata Chhabra
Vitamin B12- Chemical structure, Forms of B12, Sources, absorption, storage, transportation, metabolic role, deficiency, megaloblastic anemia and neurological changes, laboratory diagnosis and treatment
VITAMIN B1 [THIAMINE] MEDICINAL CHEMISTRY BY P. RAVISANKAR [ SOURCE, STRUCTUR...Dr. Ravi Sankar
VITAMIN B1 [THIAMINE] MEDICINAL CHEMISTRY BY P. RAVISANKAR [ SOURCE, STRUCTURES AND CHEMISTRY OF VITAMIN B1, HYSTORY OF VITAMIN B1, SOURCES OF VITAMIN B1, RDA, PHYSIOLOGICAL IMPORTANCE(ROLE) OF VITAMIN B1, SYNTHESIS OF VITAMIN B1, OXIDATION OF THIAMINE TO THIOCROME, THERAPEUTIC USES ,DEFICIENCY OF VITAMIN B1.
BY P.RAVISANKAR
VIGNAN PHARMACY COLLEGE, VADLAMUDI, GUNTUR, A.P, INDIA.
Vitamin B12- definition, functions, absorption, storage, transportation, deficiency, pernicious anemia, relationship between vitamin B12 and folate deficiency, sign & symptoms, deficiency in case of maternal & child health care, RDA, sources, prevention and treatment.
VITAMINB2[RIBOFLAVIN] MEDICINAL CHEMISTRY,BY P.RAVISANKAR [SOURCES OF VITAMI...Dr. Ravi Sankar
VITAMINB2[RIBOFLAVIN] MEDICINAL CHEMISTRY,BY P.RAVISANKAR [SOURCES OF VITAMIN B2,CHEMISTRY OF VITAMIN B2,PHYSIOLOGICAL IMPORTANCE,SYNTHESIS OF RIBOFLAVIN,REACTIONS, VITAMIN B2 DEFICIENCY SYMPTOMS,FUNCTIONS,USES OF RIBOFLAVIN.
BY P.RAVISANKAR,VIGNAN PHARMACY COLLEGE, VADLAMUDI, GUNTUR, ANDHRA PRADESH, INDIA.
this presentation is about Vitamin B6 which include structure , biochemical function , biochemical reaction, effect of deficiency of vitamin B6, Toxicity and function of Vitamin B6.
Thiamine is also called as vitamin B1, Aneurine (it can relieve neuritis), or antiberberi
factor.
• In 1900, Christian Eijkman produced beriberi in chicken by feeding polished rice (Nobel
Prize, 1929).
• Adolf Windaus (Nobel Prize, 1928) elucidated the structure of the vitamin.
Structure of Thiamine:
Biosynthesis:
Deficiency Manifestations of Thiamine
Thiamine, also known as thiamin or vitamin B₁, is a vitamin found in food and manufactured as a dietary supplement and medication. Food sources of thiamine include whole grains, legumes, and some meats and fish
B12 metabolism..................................... and role of various proteins in b12 metabolism..... necessity of supplementation..........................................
Folic acid- Chemistry, One carbon metabolism and megaloblastic anemiaNamrata Chhabra
Folic acid- Structure, forms, absorption, transportation, storage, excretion, role in one-carbon metabolism, role in methionine synthesis, role in nucleotide biosynthesis, folate trap, folate antagonists, megaloblastic anemia
VITAMINB2[RIBOFLAVIN] MEDICINAL CHEMISTRY,BY P.RAVISANKAR [SOURCES OF VITAMI...Dr. Ravi Sankar
VITAMINB2[RIBOFLAVIN] MEDICINAL CHEMISTRY,BY P.RAVISANKAR [SOURCES OF VITAMIN B2,CHEMISTRY OF VITAMIN B2,PHYSIOLOGICAL IMPORTANCE,SYNTHESIS OF RIBOFLAVIN,REACTIONS, VITAMIN B2 DEFICIENCY SYMPTOMS,FUNCTIONS,USES OF RIBOFLAVIN.
BY P.RAVISANKAR,VIGNAN PHARMACY COLLEGE, VADLAMUDI, GUNTUR, ANDHRA PRADESH, INDIA.
this presentation is about Vitamin B6 which include structure , biochemical function , biochemical reaction, effect of deficiency of vitamin B6, Toxicity and function of Vitamin B6.
Thiamine is also called as vitamin B1, Aneurine (it can relieve neuritis), or antiberberi
factor.
