1 Part 7 Coenzymes-Dependent Enzyme Mechanisms Professor A. S. Alhomida Disclaimer The texts, tables and images contained in this course presentation are

1

Part 7 Coenzymes-Dependent Enzyme

MechanismsProfessor A. S. Alhomida

Part 7 Coenzymes-Dependent Enzyme

MechanismsProfessor A. S. Alhomida

Disclaimer• The texts, tables and images contained in this course presentation

are not my own, they can be found on: – References supplied– Atlases or– The web

King Saud University

College of Science

Department of Biochemistry

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Lipid-Soluble Vitamins

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Fat-Soluble Vitamins

• Vitamins A, D, K and E are the fat-soluble vitamins

• Excessive use of vitamins A and K can lead to toxicities

• Fat-soluble vitamins tend to be stored in fatty tissues of the body and in the liver

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• Absorption and transport of fat soluble vitamins is closely associated with lipids(1) Require esterases, lipase and colipase

(2) Require bile salts for micelle formation

(3) Require incorporation into CMs for transport

• Stored in lipid– Amount varies widely

Lipid-Soluble Vitamins

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Vitamin A

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Vitamin A

• Exits in 3 forms:(1) All trans-retinol

(2) Long chain fatty acyl ester of retinol, RE (main storage form)

(3) Retinal (the active form in the retina)

• Retinoic acid (RA) is also considered to be physiologically active

• Provitamin A or carotene can be converted to retinol in vivo

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Structure of Vitamin A

• Vitamin A contains 5 conjugated double bonds which are

• key to some biological actions

• Isolated in impure form by McCollum in 1915 CH3

CH3H3CCH3

CH2OH

CH3

VITAMIN A (RETINOL)

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CH3CH3

H3C

CH3

H3C CH3

H3C

CH3CH3

CH3

-carotene

CH3CH3

H3C

CH3

CH3

OH

CH3CH3

H3C

CH3

CH3

O

H

liverO2

retinal (active form in vision)

CH3CH3

H3C

CH3

CH3

O

COOH

CH3CH3

H3C

CH3

CH3

retinoic acid ("hormonally-active form")R

O

vitamin A acetate (R = CH3)vitamin A palmitate (R = C16H33

retinol (from diet)

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Vitamin A

• Preformed vitamin A– Retinol (alcohol) and retinal (aldehyde)

• Retinoic acid is derived from retinal

• Provitamin A– Carotenoids that can be converted to retinol

• Sources– Free retinol (all trans) not present in food

• Present as precursor fatty acid esters– Retinyl palmitate– Animal products including egg yolks, butter, whole

milk products, liver and fish liver oils

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Vitamin A (and -carotenoids)

• Functions:– Normal vision– Protects from

infections– Regulates immune

system– Antioxidant

(carotenoids)

• Food sources:– Liver– Fish oil– Eggs– Fortified milk or other

foods– Red, yellow, orange,

and dark green veggies (carotenoids)

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Vitamin A Sources

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Vitamin A, Cont’d

• Sources (Continued)– Carotenoids

• Red, orange and yellow pigments made by plants• -carotene is pigment with greatest Vit A activity• 12 g -carotene or 24 g other carotenoids = 1 retinol

activity equivalent (RAE)

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Metabolism of Vitamin A

• Digestion and Absorption – Often complexed to protein

• Release requires pepsin in stomach and proteases in small intestine (SI)

– Release from fatty acids• Esterases and lipases

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• Digestion and Absorption– Released carotenoids and retinols in SI are

incorporated into micelles– Vitamin A diffuses into enterocyte in proximal SI– 70 to 90% of retinol absorbed– 20 to 50% of carotenoids absorbed

• Within enterocyte– -carotene can be converted to retinal and then

reduced to retinol or oxidized to retinic acid (RA)– Retinol is acetylated (reesterifed) to retinyl ester (RE)

Metabolism of Vitamin A, Cont’d

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• Within enterocyte– Primary pathway for re-esterification involves

cellular retinol-binding protein (CRBP) II• CRBP II binds both retinal and retinol

