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Metabolism

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Title: Metabolism


1
Chapter 17
  • Metabolism An Overview
  • Biochemistry
  • by
  • Reginald Garrett and Charles Grisham

2
Metabolism
  • Metabolism represents the sum of the chemical
    changes that convert nutrients into energy and
    the chemically complex products of cells
  • Metabolism consists of literally hundreds of
    enzymatic reactions organized into discrete
    pathways
  • These pathways proceed in a stepwise fashion,
    transforming substrates into end products through
    many specific chemical intermediates
  • Metabolism is sometimes referred to as
    intermediary metabolism

3
Metabolism
  • The metabolism map can be viewed as a set of dots
    and lines
  • Intermediate as a black dot
  • Enzyme as a line
  • More than 1000 different enzymes and 500
    intermediates
  • About 80 of the intermediates connect to only
    one or two lines

Lines Dots
1 or 2 410
3 71
4 20
5 11
6 or more 8
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5
Outline of Chapter 17
  • Are There Similarities of Metabolism Between
    Organisms?
  • How Do Anabolic and Catabolic Processes Form the
    Core of Metabolic Pathways?
  • What Experiments Can Be Used to Elucidate
    Metabolic Pathways?
  • What Food Substances Form the Basis of Human
    Nutrition?
  • Special Focus Vitamins

6
17.1 Are There Similarities of Metabolism
Between Organisms?
  • Organisms show a marked similarity in their major
    metabolic pathways
  • All life descended from a common ancestral form
  • For example, Glycolysis, the metabolic pathway by
    which energy is released from glucose and
    captured in the form of ATP under anaerobic
    condition, is common to almost every cell

7
Living things exhibit metabolic diversity
  • Although most cells have the same basic set of
    central metabolic pathways, different cells are
    characterized by the alternative pathways - There
    is also significant diversity
  • Classification
  • Based on carbon requirement Autotrophs use CO2
    Heterotrophs use organic carbon
  • Based on energy source Phototrophs use light
    Chemotrophs use Glc, inorganic compounds NH4 S

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Living things exhibit metabolic diversity
  • Metabolic diversity among the 5 kingdoms
  • Oxygen is essential to life for aerobes
  • Aerobes
  • Anaerobes
  • Obligate aerobes, facultative anaerobes, and
    Obligate anaerobes

10
The Sun is Primary Energy for Life
  • The flow of energy in the biosphere and the
    carbon and oxygen cycles are intimately related
  • Phototrophs use light to drive synthesis of
    organic molecules
  • Heterotrophs use these organic molecules as
    building blocks
  • CO2, O2, and H2O are recycled

11
Figure 17.3The flow of energy in the biosphere
is coupled primarily to the carbon and oxygen
cycles.
12
17.2 How Do Anabolic and Catabolic Processes
Form the Core of Metabolism Pathways?
  • Metabolism serves two fundamentally different
    purposes the generation of energy to drive vital
    functions and synthesis of biological molecules
  • Metabolism consists of catabolism and anabolism
  • Catabolism degradative pathways
  • Usually energy-yielding
  • Oxidative
  • Anabolism biosynthetic pathways
  • Energy-requiring
  • Reductive

13
Figure 17.4Energy relationships between the
pathways of catabolism and anabolism. Oxidative,
exergonic pathways of catabolism release free
energy and reducing power that are captured in
the form of ATP and NADPH, respectively. Anabolic
processes are endergonic, consuming chemical
energy in the form of ATP and using NADPH as a
source of high energy electrons for reductive
purposes.
14
Anabolism and Catabolism Are Not Mutually
Exclusive
  • Catabolism and anabolism occur simultaneously in
    the cell
  • The conflicting demands of concomitant catabolism
    and anabolism are managed by cells in two ways
  • The cell maintains tight and separate regulation
    of both catabolism and anabolism
  • Competing metabolic pathways are often localized
    within different cellular compartment

15
Organization of Enzymes in Pathways
  • Pathways consist of sequential enzymatic steps
  • The enzymes may be
  • Separate, soluble entities
  • or may form a multienzyme complex
  • or may be a membrane-bound system
  • New research indicates that multienzyme complexes
    are more common than once thought - metabolons

