Transcript CHAPTER 6

Chapter 17
Metabolism – An Overview
Biochemistry
by
Reginald Garrett and Charles Grisham
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
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
1 or 2
3
4
5
6 or
more
Dots
410
71
20
11
8
Outline of Chapter 17
1. Are There Similarities of Metabolism
Between Organisms?
2. How Do Anabolic and Catabolic Processes
Form the Core of Metabolic Pathways?
3. What Experiments Can Be Used to Elucidate
Metabolic Pathways?
4. What Food Substances Form the Basis of
Human Nutrition?
Special Focus: Vitamins
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
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
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
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
Figure 17.3
The flow of energy in the biosphere is coupled primarily to the carbon and oxygen cycles.
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
Figure 17.4
Energy 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.
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
1. The cell maintains tight and separate regulation
of both catabolism and anabolism
2. Competing metabolic pathways are often
localized within different cellular compartment
Organization of Enzymes in Pathways
•
•
Pathways consist of sequential enzymatic steps
The enzymes may be
1. Separate, soluble entities
2. or may form a multienzyme complex
3. or may be a membrane-bound system
•
New research indicates that multienzyme
complexes are more common than once thought
- metabolons
Figure 17.5
Schematic
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.
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
Figure 17.6
The 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.
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
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
Figure 17.7
Parallel 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 it’s anabolic counterpart (E6). These provide sites for regulation.
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 energyrequiring processes of cells
Figure 17.8
The 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.
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
Figure 17.9
Comparison of the state of reduction of carbon atoms in biomolecules: -CH2- (fats) > CHOH- (carbohydrates) C=O (carbonyls) > -COOH (carboxyls) >CO2 (carbon dioxide,
the final products of catabolism).
A comparison of state of reduction of
carbon atoms in biomolecules.
Figure 17.10
Hydrogen and electrons released in the course of oxidative catabolism are transferred as
hydride ions to the pyridine nucleotide, NAD+, to form NADH + H+ in dehydrogenase
reactions of the type
AH2 + NAD+ → A + NADH + H+
The reaction shown is catalyzed by alcohol dehydrogenase.
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 byproduct of this process
Figure 17.11
Transfer of reducing
equivalents from
catabolism to
anabolism via the
NADPH cycle.
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.
Figure 17.12
The 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.
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 +
18O
2
Figure 17.13
One 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 CO . The
2
products of CO2
incorporation were then
quickly isolated from the
cells, separated by twodimensional paper
chromatography, and
observed via
autoradiographic exposure of
the chromatogram. Such
experiments identified
radioactive 3phosphoglycerate (PGA) as
the primary product of CO2
fixation. The 3phosphoglycerate was
labeled in the 1-position (in its carboxyl group). Radioactive
compounds arising from the conversion of 3phosphoglycerate 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.)
Figure 17.14
With 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.
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
Figure 17.16
Compartmentalization of glycolysis, the citric acid cycle, and oxidative phosphorylation.
Figure 17.15
Fractionation 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.
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
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
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
Figure 17.17
Thiamine pyrophosphate (TPP), the active form of vitamin B1, is formed by the
action of TPP-synthetase.
Figure 17.18
Thiamine pyrophosphate participates in (a) the decarboxylation of a-keto acids and (b)
the formation and cleavage of a-hydroxyketones.
Some Vitamins Contain Adenine Nucleotides
•
All use the adenine nucleotide group
solely for binding to the enzyme
• Several classes of coenzymes:
1. pyridine dinucleotides
2. flavin mono- and dinucleotides
3. coenzyme A
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
Figure 17.19
The structures and redox states of the nicotinamide coenzymes. Hydride ion
(H:-, a proton with two electrons) transfers to NAD+ to produce NADH.
Figure 17.20
NAD+ 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)+.
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
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
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
Figure 17.21
The 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 oxidationreduction 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.
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
Figure 17.22
The 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.
