Download Micronutrient Cofactors

Vitamin
A
D
B1
Water
Soluble
(polar) W/
Fat soluble
(isoprene) F
F
F
W
Function
Organic Group
Action
Deficiency/Excess
1) signal
transduction
2) Hormone
1) retinal (aldehyde)
2) retinoic acid
1) part of rhodopsin (opsin + retinal)
11 cis retinal  all trans when
activated by light which activates the
opsin part which stimulates a g protein
that eventually leads to a nerve
response
2) ligands for nuclear hormone
receptor which are transcription
factors that reg. growth, diff,
metabolism, reproduction, and
morphogenesis
once ligand binds complex forms a
dimmer and bind to an upstream
element and facilitate transcription of a
gene downstream. Skin and bone
metabolism gene pathways
ligands for nuclear hormone receptor
which are transcription factors that
reg. growth, diff, metabolism,
reproduction, and morphogenesis
once ligand binds complex forms a
dimmer and bind to an upstream
element and facilitates transcription of
a gene downstream. Skin and bone
metabolism gene pathways
(can form homodimer or heterodimer
with retinoic acid receptor (RAR and
VDR)
genes involved in calcium
homeostasis
Form a transient covalent bond with a
substrate to stabilize charges that are
associated with the transition state.
decarboxylation alpha keto acids/
1) deficiency in retinal leads to
night blindness
2) hormone action deficiency
includes defective
epithelialization and
keratomalacia
(corneal softening permanent
blindness)
Hormone
Electron Sink
(B-carotene is pro vitamin A
cleavage yields 2 retinoids)
7-dehydrocholesterol
activated by sunlight to form
cholecalciferol which is
hydroxylated in the liver (C25) and the kidney (C-1) to
form active 1,25dihydroxycholecalciferol
“Calcitriol and vit D3
Thiamine (provitamin)
TPP
excess: GI discomfort to severe
liver damage/death
Hypocalcemia leads to defects
in bone associated w/ rickets in
kids or
osteomalacia/osteoporosis in
adults
Hypercalcemia leads to renal
failure
Beri Beri family neuron/
cardiomyopathies
Dry: peripheral
neuropathy, sensory/
sugars
B6
W
Electron Sink
Pyridoxine PLP / P5P
Vitamin
B2
W
Redox
Riboflavin
FMN and FAD (flavin
mononucleotide and flavin
adenine nucleotide)
Vitamin
W
Redox
Niacin
Form a transient covalent bond with a
substrate to stabilize charges that are
associated with the transition state
Amino acid metabolism,
decarboxylation, transamination,
deamination
SCHIFF BASE
(also glycogen phosphorylase uses PLP
is which the phosphate is reactive
center instead of aldehyde group)
Flavin ring can accept 2H+ and 2e(reduced to FADH2 or FMNH2) can
accept complete hydrogen molecule
Niacin can only accept hydride ion (2e-
motor weakness
Wet: added edema and
cardiac failure
Cerebral/ WernickeKorsakoff: permanent
brain damage and
chronic confusion/
delirium, impaired
vision and eye
movement and lack of
muscle coordination
(chronic alcohol makes
it worse)
Excess PLP temporary
deadening of proprioceptory
nerves: loss of proprioception
causes unconscious perception
of movement and spatial
orientation arising from stimuli
within the body
Riboflavin similar to bilirubin so
newborns under blue light
control for bilirubin must also
get vitamin B12 supplements so
it is not depleted by the blue
light
Vitamin B2 deficiency causes
irritation to the skin and eyes,
cracked red lips, inflamed
mouth and tongue, mouth
ulcers
Eyes can also be bloodshot,
itchy, watery and sensitive to
bright light
Some bacterial toxins are ADP
B3
NAD+ (nicotinamide adenine
dinucleotide) also NADP +
(one of the hydroxyl groups
on ribose of adenine is
esterified with phosphate)
(niacin+ribose +phosphate
+phosphate +ribose+
adenine)
and 1 H+) NADH
NAD is also the substrate for ADP
ribosylates that attach ADP ribose to a
protein in posttranslational
modification reaction (split NAD into
ADP ribose and nicotinamide and
transfer the ADP ribose to an acceptor
like a protein)
ribosylating enzymes like
diphtheria and pseudomonas
