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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5626_Библиотеки_им_академика_М_И_Перельмана.pdf
1. Definition of Xymozymes: A term used interchange-
2. Definition of Coenzymes: Small organic molecules,
Example: NAD+ and FAD are coenzymes involved in
3. Definition of Cofactors: Inorganic ions or molecules
13.5 Role of Enzymes in Biosynthetic Pathways 261
5. Substrate Channeling: Enzymes facilitate substrate
6. Isolation of Intermediates: Enzymes assist in the
Example: Metal ions such as Mg2+ or Zn2+ can act as
13.4.2 Catalytic Mechanism
1. Catalysis: Enzymes accelerate chemical reactions in
7. Energy Efficiency: Enzymes contribute to the energy
8. Synthesis of Biomolecules: Enzymes are directly
13.5 Role of Enzymes in Biosynthetic Pathways
2. Specificity: Enzymes exhibit high specificity for par-
3. Regulation: Enzymes provide a means of regulation
4. Control Points: Certain enzymes in biosynthetic
13.5.1 Basic Metabolic Pathway and Their Utilization to Produce Secondary Metabolite
13.5.1.1 Basic Metabolic Pathways
1. Glycolysis: Source of precursor: glucose. Utilization
3. Regulation of Enzymes: Enzymes involved in pri-
4. Cellular Compartmentalization: Certain secondary
5. Environmental Factors: External variables that
2. Citric Acid Cycle (Krebs cycle): Source of precur-
3. Pentose Phosphate Pathway: Source of precursor:
4. Amino Acid Biosynthesis: Source of precursor:
13.5.1.2 Utilization for Secondary Metabolites
1. Precursor Availability: Secondary metabolites often
2. Branching Points: Intermediates at the branching
13.5.1.3 Intermediates and Possible Diversion
of Pathways
1. Acetyl-CoA:
Key Intermediate: acetyl-CoA is a central intermedi-
Diversion: it serves as a precursor for the biosynthesis
2. Malonyl-CoA:
Key Intermediate: malonyl-CoA is produced from
Diversion: It is utilized in the polyketide pathway for
3. Mevalonate:
Key Intermediate: mevalonate is an intermediate
Diversion: mevalonate serves as a precursor for the
4. Phenylalanine and Tyrosine:
Key Intermediates: phenylalanine and tyrosine are
Diversion: these amino acids are precursors for the
5. Chorismate:
Key Intermediate: chorismate is an intermediate in
13.6 Other Structural Modifications 263
Diversion: chorismate is a branching point for the
6. Isopentenyl Diphosphate and Dimethylallyl
Diphosphate:
Key Intermediates: isopentenyl diphosphate (IPP)
Diversion: these isoprenoid precursors are used for
7. S-Adenosyl Methionine:
Key Intermediate: s-adenosyl methionine (SAM) is
Diversion: SAM is involved in the methylation of sec-
8. UDP-Glucose:
Key Intermediate: UDP-Glucose is a sugar nucleo-
Diversion: It serves as a substrate for glycosylation
13.6 Other Structural Modifications
13.6.1 Isomerization
13.6.2 Hydrogenation and Dehydrogenation
13.6.3 Ring-Opening and Ring-closing Reactions
13.5.1.4 Keto-enol Tautomerism
13.6.4 Functional Group Inter-conversion
13.6.5 Modern Techniques in Structural Elucidation
13.6.6 Importance in Drug Design and Synthesis
3. Mevalonate:
Role in Secondary Metabolism: mevalonate is a pre-
4. Chorismate:
Role in Secondary Metabolism: chorismate is a piv-
