GIT physiology 5 Flashcards
transcriptional regulators
vitamins A and D binds to receptors that form a transcriptional regulatory complex that changes gene expression
- vitamin D receptor is a transcription factor
- Retinoic X receptor is a transcription factor (vit A)
- vit K modifies existing proteins by adding carboxyl groups to increase activity
action of Vit K on transcription
modifies structure of existing proteins to increase their activity via glutamate residue carboxylation
ROS
reactive oxygen species
- proteins and sugars - glycation
- DNA - mutations
- membranes - lipid peroxidation
reactive oxygen species examples
OH, H2O2, O2
effects of ROS
- proteins and sugars - glycation
- DNA - mutations
- membranes - lipid per oxidation
vitamin classification
lipid soluble - A, D, E, K
water soluble - all others
lipid soluble vitamins
hydrophobic, absorbed with lipids using bile
- transported in blood in lipoproteins or attached to specific binding proteins
more likely to accumulate in the body and lead to toxicity hypervitaminosis
water soluble vitamins
8x B vitamins and vit C
- hydrophilic and dissolve in water
- not readily stored, excreted from the body
- does not cross plasma membranes, need carrier proteins
- consistent daily intake is needed and deficiency problems are common
- many types of water soluble vitamins are synthesised by bacteria and fungi, small amounts synthesised in GI tract
vit B1
thiamin
vit B2
riboflavin
vit B3
niacin
vit B4
pantothenic acid
vit B6
pyridoxine and pyridoxamine
vit B 7
biotin
vit B9
folic acid
vit B12
cobalamin
Vit C
ascorbic acid
thiamin
B1 used to form thiamin pyrophosphate coenzyme used in: - CHO and AA metabolism - DNA/RNA/neurotransmitter synthesis - TCA cycle
thiamin deficiency
problems with energy and neurotransmitter production
beriberi
deficiency of thiamin
- CNS problems: memory loss, confusion, ataxia (gait coordination)
- peripheral neuropathy - muscle weakness, muscle wasting
- wernickle-korsakoff syndrome - alcohol induced dementia
deficiency of thiamin is called
beriberi
toxicity symptoms of thiamin
no toxicity symptoms due to water solubility
wernickle-korsakoff syndrome
chronic alcohol use interferes with absorption of Vit B1
alcohol induced dementia
B1 chronic deficiency
riboflavin used to make
forms coenzyme flavin-mononucleotide (FMN) and flavin adenine dunucleotid (FAD)
FMN and FAD
coenzymes formed from riboflavin prosthetic groups for many redox enzymes - coenzymes in proton transformation - TCA cycle - beta oxidation of fatty acids
riboflavin is
B2
riboflavin deficiency occurs in
B2 deficiency is rare
- only occurs with proliferation in high cell turnover tissues
symptoms of riboflavin deficiency
- problems with proliferation in high cell runner tissues
- inflammation in the lining of the mouth and tongue
- dry and scaling skin keratitis, dermatitis and iron deficiency anaemia
riboflavin toxicity
no toxicity
niacin is
B3
niacin comes in
2 forms
- nicoinic acid and nicotinamide
niacin in used to make
NAD and NADP
NAD and NADP are used in
coenzymes in CHP, lipids, AA metabolism (TCA cycle)
biosynthesis of niacin
liver can slowly synthesise niacin from tryptophan (essential AA)
deficiency of niacin
effects tissue with high energy requirements of cellular turnover
- pellagra - a serious deificiency of niacin
- four D’s - diarrhoea, dermatitis, dementia and death
pellagra
serious deficiency of niacin
symptoms of pellagra
four D’s - diarrhoea, dermatitis, dementia, and death
pellagra occurs in
alcoholics, strict vegetarians, those with poor nutrition
- very rare - common in food
toxicity of niacin B3
no toxicity
pantothenic acid is
B5
pantothenic acid forms
acetyl Co-A
acetyl Co-A is made of
pantoic acid and beta-alanine
Co-A is essential for
TCA cycle
metabolism of fatty acids
formation of sterols
- acetylcholine production
deficiency of pantothenic acid
EXTREMELY rare because its is very ubiquitous
- hypothetically it would cause general metabolic deficiencies and neurological problems
toxicity of pantothenic acid
no toxicity
pyrodoxine is
B6
pyridoxine does
group of 3 related compounds
precursor of active coenzyme pyridoxal phosphate - PLP
- coenzyme in amino acid synthesis and gluconeogenesis
PLP is essential for
- RBC metabolic, haemoglobin formation
- neurotransmitter biosynthesis
deficiency is pyridoxine
anaemia
neurological problems
inflammation of the GI tract - stomatitis, glossitis and dermatitis
B6 toxicity
toxicity above 200mg/day
biotin is
B7
biotin is used for
prothetic group of several ATP-dependant carboxylase enzymes
coenzyme for FA synthesis, gluconeogenesis, CHO, fat and protein metabolism
defificency of biotin
very rare
inflammation of the GI tract and skin
consumption of raw eggs
produced by gut bacteria
toxicity of biotin
no toxicity
folic acid is
B9
folate
pteroglutamic acid
once de-glutamated to be folic acid, then hydrated is becomes tetrathydrofolate
tetrahydrofolate
coenzyme of many tranferases
- essential in purine and pyrimidine synthesis
deficiency of folic acid
very rare
- effects high turnover/RNA synthesis)
- suppression of nervous system
folic acid deficiency in pregnant women
leads to major birth defects
neural tube defects - span bifida
cobalamin
vitamin B12
cobalamin catalyses which reactions
catalyses reactions of two enzymes
- methionine synthase - DNA synthesis
- methylmalonyl-CoA mutase - energy metabolism
cobalamin is essential for
energy metabolism ‘
purine and pyrimidine synthesis