16
Figure 17.5Schematic representation of types of
multienzyme systems carrying out a metabolic
pathway (a) Physically separate, soluble enzymes
with diffusing intermediates. (b) A multienzyme
complex. Substrate enters the complex and becomes
covalently bound and then sequentially modified
by enzymes E1 to E5 before product is released.
No intermediates are free to diffuse away. (c) A
membrane-bound multienzyme system.
17
The pathways of catabolism converge to a few end
products
  • Consists of three distinct stages
  • Stage 1 the nutrient macromolecules are broken
    down into their respective building blocks
  • Stage 2 building blocks are further degraded to
    yield an even more limit set of simpler metabolic
    intermediates
  • Stage 3 the oxidation of metabolic intermediates
    to generate the energy and to produce CO2 and H2O

18
Figure 17.6The three stages of catabolism. Stage
1 Proteins, polysaccharides, and lipids are
broken down into their component building blocks,
which are relatively few in number. Stage 2 The
various building blocks are degraded into the
common product, the acetyl groups of acetyl-CoA.
Stage 3 Catabolism converges to three principal
end products water, carbon dioxide, and ammonia.
19
Anabolic pathways diverge to synthesize many
biomolecules
  • The proteins, nucleic acids, lipids, and
    polysaccharides are constructed from appropriate
    building blocks via the pathways of anabolism
  • The building blocks (amino acid, nucleotides,
    sugars, and fatty acids) can be generated from
    metabolites
  • Some pathways serve both in catabolism and
    anabolism citric acid cycle- Such pathways are
    amphibolic

20
Comparing Pathways
  • Anabolic catabolic pathways involving the same
    product are not the same enzymatic reactions
  • Some steps may be common to both, others must be
    different - to ensure that each pathway is
    spontaneous
  • This also allows regulation mechanisms to turn
    one pathway on and the other off

21
Figure 17.7Parallel pathways of catabolism and
anabolism must differ in at least one metabolic
step in order that they can be regulated
independently. Shown here are two possible
arrangements of opposing catabolic and anabolic
sequenced between A and P. (a) The parallel
sequences proceed via independent routes. (b)
Only one reaction has two different enzymes, a
catabolic one (E3) and its anabolic counterpart
(E6). These provide sites for regulation.
22
ATP Serves in a Cellular Energy Cycle
  • ATP is the energy currency of cells
  • Phototrophs transform light energy into the
    chemical energy of ATP
  • In heterotrophs, catabolism produces ATP, which
    drives activities of cells
  • Energy released in the hydrolysis of ATP to ADP
    and Pi
  • ATP cycle carries energy from photosynthesis or
    catabolism to the energy-requiring processes of
    cells

23
Figure 17.8The ATP cycle in cells. ATP is formed
via photosynthesis in phototrophic cells or
catabolism in heterotrophic cells.
Energy-requiring cellular activities are powered
by ATP hydrolysis, liberating ADP and Pi.
24
NAD and NADH system in Metabolism
  • NAD collects electrons released from the
    substrates in oxidative reactions of catabolism
  • Catabolism is oxidative - substrates lose
    reducing equivalents, usually H- ions (hydride
    ion)
  • The hydride ions are transferred in enzymatic
    dehydrogenase reactions from the substrates to
    NAD molecules, reducing them to NADH
  • The ultimate oxidizing agent is O2, becoming
    reduced to H2O
  • Oxidation reaction s are exergonic, and the
    energy released is coupled with the formation of
    ATP

25
A comparison of state of reduction of carbon
atoms in biomolecules.
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27
NADPH provides the reducing power for anabolic
processes
  • Anabolism is reductive
  • The biosynthesis requires the reducing
    equivalents
  • NADPH provides the reducing power (electrons) for
    anabolic processes
  • In photosynthetic organism, the energy of light
    is used to pull electrons from water and transfer
    them to NAPD O2 is by-product of this process

28
Figure 17.11Transfer of reducing equivalents
from catabolism to anabolism via the NADPH cycle.
29
17.3 What Experiments Can Be Used to Elucidate
Metabolic Pathways?
  • Eduard Buchner (late 19th century) showed that
    fermentation of glucose in extract of broken
    yeast cells yielded ethanol and carbon dioxide.
  • This led to a search for intermediates of glucose
    breakdown.
  • Metabolic inhibitors were important tools for
    elucidating the pathway steps.
  • Mutations also were used to create specific
    metabolic blocks.

