Download Vitamins Clinical relevance: homocystinuria: B6 and/or B12 and/or

Vitamins
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Clinical relevance:
o homocystinuria: B6 and/or B12 and/or folate
Cofactors
o organic/metal ions that work with enz
o provide special chemical reactivity/structural properties to drive rxns
classification:
Loosely bound: bind, carry rxn, dissociate (ATP, Mg++)
tightly bound: covalent attachment or strong non-covalent interactions
o heme: biotin and lipoic acid (covalent)
o flavins: Zn++ via (non-covalent, electrostatic)
Metabolite Cofactors
o produced by metabolic pathways and used by other enzymes to carry out key
rxns:
 ATP
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S-Adenosylmethonine: donates methyl to nearly all biochemical rxns
requiring it
UDP-glucose: glycogen synthesis
GTP, UTP, CTP, ATP: DNA synthesis
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 each on some level involved on metabolic process METABOLite
Vitamin-derived Coenzymes
o Vitamin C: consume in diet; used as-is
 donates electrons to reduce targets
 ascorbic acid
o
o
Most vitamins transformed before can be used (panthothenic acid CoA)
rxn occurring between dbl bond b/n 2 carbons with the OH group
CoA: carries acyl groups in metabolism; made from B5 and ADP cofactor (so is
B5 panthothenic acid?)
Nicotinamide Coenzymes
o rxns involving Hydride (H-) ion (proton and 2 electrons) H… reducing
equivalents
o NADP+/NADPH same, but has phosphate group attached to C2 of ribose
o
NAD+/NADH
o donates/accepts 1 proton and 2 electrons as a hydride ion (H:-)
o dehydrogenases
o true cosubstrate: binds like substrate, exits like product
o NADH—carry electrons to mitochondria to drive ATP production
o
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o
o
Flavins
o
o
o
o
o
o
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NADPH used in FA and cholesterol synthesis
NADH oxidized  NAD+ as pyruvate is reduced  lactate
NADH= reducing agent
FMN= flavin mononucleotide
FAD= flavin adenine dinucleotide
roles of Flavins and NAD+/NADH are similar
carries electrons reducing equivalents
2 electrons and 2 protons transferred as one electron and one proton
simultaneously (2 electrons and 1 proton in case of NAD/NADH)
FMN
o
FAD
FMN/FAD
o both forms have same fxnl end: 2 N atoms in ring
o redox rxns occurring in 2 steps
o Electron transport in mitochondria to drive ATP production
o xenobiotic drug metabolism via cytochrom P450, lipid metabolism, antioxidant
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CoA
o
o
one of most common in metabolic pathways
acyl group carrier- Acetate most common; FA or ketone can be transferred as
well
o
o
o
o
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S atom with carbonyl activates for reactivity
thio-ester bond
–SH part of CoA is nucleophilic and attacks the C=O; releases water and forms
new bond between S-C=O
Thiamine Pyrophosphate
o decarboxylation and transketalation: transfer of aldehyde group
o neuronal and neurogocnitive function (synthesis of ACh, nucleic acids, and
NADPH)
o carbon in ring= strong nucleophile
Pyridoxyl Phosphate
o
o
o
o
o
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B6 derivative
aldehyde group- fxnl center
covalently attached to host enzyme
interacts with amino acids: isomerizations, decarboxylation, side chain removal
can depend on NADH, folic acid
Biotin
o used as-is (like vitamin C)
o covalently attached to Lys
o carboyl transfer rxns and ATP-dependent carboxylations (opp of Thiamine which
decarboxylates)
o metabolism (PEP oxaloacetate, fatty acid synthesis)
o raw eggs- bind all biotine; ppl who eat a lot have thin hair and scaly skin
Tetrahydrofolate
o transfer of one-carbon units in form of methyl, methylene, and methenyl
o 2 N= fxnl center
o critical for neurological fxn and development
o THF and single carbon transfer
Lipoamide
o formed from lipoic acid
o becomes lipoamide when covalently attached to protein Lys side chain (Biotin
also binds Lys side chain)
o Acyl group carrier
o “swings” from one active site to another
o redox properties too
 SS= oxidized
 SH= reduced
 NADH reduced from NAD+ when lipoamide oxidized
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Cobalamin
o B12
o Adenosylcobalamin: catalyzes exchange reactions: isomerizations
o methylcobalamin: transfers methyl groups
o methylcobalamin and methionine
 homocysteine is intermediate in synthesis of Met
 THF- donates methyl
 methylcobalamin drives transfer reacion
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Lipid-soluble vitamins
o A- vision
o K- blood clotting
o E- antioxidant properties
o D- Ca2+ uptake
Heme
o prosthetic group
o tightly/covalently bound to host protein
Tightly-bound metals
o iron-sulfur clusters: electron transfer reactions, esp in TCA cycle
o Zn++: electrostatic interactions w/substrates to control position of substrate or to
activate a bond or reactive group
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