RBC maturation, cell growth, nervous system maturation
deficiency of B12 is common in
vegetarians and vegans
deficiency of B12 causes
effects high turnover/RNA synthesis
- microcytic anaemia and nervous system problems
2 antioxidant vitamins
E - lipid soluble
C - water soluble
lipid soluble antioxidant
E
water soluble anti oxidant
C
vit E protects from
lipid peroxidation, membranes, membrane bound proteins
vit E protects from
free radicals in solution (DNA< non-membrane bound proteins
what do vit E and C do
get rid of free radicals
ascorbic acid is
vit C
the principle water soluble antioxidant and free radical scavenger
ascorbic acid is involved in
- cofactor in the synthesis of noradrenaline
- leukocyte motility
- synthesis of collagen
deficiency of vit C is called
scurvy
scurvy
occurs over 3-5 months
neuronal problems - fatigue, decline in psychomotor performance and motivation, dyspnoea
- collagen problems - spongy gums, and bleeding from all mucus membranes and loss of teeth
tocopherol is
vit E
a family of 4 tocopherols
most common is a-tocopherol
tocopherol does
antioxidant
- prevents lipid peroxidation
- stops free radical reactions
deficiency of tocopherol
impairment in fertility in men
peripheral neuropathy
- anaemia, diminished RBC lifespan
- virtually never occurs
toxicity of tocopherol
rare, increased bleeding
retiniocs acid is
vit A
precursors of vit A
carotenoids (plants) and retinol esters (animal)
functions of retinoic acid
transcriptional regulation - retinioc X receptor is a TF
visual pigment - forms rhodopsin in retinal photoreceptors
toxicity of retinoic acid
acute - headache, vimiting, impaired consciousness
chronic - weight loss, vomiting, joint pain, blurred vision, hair loss, excessive bone growth
retiniocs acid in pregnancy
both excess and deficiency are teratogenic
retiniocs acid in chemotherapy
is chemotherapeutic
used to kill rapidly proliferating cells
vit D
not a vitamin
synthesised in the skin
vit D3 made from
7-dehydrocholesterol + UVB
vit D2 from
vitamin supplements
transformations of D3
cholecalciferol
calcidiol
calcitriol
calcitriol
transported in the blood on a carrier - VDBP - vitamin D binding protein
binds vitamin D receptor - transcription receptor
regulates Ca2+ levels
- increase Ca2+ absorption
- switches on genes of Ca2+ transporters and Ca2+ binding proteins
deficiency of calcitriol
causes Ca2+ deficiency
deficiency of calcitriol happens due to
malabsorption or lack of UVB
calcitriol is
vit D
Ca2+ deficiency in developing child is called
rickets
symptoms of Ca2+ deficiency
soft and pliable bones = impaired ossification
osteomalacia in adults - after closure of epiphyseal plates
vitamin DD is used to make
TRPV6 - calcium transporter
and calbindin which binds free calcium inside cell to lower concentration of free calcium allowing calcium to flow into the cell along its concentration gradient
koagulationsvitamin is
vit K
2 forms of koagulationsvitamin
K1 - phylloquinon - plants
K2 - menaquinon -animals/bacteria
koagulationsvitmain does
coenzyme for y-glutamyl carboxylase
y-glutamyl carboxylase
carboxylates glutamate residues in specific proteins to activate function
vit K dependant proteins
blood coagulation - prothrombin (Factor 2), factors 7, 9, 10, and proteins C, S, Z
bone metabolism - osteocalcin, matriculates Gla protein (MGP), periostatin
deficiency of vit K
rare because vit K is abundant in the diet
causes fat malabsorption and liver failure
blood clotting disorders - may be dangerous in newborns
osteoporosis due to decreased activity of osteoblasts
toxicity of vit K
no toxicity
absorption of lipophilic vitamins
co-absorption with digested fat in bile salt micelles
absorption of water soluble micelles
specific transporters
except B12
how does B9 get into the cell
B9 has lots of glutamate residues
all except 1 glutamate must be removed
folate conjugase removes glutamate residues
enters through folate transporter
dihydrofolate reductase sticks on a methyl group and 4 hydroxyl groups
transported into plasma
carried around as methyl tetrahydrofolate
how does vit B12 enter the cell
via receptor mediated endocytosis
receptor binds to intrinsic factor and intrinsic factor binds to B12 - receptor cannot bind directly to B12
intrinsic factor secreted in the stomach but the pH is too low to bind intrinsic factor to vit B12 in the stomach
haptocorrin binds B12 in the stomach
proteases digest haptocorrin in the duodenum but do not ingest intrinsic factor because it is covered in sugars
intrinsic factor binds B12 and there is receptors for intrinsic factor in the ileum
endoscope forms and enzymes liberate intrinsic factor
Vit B12 binds transcobalamin 2 and enters plasma
cells have a receptor for transcobalamin 2
what liberates Vit B12 from food
pepsin liberates Vit B 12
haptocorrin
binds vit B 12 in he acidic stomach
why can’t intrinsic factor binds vit B12 in the stomach
too acidic
where is cobalamin taken up
in the ileum binded to intrinsic factor
what happens to haptocorrin in the duodenum
proteases digest haptocorrin to liberate the cobalamin and the cobalamin binds the intrinsic factor
why isn’t intrinsic factor digested in the duodenum
covered in sugars so the proteases can’t reach it
how it cobalamin transported through plasma
bound to transcobalamin 2
how is cobalamin taken up into cells from plasma
receptor mediated endocytosis by binding transcobalamin 2
having toxic effects due to too much of a vitamin is called
hypervitaminosis