• In 1900, Christian Eijkman produced beriberi in chicken by feeding polished rice (Nobel
Prize, 1929).
• Adolf Windaus (Nobel Prize, 1928) elucidated the structure of the vitamin.
Structure of Thiamine:
Biosynthesis:
Deficiency Manifestations of Thiamine
Thiamine, also known as thiamin or vitamin B₁, is a vitamin found in food and manufactured as a dietary supplement and medication. Food sources of thiamine include whole grains, legumes, and some meats and fish
B12 metabolism..................................... and role of various proteins in b12 metabolism..... necessity of supplementation..........................................
Folic acid- Chemistry, One carbon metabolism and megaloblastic anemiaNamrata Chhabra
Folic acid- Structure, forms, absorption, transportation, storage, excretion, role in one-carbon metabolism, role in methionine synthesis, role in nucleotide biosynthesis, folate trap, folate antagonists, megaloblastic anemia
The first free on-line Journal for Cactus and Succulent Enthusiasts. Number 16, published on June 2016.
New In this edition:
-Nopalxochia conzattiana
-Pilosocereus gounellei
-High Altitude Cacti
-(Steno)Cereus pseudosonorensis
-A New Taxon of Rebutia
-Copiapoa fusca and Copiapoa corralensis
-Travel with the Cactus Expert
-Duchesne County, Utah (USA).
The first free on-line Journal for Cactus and Succulent Enthusiasts. February 2016.
In this edition:
1 Sclerocactus parviflorus
2 Inquisivi, Bolivia
3 Sedum morganianum
2 Inquisivi, Bolivia
4 Gymnocalycium
5 Sulcorebutia
Cobalamin is also called vitamin b12.
Group of compounds called corrinoids (a group of cobalamin)- Coenzyme form: methylcobalamin and 5-deoxyadenosylcobalamin are forms of vitamin B12 in the human body- Humans can convert most of the other cobalamins into an active coenzyme form.
Once absorbed, cobalamin travels in the portal blood to the liver, and then to the rest ofthe body, bound to the transport protein, transcobalamin
Methionine synthase- converts homocysteine to methionine. Reduces blood homocysteine concentrations (reduces CVD).
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
2. Outline
Vitamins; Vit B-12 structure
Sources
Biological Glance
Vitmain B-12 deficiencies and clinical
implications.
Applications
Side effects
3. Vitamins- general concepts
•
What are vitamins?
Any group of organic compounds that either our own bodies
cannot synthesize them, or they are not synthesized in amounts
sufficient for our needs. Thus we must obtain them from the
foods we eat, or via vitamin supplements. 1
•
What is the difference between fat-soluble and water-soluble
vitamins?
- Fat-soluble vitamins are stored in the liver and fatty tissues.
These are not readily excreted from the body such as vitamin A,
vitamin D, vitamin E and vitamin K.
- Water-soluble vitamins travel in the blood and are stored in
limited amounts. These are readily excreted from the body
through urine such as, Vit C, Vit B12, thiamin, niacin, riboflavin,
tryptophan, pantothenic acid, biotin, and folic acid.
4. Vit B12 (cobalamin)
Is
a complex biochemical structure, but is water soluble.
Vitamin B12 is generic name for group of compounds called
corrinoids (four pyrrole rings).
◦ corrin nucleus
◦ atom of cobalt in center
◦ attached are one of following
CN = cyanocobalamin (CNCbl)
OH=hydroxocobalamin (OHCbl)
5’-adenosyl=adenosylcobalamin*(AdoCbl)
-CH3=methylcobalamin* (MeCbl)
7. Sources
•
•
•
•
Seldom found in foods from plants
Synthesis is limited to bacteria. Rumen microbial
synthesis depends on the supply of cobalt in the diet
Animal products
▫ Derive their cobalamin from micro-organisms; Animal derived
foods are a primary source since animals eat another animal food,
they produces B12 internally due to the intestinal bacteria (not
present in humans), and they eat food contaminated with
bacteria.
▫ Meat, poultry, fish, shellfish, eggs, milk, milk products
▫ Liver is a good source
• Supplements
Cyanocobalamin and hydroxycobalamin
8. B12 (Biological Glance)
Metabolizing fats and proteins. For example, it is important
for amino acid incorporation; like Methionine (Sulfur
containing amino acids.
1-Carbon Transfer. For Example, it is important for the
sythesis of folate (vitamin B9; folic acid) and of methionine.