30
Figure 17.12The use of inhibitors to reveal the
sequence of reactions in a metabolic pathway. (a)
Control Under normal conditions, the
steady-state concentrations of a series of
intermediates will be determined by the relative
activities of the enzymes in the pathway. (b)
Plus inhibitor In the presence of an inhibitor
(in this case, an inhibitor of enzyme 4),
intermediates upstream of the metabolic block (B,
C, and D) accumulate, revealing themselves as
intermediates in the pathway. The concentration
of intermediates lying downstream (E and F) will
fall.
31
Isotopic Tracers Can Be Used as Metabolic Probes
  • Substrates labeled with an isotopic form of some
    element can be fed to cells and used to elucidate
    metabolic sequences
  • Radioactive isotopes 14C, 3H, 32P
  • Stable heavy isotopes 18O, 15N

CO2 H2O ? (CH2O) O2
C16O2 2 H218O ? (CH216O) H216O 18O2
32
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33
Figure 17.13One of the earliest experiments
using a radioactive isotope as a metabolic
tracer. Cells of Chlorella (a green alga)
synthesizing carbohydrate from carbon dioxide
were exposed briefly (5 sec) to 14C-labeled CO2.
The products of CO2 incorporation were then
quickly isolated from the cells, separated by
two-dimensional paper chromatography, and
observed via autoradiographic exposure of the
chromatogram. Such experiments identified
radioactive 3-phosphoglycerate (PGA) as the
primary product of CO2 fixation. The
3-phosphoglycerate was
labeled in the 1-position (in its carboxyl
group). Radioactive compounds arising from the
conversion of 3-phosphoglycerate to other
metabolic intermediates included
phosphoenolpyruvate (PEP), malic acid, triose
phosphate, alanine, and sugar phosphates and
diphosphates. (Photograph courtesy of Professor
Melvin Calvin, Lawmann Berkeley Laboratory,
University of California, Berkeley.)
34
Figure 17.14With NMR spectroscopy one can
observe the metabolism of a living subject in
real time. These NMR spectra show the changes in
ATP, creatine-P (phosphocreatine), and Pi levels
in the forearm muscle of a human subjected to 19
minutes of exercise. Note that the three P atoms
of ATP (a ,b, and g) have different chemical
shifts, reflecting their different chemical
environments.
35
Metabolic Pathways Are Compartmentalized Within
Cells
  • Eukaryotic cells are extensively
    compartmentalized by an endomembrane system
  • The flow of metabolic intermediates in the cell
    is spatially as well as chemically segregated

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Figure 17.16Compartmentalization of glycolysis,
the citric acid cycle, and oxidative
phosphorylation.
38
Figure 17.15Fractionation of a cell extract by
differential centrifugation. It is possible to
separate organelles and subcellular particles in
a centrifuge because their inherent size and
density differences give them different rates of
sedimentation in an applied centrifugal field.
Nuclei are pelleted in relatively weak
centrifugal fields, mitochondria in somewhat
stronger fields, whereas very strong centrifugal
fields are necessary to pellet ribosomes and
fragments of the endomembrane system.
39
17.4 What Food Substances Form the Basis of
Human Nutrition?
  • Protein is a rich source of nitrogen and also
    provides essential amino acids
  • Carbohydrates provide metabolic energy and
    essential components for nucleotides and nucleic
    acids
  • Lipids provide essential fatty acids that are key
    components of membranes and also important signal
    molecules
  • Fiber may be soluble or insoluble

40
Special Focus Vitamins
  • Many vitamins are "coenzymes" - molecules that
    bring unusual chemistry to the enzyme active site
  • Vitamins and coenzymes are classified as
    "water-soluble" and "fat-soluble"
  • The water-soluble coenzymes exhibit the most
    interesting chemistry

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42
Vitamin B1 Thiamine and Thiamine Pyrophosphate
  • Thiamine pyrophosphate (TPP)
  • Thiamine - a thiazole ring joined to a
    substituted pyrimidine by a methylene bridge
  • Thiamine-PP is the active form
  • TPP is involved in carbohydrate metabolism in
    which bonds to carbonyl carbons (aldehyde or
    ketone)
  • It catalyzes decarboxylations of a-keto acids and
    the formation and cleavage of a -hydroxyketones

43
Figure 17.17Thiamine pyrophosphate (TPP), the
active form of vitamin B1, is formed by the
action of TPP-synthetase.
Figure 17.18Thiamine pyrophosphate participates
in (a) the decarboxylation of a-keto acids and
(b) the formation and cleavage of
a-hydroxyketones.
44
Some Vitamins Contain Adenine Nucleotides
  • All use the adenine nucleotide group solely for
    binding to the enzyme
  • Several classes of coenzymes
  • pyridine dinucleotides
  • flavin mono- and dinucleotides
  • coenzyme A