– Directs the reduction of retinal to retinol

– Directs the esterification of retinol to RE» Lecithin retinol acyl transferase (LRAT) transfers acyl group

to form retinyl palmitate

• Non-specific protein may also bind retinol when in high amounts

– Re-esterification requires acyl-CoA retinol acyl transferase


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• Within enterocyte– RE + small amount of unesterified retinol and

unchanged carotenoids are incorporated into CM along with

• Cholesterol esters, phospholipid, TGs, apoproteins

– CMs enter lymphatic system and later general circulation

– Some retinal may be irreversibly converted to RA which enters portal blood and binds to albumin


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• Transport– CMs

• Removal of RE, retinol and carotenoids on route to liver by extrahepatic tissues

– Bone marrow, blood cells, spleen, adipose, muscle, lungs, kidneys

– CM remnants removed by liver

• In Liver– Carotenoids can follow 1 of 3 routes

• Cleavage to retinol, incorporated into VLDL, stored in liver


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• In Liver– RE

• Hydrolyzed to free retinol• Retinol binds with CRBP• Enzymatic metabolism

– Esterification by LRAT or ARAT

– Oxidation of retinol to retinal

– Phosphorylation of retinol to retinyl phosphate

– Retinol not metabolized or transported out– Stored as retinly ester primarily in stellate cells


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• Retinol Export from Liver– Dependent upon synthesis and secretion of

retinol-binding protein (RBP) by parenchymal cells in liver

– RBP binds retinol (from stellate cells) (holo-RBP)– Complex secreted in plasma

• In plasma– Holo-RBP interacts with transthyretin (TTR)– RBP-TTR complex circulates in plasma– Retinol can be taken up from complex


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• Uptake of retinol by cells– Retinol removed leaving behind RBP-TTR– RBP-TTR then dissociate

• Apo-RBP catabolized by kidney

• Retinoic acid is made by individual cells– In cytoplasm, retinal binds to cellular retinoic acid-

binding proteins (CRABPs)• Function in capacity similar to CRBPs

– Prevent catabolism and direct usage


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• Visual cycle– Retinol transported to retina via the RBP-TTR

complex• Retinol taken up by photoreceptor rod cells• Involves two proteins specific to retina and CRALBP and

IRBP (direct reactions) in addition to CRBP and CRABP

– Within retina• Retinol may be converted to RE and stored• RE is hydrolyzed to retinol as needed• Retinol is oxidized to all-trans retinal• All-trans retinal is converted to 11-cis retinal

Vision and Vitamin A

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• Within retina– 11-cis retinal binds the protein opsin forming

rhodopsin– Rod cells with rhodopsin detect small amounts of

light and are important in night vision– When light hits rhodopsin, it breaks down in a

series of reactions (bleached-loses color)– Upon degradation of rhodopsin, all trans retinal is

is regenerated– Processes leads to an electrical signal to optic

nerve (light has hit rhodopsin)

Vision and Vitamin A, Cont’d

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• Photoreception is the function of two specialized cell types: rods and cones

• Both types of cells contain a photosensitive compound called opsin– In rod cells opsin is called scotopsin and the

receptor is called rhodopsin or visual purple– Rhodopsin is a serpentine receptor imbedded in

the membrane of the rod cell; it is a complex between scotopsin and 11-cis retinal


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• Intracellularly, rhodopsin is coupled to a G-protein called transducin

• When rhodopsin is exposed to light, it is bleached releasing the 11-cis-retinal from opsin

• Absorption of photons by 11-cis-retinal triggers the conversion to all-trans-retinal (one important conformational intermediate is metarhodopsin II); also there is a change in conformation of the photoreceptor


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Bleach and Recycle

• The "bleach and recycle" process is utilized within the retina to ensure that the chromophore, 11-cis retinal, is present within opsin molecules in sufficient quantities to allow phototransduction to occur

• To understand the process, we must look first at where the retina gets its vitamin A (retinol)

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• These transformations activate a phosphodiesterase (which hydrolyzes c-GMP to GMP)

• c-GMP is necessary to maintain the Na+ channels in the rods in the open conformation

• With a decrease in c-GMP, there occurs a closure of the Na+ channels, which leads to hyperpolarization of the rod cells with concomittant propagation of nerve impulses to the brain

Vision and the Role of Vitamin A, Cont’d

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• Within retina– Visual cycle is complete when all-trans retinal is

converted back to 11-cis retinal and bound once again to rhodopsin

– These final steps are necessary in order to see in dim light

– With every cycle, small amounts of vitamin A are catabolized and must be replaced