Proper nerve function
production of red blood cells.
DNA reproduction
9. Odd-Chain Fatty acids Catabolism
Figure 3: The The oxidation of a fatty acid containing an odd number of carbon
atoms.
16. Pernicious Anemia
• Is the classic term used to describe the megaloblastic anemia which
develops as a result of autoimmune destruction of the gastric
mucosa (atrophic gastritis) and autoantibodies directed against
intrinsic factor which is needed for the absorption of B12 in our
bodies and is mainly secreted from gastric parietal cells.
• This type of anemia lacks the B12 which coplues with the folate to
produce red blood cells. Otherwise, your red blood cells don't
divide normally and are too large. They may have trouble getting
out of the bone marrow—a sponge-like tissue inside the bones
where blood cells are made.
17.
18.
19. Synthesis of dTMP from dUMP
The salvage pathway to dTTP synthesis involves the enzyme
thymidine kinase which can us either thymidine or deoxyuridine as
substrate:
thymidine + ATP <——> TMP + ADP
deoxyuridine + ATP <——> dUMP + ADP
The activity of thymidine kinase (one of the various
deoxyribonucleotide kinases) is unique in that it fluctuates with the
cell cycle, rising to peak activity during the phase of DNA synthesis;
it is inhibited by dTTP.
20. Alzheimer &Memory loss
(fact or fiction)
The
possible link is that Vit.B12 effectively help in keeping &
controlling the levels of homocysteine in our bodies. Normally
we don’t have much of this because it is quickly turned into
two important brain chemicals, including acetylcholine, which
is essential for laying down memories.
There
have been lots of studies showing that Alzheimer’s
patients have unusually high levels of homocysteine in their
bloodstream. They also have low levels of acetylcholine 3
22. The biosynthesis of cysteine in animals. (A
stands for acceptor.)
Fig. 23-16, p.642
23.
24. Peripheral Neuropathy
•
Damage to one or more of the peripheral nerves in the body.
The damage means that the messages that travel between the
central and peripheral nervous system are disrupted. There
are many different conditions that can lead to peripheral
neuropathy.
•
Interestingly, diabetes is the most common cause of persistent
(chronic) peripheral neuropathy. (What’s the link with B12??)
•
Noteworthy, peripheral neuropathy is typically diagnosed as
diabetic neuropathy, but this can also be a symptom of vitamin
B12 deficiency! 4
25. Metformin induce B12 Deficiency
•
Common, potentially damaging, and well-documented
complication of metformin (popular diabetes drug) is vitamin
B12 malabsorption which is poorly recognized and not
screened for or treated prophylactically by the majority of
physicians who prescribe metformin.
•
Interestingly the clinical presentation of the neuropathic
symptoms and clinical findings could be easily misdiagnosed as
being due to diabetic neuropathy, which would have further
prolonged the time to diagnosis and treatment of the
neuropathy and resulted in further neurological damage. 4
26. Hot topics- Vit B12 applications!
•
It has been suggested that B12 has a vital role in regulating the
immune system response, more specifically the cellular mediated
immunity. In a study conducted in Gunma University School of
Medicine, Japan in 1999 of 11 patients with B12 deficiency, the
lymphocyte subpopulations and NK cell activity were evaluated.
•
The findings of this study has shown a considerable decrease in the
total number of CD8+ cells and suppressed NK cell activity in vit.B12deficient patients Wherein, these abnormalities could be at least
partly restored by methyl-B12 treatment. Moreover, augmentation
of CD8+ cells by methyl-B12 treatment was observed even in control
subjects 5
27.
28. Vitamin B12 in IgE-mediated Allergic
Reactions
The mechanism of action for Vitamin B12 in IgE-mediated
allergic diseases, such as allergic rhinitis and asthma, may
involve the maturation of certain immune system cells including
polynucleated cells, natural killer (NK) cells, and CD8 cells.
These immune system cells may require a sustained and
elevated serum Vitamin B12 concentration to develop from an
immature state to a mature state in which they can exert their
down-regulatory function on the immune system.
Polynucleated cells are known to have memories that last many
years, a concept consistent with controlled studies
demonstrating reductions in symptoms and in specific IgE levels
persisting many months after parenteral Vitamin
B12 treatment.
29. Vit B12 and Cyanide poisoning
Vitamin
B-12 has the largest and most complex chemical
structure of all vitamins. On the same note, vitamin B-12 is
the only vitamin that contains a metal, a cobalt(II) ion bonded
to a porphyrin-like- chelating agent.