45
Nicotinic Acid and the Nicotinamide Coenzymes
  • Two important coenzymes in this class
  • Nicotinamide adenine dinucleotide (NAD)
  • Nicotinamide adenine dinucleotide phosphate
    (NADP)
  • The reduced forms of these coenzymes are NADH and
    NADPH
  • The nicotinamide coenzymes are electron carriers
  • They transfer hydride anion (H-) to NAD(P) and
    from NAD(P)H

46
Figure 17.19The structures and redox states of
the nicotinamide coenzymes. Hydride ion (H-, a
proton with two electrons) transfers to NAD to
produce NADH.
47
Figure 17.20NAD and NADP participate
exclusively in two-electron transfer reactions.
For example, alcohols can be oxidized to ketones
or aldehydes via hydride transfer to NAD(P).
48
Nicotinamide Coenzymes
  • Structural and mechanistic features
  • The quaternary nitrogen of the nicotinamide ring
    acts as an electron sink to facilitate hydride
    transfer
  • The C4-position (on the nicotinamide ring) of
    hydride transfer is a pro-chiral center
  • Hydride transfer is always stereospecific -
    pro-R, pro-S position

49
Niacin and Pellagra
  • Nicotinamide was first isolated in 1937 by
    Elvehjem at the University of Wisconsin
  • Note similarities between structures of pyridine,
    nicotinic acid, nicotinamide and nicotine
  • Tryptophan

50
Riboflavin and the Flavin Coenzymes
  • Riboflavin, or Vitamin B2
  • Active forms are flavin mononucleotide (FMN) and
    flavin adenine dinucleotide (FAD)
  • All these substances contain ribitol and a flavin
    or isoalloxazine ring
  • FMN is not a true nucleotide
  • FAD is not a dinucleotide
  • But the names are traditional and they persist

51
Figure 17.21The structures of riboflavin, flavin
mononucleotide (FMN), and flavin adenine
dinucleotide (FAD). Flavin coenzymes bind tightly
to the enzymes that use them, with typical
dissociation constants in the range of 10-8 to
10-11 M, so that only very low levels of free
flavin coenzymes occur in most cells. Even in
organisms that rely on the nicotinamide coenzymes
(NADH and NADPH) for many of their
oxidation-reduction cycles, the flavin coenzymes
fill essential roles. Flavins are stronger
oxidizing agents than NAD and NADP. They can be
reduced by
both one-electron and two-electron pathways and
can be reoxidized easily by molecular oxygen.
Enzymes that use flavins to carry out their
reactions flavoenzymes are involved in many
kinds of oxidation-reduction reactions.
52
Flavin Mechanisms
  • Flavins are one- or two-electron transfer agents
  • Name "flavin" comes from Latin flavus for
    "yellow"
  • The oxidized form is yellow, semiquinones are
    blue or red and the reduced form is colorless
  • Flavin coenzymes participate in one-electron
    transfer and two-electron transfer reactions

53
Figure 17.22The redox states of FAD and FMN. The
boxes correspond to the colors of each of these
forms. The atoms primarily involved in electron
transfer are indicated by red shading in the
oxidized form, white in the semiquinone form, and
blue in the reduced form.
Higher pH
Physiological pH
54
Pantothenic Acid and Coenzyme A
  • Pantothenic acid (vitamin B3) is a component of
    Coenzyme A (fig. 17.23)
  • Functions
  • Activation of acyl groups for transfer by
    nucleophilic attack
  • Activation of the a-hydrogen of the acyl group
    for abstraction as a proton
  • Both of these functions are mediated by the
    reactive -SH group on CoA, which forms thioester
    linkages with acyl groups

55
Figure 17.23The structure of coenzyme A. Acyl
groups form thioester linkages with the SH group
of the ß-mercaptoethylamine moiety.
56
  • Acetyl-CoA has a high group-transfer potential
  • Ethyl acetate H2O ? acetate ethanol H
    DGo - 20KJ/mol
  • Acetyl-CoA H2O ? acetate CoA-SH H DGo
    - 31KJ/mol
  • Transfer of the acetyl-group from acetyl-CoA is
    more spontaneous than from an oxygen ester
  • The 4-phosphopantetheine group is also in acyl
    carrier protein in fatty acid biosynthesis

