103 Lecture Ch21b.ppt

7/29/2019 103 Lecture Ch21b.ppt

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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)

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103 Lecture Ch21b.ppt