103 lecture ch21b.ppt
TRANSCRIPT
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Regulation of Enzyme Activity
Enzyme activity must be regulated so that the proper levels of
products are produced at all times and places
This control occurs in several ways:
- biosynthesis at the genetic level
- covalent modification after biosynthesis
- regulatory enzymes
- feedback inhibition
A common covalent enzyme modification is the addition or
removal of a phosphate group
- under high-energy conditions (high ATP and low ADP),phosphorylation is favored
- under low-energy conditions (low ATP and high ADP),
dephosphorylation is favored
- this regulates the balance between biosynthesis and catabolism
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Zymogens Zymogens (proenzymes) are inactive forms of enzymes
They are activated by removal of peptide sections
For example, proinsulin is converted to insulin by removinga 33-amino acid peptide chain
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Digestive Enzymes Digestive enzymes are produced as zymogens, and are
then activated when needed
Most of them are synthesized and stored in the pancreas,and then secreted into the small intestine, where they are
activated by removal of small peptide sections
The digestive enzymes must be stored as zymogens
because otherwise they would damage the pancreas
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Allosteric Enzymes
An allosteric enzyme binds a regulator molecule at a
site other than the active site (an allosteric site)
Regulators can be positive or negative:
- a positive regulator enhances the binding of
substrate and accelerates the rate of reaction.
- a negative regulator prevents the binding of the
substrate to the active site and slows down the rate of
reaction (non-competitive inhibition)
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Feedback Control In feedback control, a product acts as a negative regulator
When product concentration is high, it binds to an allosteric siteon the first enzyme (E
1) in the sequence, and production is
stopped
When product concentration is low, it dissociates from E1 andproduction is resumed
Feedback control allows products to be formed only when needed
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Enzyme Cofactors
A simple enzyme consists only of protein in its active form
Other enzymes are active only when they combine with
cofactors such as metal ions or small molecules- a cofactor that is a small organic molecule, such as a
vitamin, is called a coenzyme
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Metal Ions as Cofactors Many enzymes require a metal ion to carry out catalysis
Metal ions in the active site are attached to one or more
amino acid side-chains The metal ions have various functions, such as electron
exchange and substrate stabilization
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A Zinc Carboxypeptidase A Zn2+ ion in the active site of carboxypeptidase A promotes
hydrolysis of a C-terminal amino acid from a polypeptide by
interacting with the carbonyl oxygen The Zn2+ activates the carbonyl in a similar way as an acid catalyst
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Functions of Coenzymes
Coenzymes are small organic molecules that are often requiredto prepare the active site for proper substrate binding and/or
participate in catalysis Because they are not destroyed during the reaction, coenzymes
are only required in small quantities
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Water Soluble Vitamins Vitamins are organic molecules that are essential for metabolism,
but can not be biosynthesized; they must be consumed in the diet
Many coenzymes come from water-soluble vitamins
Water soluble vitamins are not stored in the body, and so should
be consumed daily
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Fat Soluble Vitamins
Fat soluble vitamins are not used as coenzymes
However, they are important in vision, bone formation,
antioxidants, and blood clotting
Fat soluble vitamins are stored in the body, so should not
be consumed in excess, as they can be toxic at high levels
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Thiamin (Vitamin B1)
Thiamin was the first B vitamin identified, and is part of the
coenzyme thiamin pyrophosphate (TPP)
TPP coenzyme is required by enzymes for decarboxylation of-keto carboxylic acids
A deficiency of thiamin results in beriberi (fatigue, weight loss,
and nerve degeneration)
Dietary sources include whole grains, milk products and yeast
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Riboflavin (Vitamin B2)
Riboflavin is made of the sugar alcohol ribitoland flavin
It is part of the coenzymes flavin adenine dinucleotide
(FAD) and flavin mononucleotide (FMN)
FAD and FMN are used in redox reactions involving
carbohydrates, proteins and fats
Riboflavin is needed for good vision and healthy skin, and
a deficiency can lead to cataracts and dermatitis Dietary sources include green leafy vegetables, whole