Functions of Vitamin A, Cont’d

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Vitamin A and Rhodopsin

http://www.chm.bris.ac.uk/webprojects2003/rogers/998/fpAnimswapImgFP1

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H3C CH3

CH3

CH3

H3C

N

H

N

N

O

H

H

11-cis

Schiff's base

lysine chain of opsin

CH3H3C

H3C

CH3

N

CH3

N

NO

H

H

H

1. light2. isomerization of retinal3. change in shape of rhodopsin

11-trans retinal

signal transduction nerve impulse

RHODOPSIN

(11-cis retinal + opsin)

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Visual Cycle

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Visual Cycle, Cont’d

• The visual cycle is the biological conversion of a photon into an electrical signal in the retina

• This process occurs via G-protein coupled receptors (GPCR) called opsins which contain the chromophore 11-cis retinal

• 11-cis retinal is covalently linked to the opsin receptor via a Schiff base forming a retinylidene protein

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• When struck by a photon, 11-cis retinal undergoes photoisomerization to all-trans retinal which changes the conformation of the opsin GPCR leading to signal transduction cascades which causes closure of a cyclic GMP-gated cation channel, and hyperpolarization of the photoreceptor cell

• Following isomerization and release from the opsin protein, all-trans retinal is reduced to all-trans retinol and travels back to the retinal pigment epithelium to be "recharged“


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• It is first esterified by lecithin-retinol acyltransferase (LRAT) and then converted to 11-cis retinol by the isomerohydrolase RPE65

• Finally, it is oxidized to 11-cis retinal before traveling back to the rod outer segment where it can again be conjugated to an opsin to form a new, functional visual pigment (rhodopsin)


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G Protein-coupled Receptor (GPCR)

• Rhodopsin is a transmembrane protein consisting of 7 membrane-spanning helices, that are interconnected by extracellular and cytoplasmic loops

• As a chromophore, it has covalently bound in its inactive dark state 11-cis retinal, which isomerizes after photon absorption to an all-trans geometry

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• Cellular differentiation– Retinoic acid (RA)

• Functions as a hormone to affect gene expression

– RA or 9-cis RA taken into nucleus bound to CRABP

– In nucleus• RA or 9-cis RA binds to RAR (RA Receptors)• 9-cis RA binds to RXR (Retinoid Receptors)

• RAR-RXR dimerization permits interaction with specific nucleotide sequences of DNA (genes)

– Regulates transcription to RNA and translation to protein

Functions of Retinic Acid (RA)

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• Acts as a morphogen in embryonic development (may signal morphogenesis- evolution and development of form)

• Maintenance of normal structure and function of epithelial cells– Epithelial cells found in lungs, trachea, skin,

cornea and GI tract• Directs the differentiation of keratinocytes into mature

epidermal cells• Also directs keratin synthesis• Directs differentiation of epithelial keratinizing cells in

mucus-secreting cells in vitro

Functions of Retinic Acid (RA), Cont’d

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CH3

CH3H3CCH3

COOH

CH3

RETINOIC ACID (RETIN A)

• RA is important for cellular differentiation;

• It controls cellular growth – particularly cell growth

• Used in the treatment of acne; also used as an anti-wrinkle agent

• Also used orally to treat acute promyelocytic leukemia (APL)

Functions of Retinic Acid (RA), Cont’d

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• Growth– Vitamin A deficiency results in poor growth– Administration of ROH or RA can stimulate

impaired growth• Particularly growth of epithelial cell• Stimulate the # of specific receptors for GF

• ROH essential for reproductive process• Immune system

– Needed for T-lymphocyte function, antibody response, phagocytosis


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• Bone development– Vitamin A deficiency results in excessive

deposition of bone by osteoblasts and reduced number of osteoclasts

• Antioxidants (-Carotene)– Possess ability to react with and quench

(inactivate) free-radical reactions in membrane systems and possibly in solution (plasma/cytoplasm)

– Prevent oxidation of LDL-C?