How
does it work in treating Cyanide Toxicity?
Hydroxocobalamin combines with cyanide to form
cyanocobalamin (vitamin B-12), which is renally cleared.
30. Double faces! (B-12 as a Villain)
Most B-12 circulating in the blood is in the methylcobalamin
form. Before the body can use the cyanocobalamin form, it
must be converted by the liver to methylcobalamin.
Dark side of the industry?
The history of vitamin B-12 and the switch from the methyl
to the cyanide form of B-12 is the result of using charcoal to
filter extracts during the isolation of B-12. Cyanide in
charcoal rapidly converts all natural forms of B-12 into the
cheaper "more stable" (but NOT better) cyanide form.
Because of this fact, the discovery of B-12 coenzymes and
their life-altering metabolic role was delayed for years. Once
again, Big Money and sloppy science are helping destroy our
health.
31. Side Effects?
Vitamin
B12 is LIKELY SAFE for most people when
taken by mouth or when the prescription-only,
injectable product is used correctly.
In some people, vitamin B12 might cause diarrhea,
blood clots, itching, serious allergic reactions, and other
side effects.
32. References
1- Campbell M. K., Farrell S. O. (2009). Belmont, USA , Cengage Learning.
2- Toh B.-H., et al (1997). Pernicious Anemia, New England Journal of Medicine.
337:1441-1448.
3- A. D. Smith S.M., et al. (2010). Homocysteine-Lowering by B Vitamins Slows the
Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized
Controlled Trial. PLoS ONE 5(9).
4- Callaghan B. C., Hur J., and Feldman E.L. (2012)Diabetic Neuropathy, Current
Opinion in Neurology. 25(5):536-541.
5- Tamura, et al. Immunomodulation by vitamin B12: augmentation of CD8+ T (1999)
lymphocytes and natural killer (NK) cell activity in vitamin B12-deficient patients by
methyl-B12 treatmentClinical and Experimental Immunology. Clinical and
Experimental Immunol. 116(1)28-32
35. History
1822: J.S. Combe described pernicious anemia.
1926: Minot and Murphy, treatment in lightly cooked
liver
1928: W.B. Castle, intrinsic factor
1940s: Combs and Norris, close to isolation
1948: Isolation in USA and UK
1955: Elucidation of chemical structure
1970: de novo synthesis
Editor's Notes
Cobalamin enzymes catalyze 3 types of reactions: intramolecular rearrangements, methylations, and the reduction of ribonucleotides to deoxyribonucleotides. The two reactions in mammals that require coenzyme B12 are: (1) the conversion of L-methylmalonyl CoA into succinyl CoA and (2) methylation of homocysteine to form methionine. Reaction (2) is particularly important as Met is necessary for the generation of coenxymes that play a role in the synthesis of purines and thymine. The basic structure of a cobalamin is pictured: the core consists of a corrin ring with a central cobalt atom.
Write this down, as this is not mentioned in the slides:
In mammals, cobalamin is a cofactor for only two enzymes, methionine synthase and L-methylmalonyl-CoA mutase.
Vitamin B 12 contains a cobalt metal ion bound to a porphyrin ring. Cobalt normally forms six coordinate bonds. Besides the four bonds to the nitrogens of the porphyrin, one bond is to a ring nitrogen of dimethylbenzamidine. The final bond is to a cyanide ion in the vitamin, or to the 5′ carbon of adenosine in the active coenzyme
itamin B12 is a substance whose biochemistry is complex. Basically it consists of a cobalt-containing porphyrin-like prosthetic group attached to a nucleotide (cobalt is a major trace metal in human physiology, with the average body containing 1.1 grams of the element, third in abundance after iron and zinc). The diagram at left shows the structure of cyanocobalamin, one the simpler forms of the vitamin. B12 has been called the most complicated molecule in the human body that is not simply a repeating chain of smaller units (like proteins and nucleic acids). The laboratory synthesis of this substance, not accomplished until 1971, capped off the distinguished career of Nobel-winning organosynthesist Robert Burns Woodward.
B12 is synthesised in nature by micro-organisms. Animal-derived foods are a primary source because animals eat other animal food, they produce B12 internally due to the intestinal bacteria (not present in humans), and they eat food contaminated with bacteria.
Please keep those in mind while we discuss B12 deficiencies:
In humans, B12 exerts its physiologic effects on two major enzymatic pathways.