grains, milk products, chicken, eggs and peanuts
N
N N
NHH3C
H3C
CH2 CH CH CH CH2 OH
OHOHOH
O
O
D-Ribitol
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Niacin (Vitamin B3)
Niacin is part of the coenzyme nicotinamide adenine
dinucleotide (NAD+) and NADP+ (P = phosphate)
NAD+ and NADP+ are used in redox reactions involvingcarbohydrates, proteins and fats
A deficiency of niacin can result in dermatitis, muscle
fatigue and loss of appetite
Dietary sources include meats, rice, and whole grains
N
OH
O
Niacin (Nicotinic Acid)
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Pantothenic Acid (Vitamin B5)
Pantothenic acid is part of coenzyme A
Coenzyme A is involved in energy production, conversion
of lipids and amino acids to glucose and synthesis of
cholesterol and steroid hormones
A deficiency of pantothenic acid can result in fatigue,
retarded growth, cramps, and anemia
Dietary sources include salmon, meat, eggs, whole grains,
and vegetables
O CH2 C CH C N CH2 CH2 C OH
O
H
OH OCH3
CH3
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Pyridoxine (Vitamin B6)
Pyridoxine and pyridoxal are two forms of vitamin B6
They are converted to the coenzyme pyridoxal phosphate (PLP)
PLP is involved in the transamination of amino acids and thedecarboxylation of carboxylic acids
A deficiency of pyridoxine may lead to dermatitis, fatigue and
anemia
Dietary sources include fish, meat, nuts, whole grains andspinach
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Cobalamin (Vitamin B12)
Cobalamin consists of four
pyrrole rings with a Co2+
It is a coenzyme involved inthe transfer of methyl
groups, acetyl choline
synthesis and red blood cell
production A deficiency in vitamin B12
can lead to pernicious
anemia and nerve damage
Dietary sources include
beef, chicken, fish and milk
products (strict vegans
should take B12
supplements)
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Ascorbic Acid (Vitamin C)
Ascorbic acid is a very polar hydroxy ester that is a weak acid
It is involved in the synthesis of hydroxyproline and
hydroxylysine, two modified amino acids that are required forcollagen synthesis
A deficiency of vitamin C can lead to slow-healing wounds,
weakened connective tissue, bleeding gums and anemia
Dietary sources include berries, citrus fruits, tomatoes, bellpeppers, broccoli and cabbage
OCHOH
CH2OH
OHHO
O
F li A id (F l )
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Folic Acid (Folate) Folic acid (folate) consists of pyrimidine, p-aminobenzoic acid
(PABA) and glutamate
It forms the coenzyme THF used in the synthesis of nucleic acids
A deficiency can lead to abnormal red blood cells, anemia, poorgrowth, hair loss and depression
Dietary sources include green leafy vegetables, beans, meat,seafood, yeast, asparagus and whole grains
Some derivatives of folic acid, such as methotrexate, areinhibitors of the enzyme that converts folic acid to THF
- these are used as anti-cancer drugs, especially for leukemias
Vit i A
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Vitamin A Vitamin A can exist as an alcohol (retinol), an aldehyde
(retinal) or a carboxylic acid (retinoic acid)
In the retina of the eye, retinol undergoes cis-trans isomeration
as part of photoreception Vitamin A is also involved in synthesis of RNA and
glycoproteins
A deficiency in vitamin A can lead to night blindness, depressedimmune response and growth inhibition
Dietary sources include yellow and green fruits and vegetables Beta-carotenes are converted to vitamin A in the liver
H3C CH3
CH3
CH3 CH3
CH3 CH3H3C CH3
H3C
CH3 CH3
CH2OHH3C CH3
CH3
Beta-carotene
Retinol (vitamin A)
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Vitamin D
Vitamin D (D3) is synthesized from 7-dehydrocholesterol in
skin exposed to sunlight
It regulates the absorption of phosphorus and calcium duringbone growth A deficiency in vitamin D can result in weakened bones
Dietary sources include cod liver oil, egg yolk, and vitamin Denriched foods (such as milk)
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Vitamin E
Vitamin E (-tocopherol) acts as an antioxidant in cells Not much is know about its mechanism, but it may prevent
the oxidation of unsaturated fatty acids A deficiency of vitamin E can lead to anemia
Dietary sources include meat, nuts, vegetable oils, whole
grains, and vegetables
Synthetic vitamin E is a mixture of the alpha and betaforms (enantiomers)
- only the alpha form can be utilized by our cells
O
CH3
HO
H3C
CH3
CH3
CH3
CH3 CH3 CH3
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Vitamin K
Vitamin K1 (in plants) has a saturated side chain
Vitamin K2 (in animals) has a long unsaturated side chain
Vitamin K2 is needed for the synthesis of zymogens forblood clotting
A deficiency of vitamin K can lead to extended bleedingfrom small cuts and increased bruising
Dietary sources include meat, spinach and cauliflower
CH3
CH3
O
O CH3 CH3
Vitamin K1 (phylloquinone)
CH3
CH3
O
O CH3 CH3
Vitamin K2 (menaquinone)