Principles of BIOCHEMISTRY

Report
Chapter 7 - Coenzymes and Vitamins
• Some enzymes require cofactors for activity
(1) Essential ions (mostly metal ions)
(2) Coenzymes (organic compounds)
Apoenzyme + Cofactor
(protein only)
Holoenzyme
(active)
(inactive)
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Fig 7.1 Types of cofactors
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Many Enzymes Require Coenzymes
• Coenzymes act as group-transfer reagents
• Hydrogen, electrons, or other groups can be transferred
• Larger mobile metabolic groups can be attached at the reactive
center of the coenzyme
• Coenzyme reactions can be organized by their types of
substrates and mechanisms
Many Enzymes Require Inorganic Cations
• Enzymes requiring metal ions for full activity:
(1) Metal-activated enzymes have an absolute requirement or
are stimulated by metal ions (examples: K+, Ca2+, Mg2+)
(2) Prentice
Metalloenzymes
contain Chapter
firmly
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7 bound metal ions 3at the
enzyme active sites (examples: iron, zinc, copper, cobalt )
Fig 7.2 Mechanism of carbonic anhydrase
• Action of carbonic
anhydrase, a
metalloenzyme
• Zinc ion promotes the
ionization of bound
H2O. Resulting
nucleophilic OHattacks carbon of CO2
(continued next slide)
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Fig. 7.2 (continued)
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Iron in metalloenzymes
• Iron undergoes reversible oxidation and reduction:
Fe3+ + e- (reduced substrate)
Fe2+ + (oxidized substrate)
• Enzyme heme groups and cytochromes contain iron
• Nonheme iron exists in iron-sulfur clusters (iron is
bound by sulfide ions and S- groups from cysteines)
• Iron-sulfur clusters can accept only one e- in a reaction
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Fig 7.3 Iron-sulfur
clusters
• Iron atoms are complexed
with an equal number of
sulfide ions (S2-) and with
thiolate groups of Cys side
chains
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Reactions of ATP, a metabolite coenzyme
• ATP is a versatile reactant that can donate its:
(1) Phosphoryl group (g-phosphate)
(2) Pyrophosphoryl group (g,b phosphates)
(3) Adenylyl group (AMP)
(4) Adenosyl group
Fig 7.4
SAM synthesis
• ATP is also a source of other metabolite coenzymes such as Sadenosylmethionine (SAM)
• SAM donates methyl groups in many biosynthesis reactions
Fig 7.5 S-Adenosylmethionine
• Activated methyl group in red
S-Adenosylmethionine (SAM) is a methyl
donor in many biosynthetic reactions
• SAM donates the methyl group for the
synthesis of the hormone epinephrine from
norepinephrine
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Vitamin-Derived Coenzymes and Nutrition
• Vitamins are required for coenzyme synthesis. Animals must
obtain vitamins from diet. (Plants, microorganisms, meat)
• Most vitamins are enzymatically transformed to the coenzyme
Table 7.1 Vitamins and
nutritional deficiency
diseases
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Vitamin C: a vitamin
but not a coenzyme
• A reducing reagent for hydroxylation of collagen
• Deficiency leads to the disease scurvy
• Most animals (not primates) can synthesize Vit C
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NAD+ and NADP+
• Nicotinic acid (niacin) is precursor of NAD+ and NADP+
• Lack of niacin causes the disease pellagra
• Humans obtain niacin from cereals, meat, legumes
Fig 7.8 Oxidized, reduced forms of NAD+ (NADP+)
NAD+ and NADP+ are cosubstrates
for dehydrogenases
• Oxidation by NAD+ and NADP+ occurs two electrons at a time
• Dehydrogenases transfer a hydride ion (H:-) from a substrate to
pyridine ring C-4 of NAD+ or NADP+
• The net reaction is: NAD(P)+ + 2e- + 2H+
NAD(P)H + H+
Catalysis by lactate dehydrogenase
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FAD and FMN
• Flavin adenine dinucleotide (FAD) and Flavin
mono-nucleotide (FMN) are derived from
riboflavin (Vitamin B2)
• Flavin coenzymes are involved in oxidationreduction reactions for many enzymes
(flavoenzymes or flavoproteins)
• FAD and FMN catalyze one or two electron
transfers
Fig 7.10 Riboflavin and its coenzymes
(a) Riboflavin, (b) FMN (black), FAD (black/blue)
Fig 7.11 Reduction, reoxidation of FMN or FAD
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Coenzyme A (CoA or HS-CoA)
• Derived from the vitamin pantothenate
• Participates in acyl-group transfer reactions with
carboxylic acids and fatty acids
• CoA-dependent reactions include
oxidation of fuel molecules and
biosynthesis of carboxylic acids
and fatty acids
• Acyl groups are covalently
attached to the -SH of CoA
to form thioesters
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Fig 7.12 Coenzyme A
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Thiamine Pyrophosphate (TPP)
• TPP is a derivative of thiamine (Vitamin B1)
• TPP participates in reactions of:
(1) Decarboxylation
(2) Oxidative decarboxylation
Fig 7.14 Thiamine
(Vitamin B1) and TPP
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Pyridoxal Phosphate (PLP)
• PLP is derived from Vit B6 family of vitamins
• Vitamin B6 is phosphorylated to form PLP
• PLP is a prosthetic group for enzymes catalyzing reactions
involving amino acid metabolism (isomerizations,
decarboxylations, side chain eliminations or replacements)
Fig 7.16 B6 Vitamins
and pyridoxal
phosphate (PLP)
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Fig 7.18 Mechanism of transaminases
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Biotin
(Why you shouldn’t eat raw eggs!)
• Biotin is required in very small amounts because it is available
from intestinal bacteria. Avidin (egg protein) binds biotin very
tightly and may lead to a biotin deficiency (cooking eggs
denatures avidin so it does not bind biotin)
• Enzymes using biotin as a prosthetic group catalyze :
(1) Carboxyl-group transfer reactions
(2) ATP-dependent carboxylation reactions
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Fig 7.24 Pterin, folate and tetrahydrofolate (THF)
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Abbreviated structure of cobalamin coenzymes
Fig 7.27
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Fig 7.28 Intramolecular rearrangements
catalyzed by adenosylcobalamin enzymes
(a) Rearrangement of an H and substituent X on an
adjacent carbon
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Fig 7.30 Formation of vitamin A
from b-carotene
Retinoic acid is a hormone that regulates gene expression in skin
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Vitamin D
• A group of related lipids involved in control of
Ca2+ utilization in humans
• Fig 7.31 Vitamin D3 and 1,25-dihydroxycholecalciferol
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Vitamin D deficiency causes rickets
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Vitamin E (a-tocopherol)
• A reducing reagent that scavenges oxygen and
free radicals
• May prevent damage to fatty acids in membranes
Fig 7.32 Vitamin E (a-tocopherol)
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Fig 7.32 (a) Structure of vitamin K
(b) Vit K-dependent carboxylation
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Warfarin is an anticoagulant
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