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• Toxicity– Joint pain– Dry skin – Fatigue– HA, weakness– Nausea– Supplements of pre-

formed active Vit A

Vitamin A – Problems

• Deficiency– Night blindness– Blindness– Infectious diseases

(especially measles)

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Additional Role of Retinol

• Retinol also functions in the synthesis of certain glycoproteins and mucopolysaccharides necessary for mucous production and normal growth regulation

• This is accomplished by phosphorylation of retinol to retinyl phosphate which then functions similarly to dolichol phosphate

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• It is a modification of RA

• It contains a 13-cis double bond and is orally effective

• It is used in the treatment of severe acne

CH3

CH3H3CCH3 CH3

COOH

ISOTRETINOIN (ACCUTANE)

Isotretinoin (Accutane)

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• An aromatic analog of RA

• Its orally effective and used in the management and treatment of psoriasis

CH3O CH3

H3C

CH3 CH3 CH3

COOH

ACITRETIN (SORIATANE)

Acitrein (Soriatane)

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Etretinate (Tegison)

• Esterified form of acitretin; also used orally in the

• treatment of recalcitrant psoriasis; 10 and 25 mg capsules

CH3

H3C

CH3O CH3

CH3 CH3

O

OC2H5

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Alitretinoin (Panretin)

• Currently used as a 0.1% gel for the topical treatment

• of cutaneous lesions in patients with AIDS-related

• Kaposi sarcoma

CH3H3C

CH3

CH3

CO2H

CH3

9-cis-retinoic acid (Alitretinoin)

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• Indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma

• Usually the patients receiving this drug have failed to respond to other treatment protocols

• Pregnancy (Category X drug)

CH3

H3C CH3

H3C CH3

COOH

CH2

Bexarotene (Targretin)

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Adapalene (Differin)

OCH3

HO2C

Adapalene

• Used as a 0.1% gel in the treatment of acne vulgaris

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Tazarotene (Tazorac)

• Topical treatment of patient with facial acne vulgaris of

• Mild to moderate severity; gel 0.05%, 0.1%

N C C

S

H3C CH3

EtO2C

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Nutrient-Nutrient Interactions

• Vitamin E– Needed for cleavage of -carotene into retinal– May protect substrate and product from oxidation

• Excess Vitamin A– May inhibit both Vitamin E and K absorption

• Protein status– Transport and use of the vitamin depends on

several vitamin A binding proteins

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Vitamin D

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Vitamin D Forms

• Vitamin D1: Molecular compound of ergocalciferol with lumisterol, 1:1

• Vitamin D2: Ergocalciferol or calciferol (made from ergosterol)

• Vitamin D3: Cholecalciferol (made from 7-dehydrocholesterol in the skin)

• Vitamin D4: 22-Dihydroergocalciferol • Vitamin D5: Sitocalciferol (made from 7-

dehydrositosterol)

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• In most mammals, including humans, D3 is more effective than D2 at increasing the levels of D hormone in circulation; D3 is at least 3-fold, and likely closer to 10-fold, more potent than D2

• In some species, such as rats, vitamin D2 is more effective than D3

• Both D2 and D3 are used for human nutritional supplementation, and pharmaceutical forms

Vitamin D Forms, Cont’d

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Vitamin D

• There are two major forms:(1) Vitamin D2 (ergocalciferol)

(2) Vitamin D3 (cholecalciferol)

• The term vitamin D also refers to metabolites and other analogs of these substances

• Vitamin D3 is produced in skin exposed to sunlight, specifically ultraviolet B radiation

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Biosynthesis of Vitamin D

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Biosynthesis of Vitamin D, Cont’d

• Photochemical synthesis of vitamin D3 (cholecalciferol) occurs cutaneously where pro-vitamin D3 (7-dehydrocholesterol) is converted to pre-vitamin D3 (pre-D3) in response to ultraviolet B (sunlight) exposure

• Vitamin D3, obtained from the isomerization of pre-vitamin D3 in the epidermal basal layers or intestinal absorption of natural and fortified foods and supplements, binds to vitamin D-binding protein (DBP) in the bloodstream, and is transported to the liver

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• D3 is hydroxylated by liver 25-hydroxylases (25-OHase)

• The resultant 25-hydroxycholecalciferol (25(OH)D3) is 1-hydroxylated in the kidney by 25-hydroxyvitamin D3-1-hydroxylase (1-OHase)

• This yields the active secosteroid 1,25(OH)2D3 (calcitriol), which has different effects on various target tissues


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• The synthesis of 1,25(OH)2D3 from 25(OH)D3 is stimulated by parathyroid hormone (PTH) and suppressed by Ca2+, Pi and 1,25(OH)2D3 itself