First, methyl-cobalamin (m-B12) is a cofactor in the conversion of
Homocysteine to Methionine . This reaction is essential for the conversion of
dietary and storage ( methyltetrahydrofolate ) folates to tetrahydrofolate .
Second, adenosyl-cobalamin (aB12) is a cofactor in the conversion of
Methylmalonyl coenzyme A ( MMCoA ) to Succinyl-CoA .
http://www.fao.org/docrep/004/Y2809E/y2809e0b.htm
anemia
nerve damage
Whose at risk
pernicious anemia
B-12 injections often taken regularly
HIV
Chronic Fatigue Syndrome
Unsaturated and Odd-Chain Fatty Acids Require Additional Steps for Degradation
Most fatty acids have an even number of carbon atoms due to the process by which they were synthesized, thus the beta-oxidation pathway can successfully complete the degradation of these molecules. However, there are more steps required for fatty acid chains that are not as simple, i.e. those that are unsaturated or which have an odd number of carbons.
Vitamin B12 contains a cobalt atom and a corrin ring[edit]
Cobalamin
Cobalamin enzymes catalyze 3 types of reactions: intramolecular rearrangements, methylations, and the reduction of ribonucleotides to deoxyribonucleotides. The two reactions in mammals that require coenzyme B12 are: (1) the conversion of L-methylmalonyl CoA into succinyl CoA and (2) methylation of homocysteine to form methionine. Reaction (2) is particularly important as Met is necessary for the generation of coenxymes that play a role in the synthesis of purines and thymine. The basic structure of a cobalamin is pictured: the core consists of a corrin ring with a central cobalt atom.
During this rearragement, two groups attached to adjacent carbon atoms are excahnged, the process being catalyzed by coenzyme B12. The first step in these rearrangements is the carbon-cobalt bond of 5’-deoxyadenosyl being cleaved (a homolytic cleavage reaction). This creates the Co2+ coenzyme form and a radical of 5’-deoxyadenosyl (pictured).
Vitamin B 12 activates methyl groups for methionine biosynthesis by binding them to the Co ion at the sixth position. The methyl group donor to B 12 is 5‐methyl tetrahydrofolate. The methyl‐B 12 donates its methyl group to homocysteine,forming methionine. Besides being incorporated into proteins, methionine is the source of methyl groups for several important reactions, including the modification of cellular RNAs and the biosynthesis of lipids
Figure taken from http://www.cliffsnotes.com/sciences/biology/biochemistry-ii/amino-acid-metabolism-carbon/1-carbon-metabolism
N5-METHYL-THF IS A STORAGE FORM OF FOLATE. THE REACTION REDUCTION OF N5,10-METHYLENE THF TO N5-METHYL-THF IS IRREVERSIBLE. TO GET THE FOLATE OUT OF STORAGE, B12 MUST CATALYZE THE CONVERSION OF HOMOCYSTEINE TO METHIONINE, RESULTING IN THE PRODUCTION OF THF FROM N5-METHYL THF.
People with a folate deficiency can experience side effects relating to the fact that folate is needed for TMP production in dividing cells. They can present with anemia, hair loss, GI symptoms, etc. In fact, some cancer drugs exploit this and there are chemotherapeutic agents that target both dihydrofolate reductase and thymidylate synthase. Sometimes people are treated with supplemental folate for what is thought to be a folate deficiency, and they actually had a B12 deficiency. These people can experience certain neurological symptoms after they had experienced an initial relief in their folate deficiency symptoms. This phenomenon occurs because B12 impairs the ability to take the folate out of its ‘storage’ as the 5-methyl THF.
ype “vitamin B-12” into your favorite Internet search engine, and you’ll find an array of information and advertising sites touting various vague health benefits, including the “amazing” exercise-boosting ability of this complex compound. Despite its popularity as a general “energizer” for the body, mind and spirit, the evidence that vitamin B-12 should be taken either orally or parenterally by individuals who do not have a clinical diagnosis of deficiency is generally not convincing
A recent study also suggests that high vitamin B12 status may be associated with better treatment outcome. Folate and vitamin B12 are major determinants of one-carbon metabolism, in which S-adenosylmethionine (SAM) is formed. SAM donates methyl groups that are crucial for neurological function. Increased plasma homocysteine is a functional marker of both folate and vitamin B12 deficiency. Increased homocysteine levels are found in depressive patients. In a large population study from Norway increased plasma homocysteine was associated with increased risk of depression but not anxiety. There is now substantial evidence of a common decrease in serum/red blood cell folate, serum vitamin B12 and an increase in plasma homocysteine in depression. Furthermore, the MTHFR C677T polymorphism that impairs the homocysteine metabolism is shown to be overrepresented among depressive patients, which strengthens the association. On the basis of current data, we suggest that oral doses of both folic acid (800 microg daily) and vitamin B12 (1 mg daily) should be tried to improve treatment outcome in depression.
