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Transcript
Enzymes and their Cofactors
Source:
Biochemistry: An Illustrated Review
Table 1.4 Water-soluble Vitamins: Sources and Functional Forms
Vitamin
Source
Functional Form
B2 (riboflavin)
Milk, eggs
Flavin mononucleotide and
flavin adenine dinucleotide
(FMN, FAD)
B3 (niacin)
Meat, yeast products, fruits,
vegetables, synthesized from
tryptophan
Nicotinamide adenine
dinucleotide and nicotinamide
adenine dinucleotide phosphate
(NAD+ and NADP+)
C (ascorbic acid)
Fruits, vegetables
Ascorbate
B1 (thiamine)
Grain, yeast products, pork
Thyamine pyrophosphate (TPP)
B5 (pantothenic acid)
Widely distributed
Coenzyme A
B6 (pyridoxine)
Meat, vegetables, grains
Pyridoxal phosphate
B12 (cobalamin)
Meat, liver, milk, eggs
Adenosylcobalamin
methylcobalamin
Biotin
Yeast products, legumes, nuts
Biotin
Folate
Fresh green vegetables, liver
Tetrahydrofolate (THF)
Involved in redox reactions
Involved in nonredox reactions
Table 1.6 Vitamins Involved in Nonredox Reactions, Their Associated Enzymes and Functions
Vitamin
Cofactor and Its Associated Enzyme and
Function
B1 (thiamine)
Thyamine pyrophosphate (TPP) is a cofactor for:
-- Pyruvate dehydrogenase complex: This enzyme
decarboxylates pyruvate to generate acetyl
coenzyme A (CoA)
-- a-ketoglutarate dehydrogenase complex: This
tricarboxylic acid (TCA) cycle enzyme
decarboxylates a-ketoglutarate to generate
succinyl CoA
1
-- Branched chain a-keto acid dehydrogenase:
This enzyme plays a role in the degradation of
branched chain amino acids isoleucine, leucine
and valine
-- Transketolase: This enzyme transfers twocarbon fragments between molecules in the
pentose phosphate pathway
B5 (pantothenic acid)
Pantothenic acid is a component of:
-- Coenzyme A: This molecule forms high-energy
thioester bonds with other molecules to "activate"
them and is involved in reactions that transfer
fatty acyl groups between molecules
-- Fatty acid synthase (FAS) complex: This
enzyme catalyzes the synthesis of fatty acids
B6 (pyridoxine)
Pyridoxal phosphate is a cofactor for:
-- Transaminases: These enzymes transfer amino
groups between molecules to interconvert amino
acids and alfa-keto acids
-- Decarboxylases: These enzymes catalyze the
removal of carboxyl groups. Specific
decarboxylases play a critical role in the synthesis
of neurotransmitters (e.g., dopamine)
-- Glycogen phosphorylase: This enzyme is
involved in the breakdown of glycogen
(glycogenolysis)
-- Aminolevulinic acid (ALA) synthase: The ratelimiting step in heme and porphyrin synthesis is
catalyzed by this enzyme
B12 (cobalamin)
Adenosylcobalamin and methylcobalamin are
cofactors for:
-- Methylmalonyl CoA mutase: This enzyme
isomerizes methylmalonyl CoA into succinyl CoA
in a reaction that is part of the pathway that
degrades odd-numbered fatty acids
-- Methionine synthase/homocysteine
methyltransferase: This enzyme transfers a methyl
group from 5-methyltetrahydrofolate (N5-methylTHF) onto homocysteine to form methionine.
Methionine reacts with adenosine triphosphate
(ATP) to generate S-adenosyl methionine (SAM),
the latter of which regenerates homocysteine
when SAM donates a methyl group to target
molecules.
Biotin
Biotin serves as a cofactor for:
2
-- Pyruvate carboxylase: This enzyme irreversibly
carboxylates pyruvate to produce oxaloacetate
-- Acetyl CoA carboxylase: This enzyme
irreversibly carboxylates acetyl CoA to form
malonyl CoA
Folate
Methyltetrahydrofolate (methyl-THF) is used as a
source of methyl groups, which are transferred to
various molecules. Methyl-THF is used in the
biosynthesis of the purine nucleotides and
thymidylate.
Table 1.14 Enzymes that Utilize Zn as a Cofactor
Enzyme
Action
Superoxide dismutase
This antioxidant enzyme binds the free radical of
molecular oxygen
Collagenases
Belongs to the family of matrix
metalloproteinases. They are the only enzymes
capable of degrading triple helical collagen. They
play a major role in tissue repair and remodeling.
Alcohol dehydrogenase
Converts alcohol to acetaldehyde
Alkaline phosphatase
Mineralizes bone salts
Transcription factors
Several proteins that contain Zn-finger domains
bind to specific sequences on DNA and regulate
transcription
Carbonic anhydrase
Interconverts CO2 and bicarbonate to balance pH
Table 1.15 Enzymes that Utilize Cu as a Cofactor
Enzyme
Action
Cytochrome-c oxidase
Accepts electrons from cytochrome-c in the
electron transport chain
Ferroxidase (ceruloplasmin)
Oxidizes ferrous iron (Fe2+ ) into ferric iron (Fe3+)
Superoxide dismutase
This antioxidant enzyme binds the free radical of
molecular oxygen
Lysyl oxidase
Cross-links collagen and elastic tissue during
wound healing
Tyrosinase
Synthesizes melanin
3
Table 1.18 Trace Elements and Their Uses
Microelements
Use
Mo
A cofactor for oxidases (xanthine oxidase,
aldehyde oxidase, and sulfite oxidase);
antagonistic to Cu2+
Mn
A cofactor for pyruvate carboxylase, which
converts pyruvate to oxaloacetate
A cofactor for superoxide dismutase, which binds
the free radical of molecules oxygen
A cofactor for arginase, which catalyzes the
formation of urea from arginine
A cofactor for malic enzyme, which catalyzes the
oxidative decarboxylation of malate to pyruvate
and CO2
Co
Found in cobalamin (vitamin B12)
Cr
Involved in the activity of insulin to reduce blood
glucose levels
S
Found in coenzyme A, glutathione and Sadenosylmethionine
I
Required for the synthesis of thyroid hormones
such as circulating thyroxine (T4) and the
intracellular active hormone triiodothyronine (T3).
They play an important role in growth,
development, and metabolic processes.
Insufficient dietary intake of iodine leads to
endemic goiter.
Se
A cofactor of glutathione peroxidase, an important
antioxidant enzyme that detoxifies hydrogen
peroxide; required for the conversion of the
thyroid hormone T4 to T3
F
Fluorine is not a proper bone salt, but it prevents
demineralization of teeth (dental caries)
4