Figure 17.24Acyl transfer from acyl-CoA to a
nucleophile is more favorable than transfer of an
acyl group from an oxygen ester.
57
Vitamin B6 Pyridoxine and Pyridoxal Phosphate
  • Pyridoxine and pyridoxal-5-phosphate (PLP)
  • Exists in two tautomeric forms (Fig. 17.25)
  • Catalyzes reactions involving amino acids
    Transaminations, decarboxylations, eliminations,
    racemizations and aldol reactions (Fig. 17.26)
  • This versatile chemistry is due to
  • formation of stable Schiff base (aldimine)
    adducts with a-amino groups of amino acids
  • Act as effective electron sink to stabilize
    reaction intermediates

58
Figure 17.25

(aldimine) The
tautomeric forms of pyridoxal-5-phosphate (PLP).

59
Figure 17.26The seven classes of reactions
catalyzed by pyridoxal-5-phosphate. 1.
Transamination 2. a-decarboxylation 3.
b-decarboxylation 4. b-elimination 5.
g-elimination 6. Racemization 7. Aldol reactions
60
Pyridoxal Phosphate
  • Mechanisms
  • Figure 17.27 is a key figure - relate each
    intermediate to subsequent mechanisms
  • A Schiff base linkage with the e-NH2 group of an
    active site lysine in the absence of substrate
  • Appreciate the fundamental difference between
    intermediates 2 through 7

61
Figure 17.27Pyriodoxal-5-phosphate forms stable
Schiff base adducts with amino acids and acts as
an effective electron sink to stabilize a variety
of reaction intermediates.
62
Vitamin B12 Contains the Metal Cobalt
  • Cyanocobalamin
  • B12 is converted into two coenzymes in the body
  • 5'-deoxyadenosylcobalamin
  • methylcobalamin

63
Figure 17.28 The structure of cyanocobalamin
(top) and simplified structures showing several
coenzyme forms of vitamin B12. The CoC bond of
5'deoxyadenosylcobalamin is predominantly
covalent (note the short bond length of 0.205 nm)
but with some ionic character. Note that the
convention of writing the cobalt atom as Co3
attributes the electrons of the CoC and CoN
bonds to carbon and nitrogen, respectively.
64
B12 Function Mechanism
  • B12 catalyzes 3 kinds of reactions
  • Intramolecular rearrangements (isomerization
    mutase)
  • Reductions of ribonucleotides to
    deoxyribonucleotides (in certain bacteria)
  • Methyl group transfers (assisted by
    tetrahydrofolate - which is covered in a later
    section of this chapter)

65
Figure 17.29Vitamin B12 functions as a coenzyme
in intramolecular rearrangements, reduction of
ribonucleotides, and methyl group transfers.
66
Vitamin C Ascorbic Acid
  • Ascorbic acid
  • Most plants and animals make ascorbic acid - for
    them it is not a vitamin
  • Only a few vertebrates - man, primates, guinea
    pigs, fruit-eating bats and some fish (rainbow
    trout, carp and Coho salmon) cannot make it
  • Vitamin C is a reasonably strong reducing agent
  • It functions as an electron carrier

67
Figure 17.30The physiological effects of
ascorbic acid (vitamin C) are the result of its
action as a reducing agent. A two-electron
oxidation of ascorbic acid yields dehydroascorbic
acid.
68
Roles of Vitamin C
  • Many functions in the body
  • Hydroxylations of proline and lysine (essential
    for collagen) are Vitamin C-dependent
  • Metabolism of Tyr in brain depends on C
  • Fe mobilization from spleen depends on C
  • C may prevent anemia
  • C ameliorates allergic responses
  • C can stimulate the immune system

69
Biotin
  • "chemistry on a tether"
  • Biotin functions as a mobile carboxyl group
    carrier in a variety of enzymatic carboxylation
    reactions
  • Bound covalently to a lysine residue on the
    protein
  • The biotin-lysine conjugate is called biocytin
  • The biotin ring system is thus tethered to the
    protein by a long, flexible chain

70
Figure 17.31The structure of biotin
Figure 17.32Biotin is covalently linked to a
protein via the e-amino group of a lysine
residue. The biotin ring is thus tethered to the
protein by a ten-atom chain. It functions by
carrying carboxyl groups between distant sites on
biotin-dependent enzymes.
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72
Biotin Carboxylations
  • Most use bicarbonate and ATP
  • Whenever you see a carboxylation that requires
    ATP and CO2 or HCO3-,
  • Activation by ATP involves formation of carboxyl
    phosphate
  • Carboxyl group is transferred to biotin to form
    N-carboxy-biotin
  • The "tether" allows the carboxyl group to be
    shuttled from the carboxylase subunit to the
    transcarboxylase subunit of ACC-carboxylase