is the classic term used to describe the megaloblastic anemia which develops as a result of autoimmune destruction of the gastric mucosa (atrophic gastritis) and autoantibodies directed against intrinsic factor. PA is said to occur most commonly in elderly Caucasians of northern European extraction and in younger African-Americans
methionine synthase activity slows down, reducing the rate of conversion of methyltetrahydrofolate to tetrahydrofolate, the active form of folate.
Thus vitamin B-12 deficiency effectively induces a functional folate deficiency, with significant “methylfolate trapping
Pernicious anemia also can cause other problems, such as nerve damage, neurological problems (such as memory loss), and digestive tract problems. People who have pernicious anemia also may be at higher risk for weakened bone strength and stomach cancer.
B12-dependent enzymes Methylmalonyl Coenzyme A mutase, and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), also known as methionine synthase; and the buildup of their respective substrates (methylmalonic acid, MMA) and homocysteine.
The Supply of folic acid for the production of thymine due to methyl transferring facilitated by b12
In the form of a series of tetrahydrofolate (THF) compounds, folate derivatives are substrates in a number of single-carbon-transfer reactions, and also are involved in the synthesis of dTMP (2′-deoxythymidine-5′-phosphate) from dUMP (2′-deoxyuridine-5′-phosphate). It is a substrate for an important reaction that involves vitamin B12 and it is necessary for the synthesis of DNA, and so required for all dividing cells.[16]
The pathway leading to the formation of tetrahydrofolate (FH4) begins when folic acid (F) is reduced to dihydrofolate (DHF) (FH2), which is then reduced to THF. Dihydrofolate reductase catalyses the last step.[90] Vitamin B3 in the form of NADPH is a necessary cofactor for both steps of the synthesis. Thus, hydride molecules are transferred from NADPH to the C6 position of the pteridine ring to reduce folic acid to THF.[91]
Methylene-THF (CH2FH4) is formed from THF by the addition of a methylene bridge from one of three carbon donors: formate, serine, or glycine. Methyl tetrahydrofolate (CH3-THF, or methyl-THF) can be made from methylene-THF by reduction of the methylene group with NADPH.
Another form of THF, 10-formyl-THF, results from oxidation of methylene-THF or is formed from formate donating formyl group to THF. Also, histidine can donate a single carbon to THF to form methenyl-THF.
Vitamin B12 is the only acceptor of methyl-THF, and this reaction produces methyl-B12 (methylcobalamin). There is also only one acceptor for methyl-B12, homocysteine, in a reaction catalyzed by homocysteine methyltransferase. These reactions are of importance because a defect in homocysteine methyltransferase or a deficiency of B12 may lead to a so-called "methyl-trap" of THF, in which THF is converted to a reservoir of methyl-THF which thereafter has no way of being metabolized, and serves as a sink of THF that causes a subsequent deficiency in folate.[84] Thus, a deficiency in B12 can generate a large pool of methyl-THF that is unable to undergo reactions and will mimic folate deficiency.
The reactions that lead to the methyl-THF reservoir can be shown in chain form:
folate → dihydrofolate → tetrahydrofolate ↔ methylene-THF → methyl-THF
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0012244
in fact, the most common Alzheimer’s drug works by boosting acetylcholine).
First, the vitamins appeared to halve shrinkage across the whole brain compared with the brains of the people taking the placebo pill. But second, and very significantly, the vitamins only benefited people who had a high homocysteine level — over 13 (a healthy level is said to be between about seven and ten).
FIGURE 23.16 The biosynthesis of cysteine in animals. (A stands for acceptor.)
Methyl transfer from S‐AdoMet is highly favored chemically and metabolically. First, transfer of the methyl group relieves a positive charge on the Sulfur of S‐AdoMet. Secondly, the bond between the Sulfur and the 5′ carbon of the adenosine is rapidly hydrolyzed, leaving homocysteine and free adenosine. This last step is important, because the product remaining when S‐AdoMet gives up its methyl group, S‐adenosyl‐homocysteine, is a potent inhibitor of methyltransferases. Cleavage of this product removes the inhibitor from the reaction.
