Transcript Chapter 7 ( part 1) - Nevada Agricultural Experiment
Chapter 7 (part 1) Cofactors
Cofactors
• Cofactors are organic or inorganic molecules
that are required for the activity of a certain conjugated enzymes
• Apoenzyme = enzyme (-) cofactor • Holoenzyme = enzyme (+) cofactor • Inorganic cofactors – essential ions • Organic cofactors – coenzymes
Essential Ion Cofactors
• Activator ions – bind reversibly to enzyme and
often participate in substrate binding.
• Metal ions of metalloenzymes – cations that are
tightly bound to enzyme and participate directly in catalysis (Fe, Zn, Cu, Co).
• Metal activated enzymes – require or are
stimulated by addition of metal ions (i.e. Mg 2+ , is required by many ATP requiring enzymes)
Metal ions can function as electrophiles in active site
Zinc protease (angiotensin converting enzyme)
Coenzymes
Cosubstrates - altered in rxn and regenerated to original structure in subsequent rxn - disassociated from active site - shuttle chemical groups among different enzyme rxns.
Prosthetic groups - remains bound to enzyme - must return to original form Both cosubstrates and prosthetic groups supply reactive groups not present on amino acid side chains
Coenzymes
• Metabolite coenzymes – synthesized from
common metabolites
• Nucleoside triphosphates – (ATP) can donate
phosphates, pyrophosphates, adenosyl grroups
• S-adenosylmethionine (SAM) – donates methyl
groups
• Nucleotide sugars (uridine diphosphate glucose =
UDP-glucose) - transfer sugars in carbohydrate metabolism
Vitamin derived coenzymes
• Must be obtained from diet • Synthesized by microorganisms and
plants
• Vitamin deficiencies lead to disease
state
• Most vitamins must be enzymatically
transformed to function as a coenzyme
Vitamin Ascorbic acid (C) Niacin Riboflavin (B 2 ) Thiamin (B 1 ) Pyridoxal (B 6 ) Biotin Folate Cobalamin (B 12 ) Vitamin A Vitamin K Pantothenate (B 3 )
Vitamins
Coenzyme not a coenzyme NAD(P)+/NAD(P)H FMN & FAD Thiamin-pyrophosphate Pyridoxal phosphate Biotin Tetrahydrafolate adenosyl-and methylcobalamin Retinal Vitamin K Coenzyme A
Niacin (nicotinic acid)
O O C C OH NH 2 N NICOTINIC ACID (NIACIN) N NICOTINAMIDE • Deficiencies lead to pellagra (dermatitis,
diarrhea, dementia)
• Required in relatively high amounts compared to
other vitamins
• Not true enzyme because can be synthesized
from tryptophan in the liver
Nicotinamide Coenzymes
H C O NH 2 C O C O OH NH 2 N O PO 2 O H 2 C PO 2 O O OH CH 2 O N OH N NH 2 N N
H
N NICOTINIC ACID (NIACIN) C O NH 2 N NICOTINAMIDE
H H
N R OXIDIZED N R REDUCED OH OH(OPO 3 ) C O NH 2
reactions
NAD
+
/ NADP
+
• Serve as cofactors in oxidation/reduction • Act as co-substrates for dehydrogenases • Reduction of NAD
+ /NADP + and oxidation of NADH/NADPH occurs 2 e- at a time.
• Function in hydride ion transfer • Rxns forming NADH/NADPH are catabolic • NADH is coupled with ATP production in
mitochondria
• NADPH is an impt reducing agent in
biosynthetic reactions
• Reduced forms (NADH/NADPH) absorb light at
340 nm, oxidized forms (NAD + /NADP + ) do not
Riboflavin (B2)
• Water soluble vitamin • Severe deficiencies lead to growth retardation, reproductive problems and neural degeneration • Meat, dairy products and dark green vegetables, legumes and grains are good sources
FMN/FAD
FAD and FMN can transfer electrons one or two at a time
Quinone form Hydroquinone form semiquinone form
Thiamin
•Thiamin is the first Vitamin discovered (Vital
amine = Vitamin)
•Deficiencies lead to disease called Beriberi
(neurological disorders, heart problems, anorexia)
•Beriberi prevealent in undeveloped countries where
polished grains make up the majority of the diet.
•Associated with alcohol related disorders
(Wernickes-Korskofff syndrome – memory loss, unstable walk)
Thiamin pyrophosphate
•Serves as a cofactor in decarboxylation rxn of keto
acids
•Also functions as a prosthetic group in
transketolases (catalyze the transfer of two carbon units in carbohydrate metabolism)
Thiazolium ring is the chemically active part of TPP
Ylid = a molecule with opposite charges on adjacent atoms
HOH 2 C H 2 C OH
Pyridoxal
HC O O O HOH 2 C HOH 2 C H 2 C NH 3 O N H PYRIDOXINE CH 3 N H PYRIDOXAL CH 3 N H CH PRYIDOXAMINE 3 O O O P O O H 2 C HC O N CH 3 H PYRIDOXAL 5' PHOSPHATE O NH 3 O P O O H 2 C H 2 C O N H CH PYRIDOXAMINE 5' PHOSPHATE 3
PYRIDOXAL-PHOSPHATE
•Important in amino acid metabolism •Bound to enzyme as a Schiff base thru rxn with lysine O - H2O R C H + NH2 R 2 R C H N R 2 + H2O ALDEHYDE AMINE SCHIFF BASE • PLP functions in transamination, decarboxylation, racemization, isomerization, side-chain elimination rxns involving amino acids
PLP in transamination reaction
PLP in amino acid decarboxylation reaction