73
Lipoic Acid
  • Another example of "chemistry on a tether"!
  • Lipoic acid, like biotin, is a ring on a chain
    and is linked to a lysine on its protein
  • Lipoic acid is an acyl group carrier
  • Found in pyruvate dehydrogenase and
    ?-ketoglutarate dehydrogenase
  • Lipoic acid functions to couple acyl-group
    transfer and electron transfer during oxidation
    and decarboxylation of ?-keto acids

74
Figure 17.33The oxidized and reduced forms of
lipoic acid and the structure of the lipoic
acid-lysine conjugate.
Figure 17.34The enzyme reactions catalyzed by
lipoic acid.
75
Folic Acid
  • Folates are donors of 1-C units for all oxidation
    levels of carbon except that of CO2
  • Active form is tetrahydrofolate (THF)
  • THF is formed by two successive reductions of
    folate by dihydrofolate reductase
  • The oxidation states in Table 17.6

76
page 571
77
Figure 17.35Formation of THF from folic acid by
the dihydrofolate reductase reaction. The R group
on these folate molecules includes the one to
seven (or more) glutamate units that folates
characteristically contain. All of these
glutamates are bound in g-carboxyl amide linkages
(as in the folic acid structure shown in the A
Deeper Look box on page 571). The one-carbon
units carried by THF are bound at N5, or at N10,
or as a single carbon attached to both N5 and N10.
(DHF)
(THF)
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79
Vitamin A Group Includes Retinol, Retinal, and
Retinoic Acid
  • Retinol, retinyl esters and retinal
  • Retinol is absorbed from animal source and
    synthesized from b-carotene from plant source
  • Retinol is esterified and transported to the
    liver
  • Retinol is converted to retinal in the retina of
    the eye and is linked to opsin to form rhodopsin,
    a light-sensitive pigment protein in the rods and
    cones (fig 17.36)
  • Retinoic acid affects growth, differentiation,
    and development

80
Figure 17.36The incorporation of retinal into
the light-sensitive protein rhodopsin involves
several steps. All-trans-retinol is oxidized by
retinol dehydrogenase and then isomerized to
11-cis-retinal, which forms a Schiff base linkage
with opsin to form light-sensitive rhodopsin.
81
Vitamin D Is Essential for Proper Calcium
Metabolism
  • Ergocalciferol and cholecalciferol
  • Cholecalciferol is made in the skin by the action
    of UV light on 7-dehydrocholesterol
  • Major circulating form is 25-hydroxyvitamin D
  • 1,25-dihydroxycholecalciferol (1,25-dihydroxyvitam
    in D3) is the most active form
  • It functions to regulate calcium homeostasis
  • and plays a role in phosphorus homeostasis

82
Figure 17.37(a) Vitamin D3 (cholecalciferol) is
produced in the skin by the action of sunlight on
7-dehydrocholesterol. The successive action of
mixed-function oxidases in the liver and kidney
produces 1,25-dihydroxyvitamin D3, the active
form of vitamin D. (b) Ergocalciferol is produced
in analogous fashion from ergosterol.
Circuratory system
83
Vitamins E and K
  • Less understood vitamins
  • Vitamin E (?-tocopherol) is a potent antioxidant
  • Molecular details are almost entirely unknown
  • May prevent membrane oxidations (unsaturated
    fatty acids)
  • Vitamin K is essential for blood clotting
  • A post-translational modification of prothrombin
    is essential to its function
  • Carboxylation of 10 glutamyl residues on
    prothrombin (to form ?-carboxyglutamyl residues)
    is catalyzed by a vitamin K-dependent enzyme,
    liver microsomal glutamyl carboxylase

84
Figure 17.38 The structure of vitamin E
(a-tocopherol).
Figure 17.39The structures of the K vitamins.
85
Figure 17.40The glutamyl carboxylase reaction is
vitamin K-dependent. This enzyme activity is
essential for the formation of g-carboxyglutamyl
residues in a variety of proteins, including
several proteins of the blood-clotting cascade
(Figure 15.4). These latter carboxylations
account for the vitamin K dependence of
coagulation.
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