• The rate-limiting step in catabolism is the degradation of 25(OH)D3 and 1,25(OH)2D3 to 24,25(OH)D3 and 1,24,25(OH)2D3, respectively, which occurs through 24-hydroxylation by 25-hydroxyvitamin D 24-hydroxylase (24-OHase)


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• 24,25(OH)D3 and 1,24,25(OH)2D3 are consequently excreted

• The main effects of 1,25(OH)2D3 on various target tissues are highlighted above

• Vitamin D3 can be endogenously produced and that as long as the animal (or human) has access on a regular basis to sunlight there is no dietary requirement for this vitamin


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Biochemical Functions of Vitamin D

1. Vitamin D regulates the calcium and phosphorus levels in the blood by promoting their absorption from food in the intestines, and by promoting re-absorption of calcium in the kidneys

2. It promotes bone formation and mineralization and is essential in the development of an intact and strong skeleton

3. Although, at very high levels it will promote the resorption of bone

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Biochemical Functions of Vitamin D, Cont’d

4. It inhibits parathyroid hormone secretion from the parathyroid gland

5. Vitamin D affects the immune system by promoting immunosuppression, phagocytosis, and anti-tumor activity

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Biochemistry of Vitamin D

• Vitamin D is a prohormone, meaning that it has no hormone activity itself, but is converted to the active hormone 1,25-D through a tightly regulated synthesis mechanism

• Production of vitamin D in nature always appears to require the presence of some UV light

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Biochemistry of Vitamin D, Cont’d

• Even vitamin D in foodstuffs is ultimately derived from organisms, from mushrooms to animals, which are not able to synthesize it except through the action of sunlight at some point in the synthetic chain

• For example, fish contain vitamin D only because they ultimately exist on calories from ocean algae which synthesize vitamin D in shallow waters from the action of solar UV

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• Vitamin D3 is produced photochemically in the skin from 7-dehydrocholesterol

• The highest concentrations of 7-dehydrocholesterol are found in the epidermal layer of skin

• The highest concentrations of 7-dehydrocholesterol are found in the epidermal layer of skin, specifically in the stratum basale and stratum spinosum


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• The production of pre-vitamin D3 is therefore greatest in these two layers, whereas production in the other layers is reduced

• The two most important factors that govern the generation of pre-vitamin D3 are the quantity (intensity) and quality (appropriate wavelength) of the UV irradiation


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• A critical determinant of vitamin D3 production in the skin is the presence and concentration of melanin

• Melanin functions as a light filter in the skin, and therefore the concentration of melanin in the skin is related to the ability of UV light to penetrate the epidermal strata and reach the 7-dehydrocholesterol-containing stratum basale and stratum spinosum


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• Under normal circumstances, ample quantities of 7-dehydrocholesterol (about 25-50 mg/cm² of skin) are available in human skin to meet the body's vitamin D requirements

• Melanin content does not alter the amount of vitamin D that can be produced


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• Individuals with higher skin melanin content will simply require more time in sunlight to produce the same amount of vitamin D as individuals with lower melanin content

• Melanin functions as a light filter in the skin, and therefore the concentration of melanin in the skin is related to the ability of UV light to penetrate the epidermal strata and reach the 7-dehydrocholesterol-containing stratum basale and stratum spinosum


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Mechanism Action of Vitamin D

• Once vitamin D is produced in the skin or consumed in food, it is converted in the liver and kidney to form 1,25(OH)2D (when "D" is used without a subscript it refers to either D2 or D3)

• The hormonally active form of vitamin D is released into the circulation, and by binding to a carrier protein in the plasma, vitamin D binding protein (VDBP), it is transported to various target organs

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• The hormonally active form of vitamin D mediates its biological effects by binding to the vitamin D receptor (VDR), which is principally located in the nuclei of target cells

• The binding of calcitriol to the VDR allows the VDR to act as a transcription factor that modulates the gene expression of transport proteins (such as TRPV6 and calbindin), which are involved in calcium absorption in the intestine

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• The Vitamin D receptor belongs to the nuclear receptor superfamily of steroid/thyroid hormone receptors, and VDR are expressed by cells in most organs, including the brain, heart, skin, gonads, prostate, and breast

• VDR activation in the intestine, bone, kidney, and parathyroid gland cells leads to the maintenance of calcium and phosphorus levels in the blood (with the assistance of parathyroid hormone and calcitonin) and to the maintenance of bone content

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• The VDR is known to be involved in cell proliferation, differentiation

