This document discusses enzyme regulation and the roles of cofactors and vitamins in enzyme function. It explains that enzymes are regulated through genetic control, covalent modification, and feedback inhibition. Coenzymes, which include vitamins and metal ions, are required for many enzyme reactions. Deficiencies in water-soluble vitamins can result since they are not stored, while fat-soluble vitamin excesses can be toxic. The roles of specific vitamins as coenzymes are outlined.

1. ENZYME REGULATION

2.  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

3.  Zymogens (proenzymes) are inactive forms of enzymes
 They are activated by removal of peptide sections
 For example, proinsulin is converted to insulin by
removing a 33-amino acid peptide chain

4.  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

5.  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)

6.  In feedback control, a product acts as a negative regulator
 When product concentration is high, it binds to an
allosteric site on the first enzyme (E1) in the sequence, and
production is stopped
 When product concentration is low, it dissociates from E1
and production is resumed
 Feedback control allows products to be formed only when
needed

7.  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

8.  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

9.  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

10.  Coenzymes are small organic molecules that are often
required to 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

11.  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

12.  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

13.  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
α-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

14.  Riboflavin is made of the sugar alcohol ribitol and 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
N
HH3C
H3C
CH2 CH CH CH CH2 OH
OHOHOH
O
O
D-Ribitol

15.  Niacin is part of the coenzyme nicotinamide adenine
dinucleotide (NAD+
) and NADP+
(P = phosphate)
 NAD+
and NADP+
are used in redox reactions involving
carbohydrates, 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)

16.  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
HO CH2 C CH C N CH2 CH2 C OH
O
H
OH OCH3
CH3

17.  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 the decarboxylation of carboxylic acids
 A deficiency of pyridoxine may lead to dermatitis,
fatigue and anemia
 Dietary sources include fish, meat, nuts, whole grains
and spinach

18.  Cobalamin consists of
four pyrrole rings with a
Co2+
 It is a coenzyme involved
in the 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)

19.  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
for collagen 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, bell
peppers, broccoli and cabbage
O
CHOH
CH2OH
OHHO
O

20.  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,
poor growth, 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, are
inhibitors of the enzyme that converts folic acid to THF
- these are used as anti-cancer drugs, especially for
leukemias

21.  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,
depressed immune 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 CH3
H3C CH3
H3C
CH3 CH3
CH2OH
H3C CH3
CH3
Beta-carotene
Retinol (vitamin A)

22.  Vitamin D (D3) is synthesized from 7-dehydrocholesterol
in skin exposed to sunlight
 It regulates the absorption of phosphorus and calcium
during bone growth
 A deficiency in vitamin D can result in weakened bones
 Dietary sources include cod liver oil, egg yolk, and
vitamin D enriched foods (such as milk)

23.  Vitamin E (α-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
beta forms (enantiomers)
- only the alpha form can be utilized by our cells
O
CH3
HO
H3C
CH3
CH3
CH3
CH3 CH3 CH3

24.  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 for
blood clotting
 A deficiency of vitamin K can lead to extended bleeding
from 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)