Homocysteine itself is converted to methionine by the transfer of a methyl group from N5‐methyl‐tetrahydrofolate to homocysteine, regenerating methionine. The methyl group of N5‐methyl‐tetrahydrofolate is derived from serine, originally, so the net effect of this pathway is to move methyl groups from serine to a variety of acceptors, including homocysteine, nucleic acid bases, membrane lipids, and protein side chains. Serine itself is easily made from 3‐phosphoglycerate by an amino transfer reaction, followed by cleavage of the phosphate.
Glutathione id important it acts as a free radical scavengers
Serine (α-amino-β-hydroxypropionic acid) is necessary for the condensation reaction with homocysteine to cystathionine (transsulfuration, cysteine) and also in the folic acid cycle during the reaction of tetrahydrofolate (THF) to 5,10 methylene-THF. Besides, serine is used as a precursor of the biosynthesis of purine bases and of certain phosphoglycerides (components of biological membranes). Therefore, the human body requires large amounts of it. Serine is produced from 3-phosphoglycerate, an intermediate product of glycolysis. Serine-hydroxymethyltransferase (SHMT) [EC 2.1.2.1.] transfers the hydroxymethyl group to THF by producing 5,10-methylen-THF, the original central linkage for the carbon atom transfer for the pyrimidine synthesis and the methylation cycle. Hence, SHMT plays an important role in the carbon metabolism.
Serine and glycine (α-aminoacetic acid) directly depend on one another and can easily be converted into each other as long as there is availability of folate and vitamin-B6. During the glycine synthesis, the β-carbon atom of serine is transferred to THF whilst glycine can be converted from THF to serine by taking on a hydroxyl methyl group: Serine + THF « Glycine + Methylene-THF + H2O. This reaction is catalysed by the (equally vitamin-B6-dependent) enzyme serine-transhydroxymethylase. Glycine also is very significant as the (inhibiting) neurotransmitter in the spinal cord and the brain stem.
http://www.benbest.com/health/Meth.html
The researchers assigned 390 Type 2 diabetes patients at the outpatient clinics of three nonacademic hospitals to take either metformin or a placebo pill three times per day for more than four years. The average study participant had been diagnosed with diabetes 13 years prior and had been undergoing insulin treatment for seven years. Average participant age was 61.Among those taking metformin, vitamin B12 levels began to steadily drop relative to those who were taking a placebo pill. The biggest drop occurred in the first few months, but the decrease continued over the course of the study.After four years, participants in the metformin group had undergone a 19 percent relative reduction in their levels of the nutrient. They were 11.2 percent more likely than placebo participants to suffer from B12 insufficiency and 7.2 percent more likely to suffer from deficiency.
In order to examine the action of vit.B12 on cells of the human immune system, lymphocyte subpopulations and NK cell activity were evaluated in 11 patients with vit.B12 deficiency anemia and in 13 control subjects. Decreases in the number of lymphocytes and CD8+ cells and in the proportion of CD4+ cells, an abnormally high CD4/CD8 ratio, and suppressed NK cell activity were noted in patients compared with control subjects. In all 11 patients and eight control subjects, these immune parameters were evaluated before and after methyl-B12 injection. The lymphocyte counts and number of CD8+ cells increased both in patients and in control subjects. The high CD4/CD8 ratio and suppressed NK cell activity were improved by methyl-B12 treatment. Augmentation of CD3−CD16+ cells occurred in patients after methyl-B12 treatment. In contrast, antibody-dependent cell-mediated cytotoxicity (ADCC) activity, lectin-stimulated lymphocyte blast formation, and serum levels of immunoglobulins were not changed by methyl-B12 treatment. These results indicate that vit.B12 might play an important role in cellular immunity, especially relativing to CD8+ cells and the NK cell system, which suggests effects on cytotoxic cells. We conclude that vit.B12 acts as an immunomodulator for cellular immunity.
In conclusion, we found a significant decrease in the absolute number of CD8+ cells and suppressed NK cell activity in vit.B12-deficient patients. These abnormalities could be at least partly restored by methyl-B12 treatment. Moreover, augmentation of CD8+ cells by methyl-B12 treatment was observed even in control subjects. These observations may contribute to our understanding of the potential anti-tumor effects of vit.B12, and may partly explain the high risk of gastric carcinoma in PA; our data also provide a rationale for considering the use of vit.B12 for treating a variety of other immunological, neurological, and oncological disorders.