• Vitamin D also affects the immune system, and VDR are expressed in several white blood cells including monocytes and activated T and B cells

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Deficiency of Vitamin D

• (1) Inadequate intake coupled with inadequate sunlight exposure, disorders that limit its absorption, conditions that impair conversion of vitamin D into active metabolites, such as liver or kidney disorders, or, rarely, by a number of hereditary disorders

• (2) It results in impaired bone mineralization, and leads to bone softening diseases, rickets in children and osteomalacia in adults, and possibly contributes to osteoporosis

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• The role of diet in the development of rickets was determined by Edward Mellanby between 1918–1920

• In 1921 Elmer McCollum identified an anti-rachitic substance found in certain fats could prevent rickets

• Because the newly discovered substance was the fourth vitamin identified, it was called vitamin D

Deficiency of Vitamin D, Cont’d

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• The 1928 Nobel Prize in Chemistry was awarded to Adolf Windaus, who discovered the steroid, 7-dehydrocholesterol, the precursor of vitamin D

• Vitamin D deficiency is known to cause several bone diseases including

• Rickets, a childhood disease characterized by impeded growth, and deformity, of the long bones


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• Osteomalacia, a bone-thinning disorder that occurs exclusively in adults and is characterised by proximal muscle weakness and bone fragility

• Osteoporosis, a condition characterized by reduced bone mineral density and increased bone fragility

• Prior to the fortification of milk products with vitamin D, rickets was a major public health problem


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• In the US, milk has been fortified with 10 g (400 IU) of vitamin D per quart since the 1930s, leading to a dramatic decline in the number of rickets cases

• Vitamin D malnutrition may also be linked to several chronic diseases such as high blood pressure, tuberculosis, cancer, periodontal disease, multiple sclerosis, chronic pain, depression, schizophrenia, seasonal affective disorder, and several autoimmune diseases including type1 diabetes


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Biological Functions of Vitamin D

• Calcium homeostasis – it is critical for the body to maintain the proper calcium level in the blood stream– Intestinal calcium absorption: acts as a signal to

tell intestinal cells to take up more calcium from the gut

– Bone calcium mobilization• Signals osteoclast (bone cells) to release calcium into

the blood stream in response to low calcium levels

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• Cellular differentiation – much less well understood – signal to bone marrow cells to change into other cells

leukemia cell

1,25(OH)2 vitamin D3

normal white blood cell

derived from bone marrow grows at the proper rate

high levels

Problem: 1,25(OH)2-D3 causes hypercalcemia

Biological Functions of Vitamin D, Cont’d

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Various analogs of vitamin D

• Potential use:– Anti-cancer agent– Immunosuppressive

OH

HO

synthetic analog of vitamin D

85

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Doxercalciferol (Hectorol)

• A synthetic vitamin D analog that undergoes in vivo metabolic activation to 1-a,25-dihydroxyvitamin D2

• Activation does not require involvement of the kidneys

• Used in hyperparathyroidism in patients undergoing chronic renal dialysis

• Initial dose 10 mcg orally 3 times per week

CH2

HO OH

CH3

H3C

CH3

DOXERCALCIFEROL (HECTOROL)

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HO

H OH

CH3

H

OH

PARACALCITOL (ZEMPLAR)

Paricalcitol (Zemplar)

• A synthetic vitamin D analog

• Indicated for the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure

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CH2

HO OH

CH3

H

H3COH

CALCIPOTRIENE (DOVONEX)

Calcipotriol (Dovonex)

• A vitamin D derivative approved for the treatment of psoriasis

• Receptor affinity is similar to that of calcitriol, but is less than 1% as active in regulating calcium metabolism

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Calcipotriene

• An analog of vitamin D3 with a modified side-chain containing a 24-OH group and a cyclopropyl group

• It binds strongly to the D3 receptor on keratinocytes in skin and it suppresses their proliferation (used in psoriasis)

• It has only about 0.5% of the activity of D3 on calcium and phosphorus metabolism

90

Dihydrotachysterol

• A reduction product of vitamin D2

• It is used in the management of hypoparathyroidism

• It has only 1/450th the antirachidic activity of vitamin D2

H3C

HO

CH3

Documents

1 Part 7 Coenzymes-Dependent Enzyme Mechanisms Professor A. S. Alhomida Disclaimer The texts, tables and images contained in this course presentation are