5. S-Adenosyl Methionine:
Role in Secondary Metabolism: SAM is involved in
6. UDP-Glucose:
Role in Secondary Metabolism: UDP-glucose is a
13.6.7 Intermediates and End Products in Secondary Metabolic Pathways
1. Acetyl-CoA:
Role in Secondary Metabolism: acetyl-CoA is a cen-
2. Malonyl-CoA:
Role in Secondary Metabolism: malonyl-CoA,
13.6.8 Integration of Pathways
Polyketide-Terpenoid Hybrid Pathways: A few organ-
Compounds Derived from Amino Acids: Nitrogen
Regulation by the Environment and Development:
13.7 Shikimic Acid Pathway for
Biosynthesis of Aromatic
Amino Acids
13.7 Shikimic Acid Pathway for Biosynthesis of Aromatic Amino Acids 265
1. As per Figure 13.2, nicotinamide adenine dinucleotide
2. The next step is the conversion of 2-keto-3-deoxy-
3. The reaction between phosphoenolpyruvate and
4. 5-Enolpyruvylshikimate-3-phosphate is then con-
5. 5-Shikimate-3-phosphate and phosphoenol pyruvate
6. The enzyme 3-dehydroquinate dehydratase dehydrates
7. Next, chorismate is rearranged by Chorismate mutase
8. Biosynthesis of gallic acid through the activity of the
Phosphenolpyruvate
heptulosonate-7-phosphate
Erythrose4-phosphate
3-Deoxy-D-arabino-heptulosonate-
7-phosphate synthase (DAHPS)
3-Deoxy-D-arabino-
3-Dehydroquinate
synthase (DHQS)
3-Dehydroquinate
3-Dehydroquinate
dehydratase (DHQ)
3-Dehydroshikimate
Shikimate -5-dehydrogenase
Shikimate
Shikimate kinase (SK)
Shikimate 3-
phosphate
5-Endopyruvylshikimate 3-
phosphate synthase (EPSPS)
5-Endopyruvylshikimate
3-phosphate
Chorismate synthase (CS)
Chorismate
Glyphosate
Aromatic amino acids
Figure 13.1 Shikimic acid pathway. Source: Balkrishna Tiwari, D.N. Tiwari, in Cyanobacteria, 2019, https://www.sciencedirect.com/
topics/neuroscience/3-phosphoshikimate-1-carboxyvinyltransferase
13.8 Acetate Mevalonate Pathway
for Biosynthesis of Terpenes
13.8 Acetate Mevalonate Pathway for Biosynthesis of Terpenes 267
O
O
Phosphoenolpyruvate
H
OPO
3
–
D-Erythro-4-phosphate
3-Deaxy-
phosphate synthase (DAHPS)
HO3PO
3-Deaxy-D-arabino-heptulsonic acid-7-phosphate
OH
OH
OH
O
COOH
3-Dehydroquinate synthase
COOH
HO
O
OH
OH
3-Dehydroquinic acid
3-Dehydroquinate dehydratase (DHQ/SDH)
COOH
HO
Gallic acid (3,4,5-THBA)
OH
OH
COOH
OH
Protocatechuic acid
COOH
HO
Shikimate-5-dehydrogenase
HO
OH
OH
OH
3-Dehydroquinic acid
COOH
HO
OH
Shikimate-3-phosphate
5-Enolpyruvylshikimate-3-phosphate synthase (EPSPS)
COOH
HO
O
O
5-Enolpyruvylshikimic acid-3-phosphate
Chorismate synthase (CS)
OPO
OH
H
3
HO
O
D-arabino-heptulsonate-7-
HO
HO
OH
COOH
OH
OPO3H
OH
Quinic acid
HO
Shikimate kinase (SK)
OPO3H
HO
COOH
NH
2
anthranilic acid
COOH
OH
OH
Shikimic acid
O
O
Chorismic acid
MeO
COOH
OH
Folates
HO
OMe
Syringic acid
MeO
HO
Vanillic acid
HO
HO
3,4-DHBA
HO
p-HBA
Benzoic acid
Salicylic acid
O
p-NH
2
COOH
COOH
COOH
COOH
COOH
COOH
OH
HO
+
H
N
3
–
OC
L-Arogenate
COOH
NH
2
-benzoic acid
MeO
HO
OCH
Sinapic acid
3
MeO
HO
Feruic acid
HO
HO
Caffeic acid
HO
p-Coumaric acid
trans-Cinnamic acid
PA L
COOH
Phenylalanine
Gentisic acid
COOH
Phenylpyruvic acid
OH
COOH
O
HOOC
Pr
HO
p-Hydroxyphenylpyruvic acid
O
O
OH
O
OH
O
OH
O
OH
O
OH
O
OH
NH
2
O
OH
O
OH
ephenic acid
O
OH
