Midterm 1 (Lecture 4) Flashcards
Vitamin B6
Six related compounds:
-Pyridoxal, pyridoxine, pyridoxamine and their phosphates
- phosphorylated in foods
- phosphate removed by intestinal enzymes before absorption
- taken up by tissues and re phosphorylated
Coenzyme form: pyridoxal phosphate (plp)
Riboflavin is needed to convert vitamin six to its coenzyme form PLP
Vitamin b six metabolic role
Amino acid metabolism: - transamination, de carboxylation, r group interconversion
Aa metabolism involved in many aspects of intermediary metabolism
4 examples to study
Vitamin B six metabolic role example one
Nervous System
- synthesis of neurotransmitters involve PLP dependent enzymes
Example: serotonin, dopamine
Serotonin synthesized from tryptophan
-Vit B six deficiency = neurological problems
Vitamin B six metabolic role example two
Glycogen breakdown
Hormone function
- PLP can bind to steroid hormone receptors- in nucleus
- inhibits binding of hormone - decreases effects
- steroid responsiveness lower in vitamin B six sufficient vs deficient animals
- implications for steroid dependent diseases (could B six supplements help decrease estrogen levels ex - breast cancer)
Vitamin B six metabolic role example three
Glycogen breakdown
- PLP involved in glycogenolysis
- coenzyme for glycogen phosphorylase
- key enzyme in conversion of glycogen to glucose ( could B six improve glycogen conversion and improving human performance)
Vitamin b6 metabolic role example four
Red blood cell formation and function
PLP involved in synthesis of heme protein
- acts as a coenzyme in heme synthesis
- heme is a component of hemoglobin
- it allows RBC to transport oxygen throughout body
IMINE group
PLP binds to the enzyme (physical interaction) as a coenzyme
The link formed between PLP and the enzyme is called an IMINE group
Assessing vitamin b6 status
assessing based off fact that build up of a substrate/metabolite means deficiency of enzyme
TRYPTOPHAN LOAD TEST
- impaired conversion to niacin
- build up of urinary kynurenic acid (derived from Kynureine pathway
- we know Kynureine needs b6 therefore build of this acid means B6 deficiency
METHIONINE LOAD TEST
- PLP dependent step in methionine metabolism
- methionine is converted to homocysteine which then builds up since PLP is needed to convert homocysteine to cysteine
- increased homocysteine
4-PYRIDOXIC ACID
- major urinary metabolism that is ABSENT with vitamin b6 deficiency
Vitamin B6 deficiency
Nervous system symptoms
- irritability, depression, confusion, sleepiness
- 1950,s formula incident ; seizures observed in infants due to manufacturing error of formula destroying B6
- dermatitis
- cheilosis (lip lesions)
- stomatitis ( inflammation of mouth and lips)
SIMILAR TO B2 deficiency BECAUSE We need B2 to make B6
Vitamin B6 requirement
Affected by
- protein intake (more Amino acids eaten means more B6 produced)
- alcoholism
- pregnancy lactation
Vitamin B6 Drug Interactions
- Anti tuberculosis medications
- anti convulsant medications
High doses of vitamin B6 can decrease efficacy of these drugs by forming complexes with them which:
- decreas3s efficacy of the drug
- decreases vitamin B6 status
Vitamin B6 Health and disease
Cardiovascular disease
- relation to homocysteine
- PLP needed for one Hcy pathway
- PLP shuttles Hcy to cysteine
Depression
- PLP dependent neurotransmitter synthesis serotonin
Premenstrual syndrome (PMS)
- vitamin B6 relieves pms (decreases hormone effects)
Vitamin B12
Largest and most complex structure of B vitamins
Cobalt central part of structure (look for Co in centre of structure)
Also called cobalamin
R group
- R = methyl
- R = adensoyl
- R = CN (supplement form)
Vitamin B12 - Absorption
Complicated process
Three phases involved in its absorption dependent on pH :
- gastric phase
- luminal phase
- mucosal phase
Intrinsic Factor
Key to vitamin B12 absorption
Glycoprotein released into stomach by parietal cells (decrease with age)
Binds vitamin B12
Allows passage into the ileum - ileum has receptor for IF vitamin B12 complex (in final phase)
Absorption than occurs in the ileum
Vitamin B12 Absorption gastric phase
Digestion of protein bound vitamin B12
Free vitamin b12 now binds with R proteins
Vitamin B12 has a higher affinity for the R proteins than the IF at this point - likely related to low PH
IF is synthesized and released by parietal cells but does not bind vitamin B12 in the stomach
Vitamin B12 absorption Luminal and Mucosal Phase
Luminal Phase
- R proteins are digested
- Vitamin B12 is free
- now vitamin B12 can bind with IF
Mucosal Phase
- receptors for vitamin B12 - IF complex in ileum
- absorption occurs!
Vitamin B12 Metabolic Role
Coenzyme form: methyl cobalamin
- methionine synthetase
- methionine synthesis
- Hcy to methionine
- also needs folate
Coenzyme form: adenosyl cobalamin
- methylmalonyl CoA mutate
- proprionate catabolism
- proprionate to methylmalonyl CoA to succinyl CoA- entry to TCA cycle
Vitamin B12 Malabsoprtion
Atrophic gastritis
- decreased gastric acid
- age related decrease in parietal cells
Decreased intrinsic factor
- age related decrease in parietal cells
Pancreatic insufficiency
- decreased protein digestion
Vitamin B12 deficiency
Elevated urinary concentrations of:
-Homocysteine (less specific)
-Methylmalonic acid
Pernicious anemia
- lack of IF; lack of absorption
- treated by bypassing GIT (IV)
- diagnosed with schilling test (cobalt is labeled)
- neurological symptoms as a result of peripheral neuropathy (memory loss, dementia, tiredness), takes time to develop, confused with “getting old”
Vitamin B12 deficiency - relation to folate
Common megaloblastic anemia
Red blood cells do not develop properly
Folate can mask a vitamin b12 deficiency
Folate can rectify the anemia of a vitamin b12 deficiency but not the neurological symptoms
Can become irreversible
Breath test specifically measures b12 deficiency
Vitamin b12 and older adults
Deficiency increased in elderly
Age related decrease in parietal cells
- atrophic gastritis
- reduced IF
Interactions with medications
Eating less animal product (vitamin b12 in animals only) vegans watch out
Can be masked by folate supplements
Confused with getting old
age is the most major risk factor for vitamin b12 deficiency