which DP ribosylation of EF-2
which blocks protein synthesis
in host cell
Cholera toxin and Pertussis
toxin modify a specific Gprotein with ADP ribose which
leads to deregulated protein
kinase A
Vitamin B3 deficiency causes
pellagra
4 Ds: diarrhea, dermatitis,
dementia, and death
relationship between B3 and
B6: PLP is a cofactor in the
rxn where niacin is made
from tryptophan (adequate
B6 means you need less B3 in
diet)
K
F
Redox
Redox centers: oxygen’s on
napthoquinone ring
C
W
Redox
Ascorbic acid
Redox cofactor for gamma glutamyl
carboxylase (gla proteins which are
involved in clotting, bone/extracellular
matrix homeostasis and regulation of
growth hormone)
Vitamin K is regenerated by vit K
epoxide reductase (this is where
Coumadin and warfarin act)
Versatile because many redox states
Redox cofactor for enzymatic and non
enzymatic steps
Prolyl and lysyl hydroxylases of the
excessive vit B3 leads to niacin
maculopathy where the macula
and retina thicken which leads
to blurred vision and blindness
Vita K deficiency results in
uncontrolled bleeding
Cartilage calcification and
severe malformation of dev
bone
Deposition of insoluble calcium
salts in the arterial vessel walls
Vit C deficiency only in some
species who can’t make own vit
C
Scurvy= defective collagen
E
F
Redox
Tocopherol ring
collagen synthesis pathway
Functions as antioxidant because it is
stable as a radical form inactivate
free radical species
Antioxidant in soluble cell portions like
cytosol and intraorganelle comp
Antioxidant able to neutralize free
radicals
Activity in membrane compartments
(non polar)
synthesis
Weakens collagen fibrils
Abundant in vegetable oil and
seeds/nuts
Dietary limitations/ fat
absorption problems can cause
vit E deficiency
-impaired balance and
coordination
-injury to sensory nerves
(peripheral neuropathy)
-muscle weakness (myopathy)
damage to retina of the eye
(pigmented retinopathy)
B5
W
Functional
group carrier
Pantothenate, pantothenic
acid combined with
cysteine and phosphate to
make phosphopantothenic
Acyl groups in thioester linkage (has
high delta G hydrolysis)
Makes up coenzyme A
Part of fatty acid synthase
B7
W
Functional
group carrier
Biotin
CO2
Peptide linkage to the host enzyme
ATP hydrolysis is required for CO2
attachment to biotin
The energy associated with the
cofactor condensation reaction drives
the Co2 condensation with the
substrate (acetyl coA is an example)
Pyruvate oxaloacetate
B9
W
Functional
group carrier
Folate, folic acid THF , N5
methyl THF
N5N10 methylene THF
Single carbon units
Folate is unreactive in oxidized form
Must be fully reduced to THF to react
and form covalent linkage to a c1 group
Human diet rich in vitamin B7
and vitamin B5
Too much raw egg can cause
vitamin B7 deficiency
Avidin produced in egg whites
binds with biotin with affinity
approaching covalent linkage
(very small Kd!)
Skin disorders
Hair loss
neuropathy
Homocysteinemia
Megaloblastic anemias
Homocysteine is a dangerous
B12
W
Functional
group carrier
Cobalamin
Folate and dihydrofolate are reduced in
a rxn catalyzed by a reductase enzyme
that uses NADPH as the redox donor
2 linked NADPH reductase enzymes
are required to completely reduce
folate to THF ho
converts homocysteine to methionine
converts serine to glycine
makes thymidylic acid for DNA rep
de novo purines
histidine metabolism
Methyl, adenosyl groups
MeB12
AdoB13
Corrin ring which central metal ion is
cobalt (resembles heme)
4/6 metal coordination sites are
provided by corrin ring nitrogen’s
5th coordination size is with
dimethylbenzimidazole group
6th site is R functional group Me or Ado
succinyl coA (ado)
homocysteine to methionine (me)
metabolite that has to be
regulated (heart pathologies)
B9 and B12 cause dTMP
deficiency and reduces DNA
synthesis thus DNA synth lags
behind cell growth it can cause
premature RBCs to overgrow
Hypersegmented neutrophils in
peripheral blood more than 5
lobes
Homocysteinemia
Megaloblastic anemia’s