Effect of methyl-B12 administration on lymphocyte subsets and NK cell activity in patients and control subjects
leucocyte counts and lymphocyte counts, CD4+, CD8+, CD56+ cell counts and NK cell activity were measured at the end of the 2-week treatment with methyl-B12. Results of statistical analysis of immunological parameters before and after methyl-B12 administration in both patients and control subjects are summarized in this table. The leucocyte counts and lymphocyte counts of patients were increased significantly after methyl-B12 treatment (P < 0.05). After treatment, the lymphocyte counts was still significantly lower in patients than in control subjects (P < 0.05). Interestingly, an increase in the lymphocyte counts was observed even in control subjects (P < 0.05).
The CD8 cell is an immune system T lymphocyte believed to "put the brakes on" the immune system, making the allergy patient less sensitive to allergens such as pollen, cats, and mold. Typically, allergic individuals have numbers of the CD8 suppressor cells that are low relative to CD4 aggressor cells.
http://www.patentstorm.us/patents/6255294/description.html
When Vitamin B12 is delivered parenterally, it passes into the circulation for distribution throughout the body before arriving at the liver. It is during this first pass in its native form that it is believed to exert its therapeutic effect.
Administer hydroxocobalamin (Cyanokit) or the Cyanide Antidote Kit if a diagnosis of cyanide toxicity is strongly suspected, without waiting for laboratory confirmation.
Hydroxocobalamin, routinely used in Europe, has been approved by the US Food and Drug Administration (FDA) for treating known or suspected cyanide poisoning. Hydroxocobalamin combines with cyanide to form cyanocobalamin (vitamin B-12), which is renally cleared.[7, 8]
The Cyanide Antidote Kit contains amyl nitrite pearls, sodium nitrite, and sodium thiosulfate. Amyl and sodium nitrites induce methemoglobin in red blood cells, which combines with cyanide, thus releasing cytochrome oxidase enzyme. Inhaling crushed amyl nitrite pearls is a temporizing measure before IV administration of sodium nitrite.
Sodium thiosulfate enhances the conversion of cyanide to thiocyanate , which is renally excreted. Thiosulfate has a somewhat delayed effect and thus is typically used with sodium nitrite for faster antidote action.
Borron SW, Baud FJ, Mégarbane B, Bismuth C. Hydroxocobalamin for severe acute cyanide poisoning by ingestion or inhalation. Am J Emerg Med. Jun 2007;25(5):551-8. [Medline].
Borron SW, Baud FJ, Barriot P, Imbert M, Bismuth C. Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation. Ann Emerg Med. Jun 2007;49(6):794-801, 801.e1-2. [Medline].
Not only does the cyanide in cyanocobalamin poison you like some crazy rendition of Arsenic and Old Lace, the cyanide actually depletes your body of stored methyl groups. At the same time, these methyls are needed to synthesize cobalamin in your liver.
he discovery of vitamin B(12), the elucidation of its role in metabolism, and the effects and treatment of its deficiency occurred in distinct phases over more than 100 years, and it was the subject of two separate Nobel Prizes. The valuable contribution of clinical reports and studies of patients with pernicious anemia throughout the 19th century resulted in enough clinical definition to allow Minot and Murphy to put together the first hallmark study on treatment of the condition, leading them to a Nobel Prize. These researchers were not the first to suggest that an inadequacy of nutrients was the cause of pernicious anemia, but their particular input was a carefully designed intervention in well-characterized pernicious anemia patients, of a special diet containing large amounts of liver. They found consistent improvement in the clinical and blood status of all subjects, most of whom remained on remission indefinitely. After the successful intervention studies, the next advance was made by Castle who discovered that a gastric component, which he called intrinsic factor, was missing in pernicious anemia. Many years later, intrinsic factor was found to be a glycoprotein that formed a complex with vitamin B(12), promoting its absorption through ileal receptors. The vitamin was isolated by two groups simultaneously and was crystallized and characterized in the laboratory of Dorothy Hodgkin, contributing to her Nobel Prize in 1964. Subsequently, the various biochemical roles of vitamin B(12) were elucidated, including its important interaction with folate and their common link with megaloblastic anemia. Many of the early clinical studies recognized that vitamin B(12) deficiency also caused a severe neuropathy leading to paralysis and death, while post mortem analysis demonstrated spinal cord demyelination. Vitamin B(12) is still the subject of intense research and, in particular, its role in preventing these irreversible neurological lesions remains unclear.