Figure 13.2 Biosynthesis of aromatic amino acid by shikimic acid pathway. Source: Guy B. Kougan, Robert Verpoorte, in Medicinal Plant
Research in Africa, 2013, https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/shikimic-acid-pathway
1. Biochemists have long been aware of acetic acid’s role
4. Thus, the acetate mevalonate pathway produces two
2. IPP and its isomer, DMAPP, were also generated by
3. Geranyl-eranyl pyrophosphate (C20-diterpenes) is pro-
O
HO
Mevalonate-
5-diphosphate
ERG19
DMAPP
Glucose
OH
IPP
IDII
OPP
AT P
ADP + P
OPP
OPP
ERG10
O
CoA
acetyl-CoA acetoacetyl-CoA
ERG8
ADP
+ CO
i
ERG20
HO
AT P
2
O
O
OH
Mevalonate5-phosphate
GPP
O
OP
ERG20
CoA
ADP
OPP
ERG13
2 NADPH
ERG12
AT P
HO
2 NADP
HO
O
OH
HMG-CoA
HMG1
+
O
OH
Mevalonate
O
CoA
OH
FPP
Terpenes
OPP
Figure 13.3 Isoprenoid biosynthesis. Source: Joseph A Chemler, Yajun Yan & Mattheos AG Koffas. Microbial Cell Factories volume 5,
Article number: 20 (2006), https://microbialcellfactories.biomedcentral.com/articles/10.1186/1475-2859-5-20#Fig1
13.9 Biosynthesis of Aliphatic
Amino Acids
1. In living things, the production of aliphatic amino
2. Alanine biosynthesis: Alanine is synthesized from
3. Valine, leucine, and isoleucine biosynthesis: Valine,
13.10 Acetate Mevalonate Pathways for Biosynthesis of Fatty Acyl-CoA 269
13.10 Acetate Mevalonate Pathways for Biosynthesis of Fatty Acyl-CoA
From: Glucose
Pentose phosphate
pathway
Glycolysis
Citric acid cycle (CAC)
HO
(E4P)(E4P)
O
OH
O
P
HO
HO
Erythrose 4-Erythrose 4-
O
phosphatephosphate
Phenylalanine (Phe, F)
Tyrosine (Tyr, Y)
Tryptophan (Tyr, W)
O
HO
OH
O
O
Oxaloacetate
Aspartate (Asp, D)
Asparagine (Asn, N)
Methionine (Met, M)
Threonine (Thr, T)
Lysine (Lys, K)
Glucose-6-phospate (G6P)
4 steps
HO
O
P
HO
O
3-Phosphoglycerate (3PG)3-Phosphoglycerate (3PG)
HO
O
P
HO
O
Phosphoenolpyruvate (PEP)Phosphoenolpyruvate (PEP)
O
OH
PyruvatePyruvate
O
Citrate
Citric acid cycle
(CAC)
4 steps
OH
O
Ribose 5-phosphate (R5P)Ribose 5-phosphate (R5P)
OH
O
OH
O
OH
Histidine (His, H)
Serine (Ser, S)
Alanine (Ala, A)
Valine (Val, V)
Isoleucine (Ile, I)
Leucine (Leu, L)
O
HO
α-Ketoglutarate
O
Glutamate (Glu, E)
Glutamine (Gln, Q)
Proline (Pro, P)
Arginine (Arg, R)
OH
OH
OH
O
P
OH
O
O
OH
Figure 13.4 Amino acid pathway. Source: https://microbialcellfactories.biomedcentral.com/articles/10.1186/1475-2859-5-20#Fig1
1. Acetyl-CoA generation
2. Malonyl-CoA formation
3. Initiation of fatty acid synthesis
4. Fatty Acid Elongation
5. Formation of Palmitic Acid
6. Desaturation and Chain Elongation (Optional)
7. Incorporation of Isoprenoid Intermediates
2 Acetyl-CoA
Acetoacetyl-CoA Thiolase
E.C. 2.3.1.9
Acetoacetyl-CoA
HMG-CoA Synthase
E.C. 4.1.3.5
HMG-CoA
HMG-CoA Reductase
E.C. 1.1.1.34
Mevalonate
Mevalonate Kinase
E.C. 2.7.1.36
Mevalonate-5-phosphate
Phosphomevalonate Kinase
E.C. 2.7.4.2
Mevalonate-5-pyrophosphate
Diphosphomevalonate
Decarboxylase
E.C. 4.1.1.33
Isopentenyl diphosphate
O
SCoA
O
O
SCoA
O
HO
–
O
O
–
O
O
–
O
O
–
O
HO
HO
HO
CH
CH
2
3
CH
CH
CH
O
SCoA
3
OH
3
OP
3
OPOP
OPOP
Figure 13.5 Mevalonic acid pathway. Source: Similar image created by corresponding Author P. N. Chougule by using reference
https://2019.igem.org/Team:XJTU-CHINA/Model