Physiological pH
Higher pH
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
Figure 17.23
The structure of coenzyme A. Acyl groups
form thioester linkages with the —SH
group of the β-mercaptoethylamine
moiety.
• 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 17.24
Acyl transfer from acyl-CoA to a nucleophile is more favorable than
transfer of an acyl group from an oxygen ester.
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:
1. formation of stable Schiff base (aldimine) adducts
with a-amino groups of amino acids
2. Act as effective electron sink to stabilize reaction
intermediates
Figure 17.25
The tautomeric forms of pyridoxal-5-phosphate (PLP).
(aldimine)
Figure 17.26
The seven classes of reactions
catalyzed by pyridoxal-5phosphate.
1. Transamination
2. a-decarboxylation
3. b-decarboxylation
4. b-elimination
5. g-elimination
6. Racemization
7. Aldol reactions
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
Figure 17.27
Pyriodoxal-5-phosphate
forms stable Schiff base
adducts with amino
acids and acts as an
effective electron sink to
stabilize a variety of
reaction intermediates.
Vitamin B12 Contains the Metal Cobalt
Cyanocobalamin
• B12 is converted into two coenzymes in the
body:
– 5'-deoxyadenosylcobalamin
– methylcobalamin
Figure 17.28 The structure of cyanocobalamin (top) and simplified structures showing several
coenzyme forms of vitamin B12. The Co—C 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 Co—C and Co—N bonds to carbon and nitrogen, respectively.
B12 Function & Mechanism
•
B12 catalyzes 3 kinds of reactions:
1. Intramolecular rearrangements
(isomerization; mutase)
2. Reductions of ribonucleotides to
deoxyribonucleotides (in certain bacteria)
3. Methyl group transfers (assisted by
tetrahydrofolate - which is covered in a later
section of this chapter)
Figure 17.29
Vitamin B12 functions as a
coenzyme in intramolecular
rearrangements, reduction
of ribonucleotides, and
methyl group transfers.
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
Figure 17.30
The physiological effects of ascorbic
acid (vitamin C) are the result of its
action as a reducing agent. A twoelectron oxidation of ascorbic acid
yields dehydroascorbic acid.
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
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
Figure 17.31
The structure of biotin
Figure 17.32
Biotin is covalently linked to a
protein via the ε-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 biotindependent enzymes.
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
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 aketoglutarate dehydrogenase
• Lipoic acid functions to couple acyl-group
transfer and electron transfer during oxidation
and decarboxylation of a-keto acids
Figure 17.33
The oxidized and reduced forms of lipoic acid and the structure of the lipoic acid-lysine
conjugate.
Figure 17.34
The enzyme reactions catalyzed by lipoic acid.
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
page 571
Figure 17.35
Formation 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)
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
Figure 17.36
The 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.
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 (1,25dihydroxyvitamin D3) is the most active form
• It functions to regulate calcium homeostasis
• and plays a role in phosphorus homeostasis
Figure 17.37
(a) Vitamin D3
(cholecalciferol) is
produced in the skin by
the action of sunlight on 7dehydrocholesterol. The
successive action of
mixed-function oxidases in
the liver and kidney
produces 1,25dihydroxyvitamin D3, the
active form of vitamin D.
(b) Ergocalciferol is
produced in analogous
fashion from ergosterol.
Circuratory
system
Vitamins E and K
Less understood vitamins
• Vitamin E (a-tocopherol) is a potent antioxidant
1. Molecular details are almost entirely unknown
2. 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 g-carboxyglutamyl residues) is
catalyzed by a vitamin K-dependent enzyme, liver
microsomal glutamyl carboxylase
Figure 17.38 The structure of vitamin E (αtocopherol).
Figure 17.39
The structures of the K vitamins.
Figure 17.40
The glutamyl carboxylase
reaction is vitamin K-dependent.
This enzyme activity is essential
for the formation of gcarboxyglutamyl residues in a
variety of proteins, including
several proteins of the bloodclotting cascade (Figure 15.4).
These latter carboxylations
account for the vitamin K
dependence of coagulation.