“Gomel State Medial University”
Board of Biologic Chemistry
Formulas, reactions, metabolic pathways and schemes
in biologic chemistry
Enzymology and biologic oxidation
Manual for students
Gomel, 2014
2
1. Enzymology and biologic oxidation Introduction
Amino acids (AA) formulas
Essential amino acids
H2N CH COOH
CH2
Phenylalanine
H2N CH COOH
CH2
CH2
S
CH3
Methionine Threonine Tryptophan
H2N CH COOH
CH OH
CH3
H2N CH COOH
CH2
HN
H2N CH COOH
CH CH3
CH3
H2N CH COOH
CH2
CH2
CH2
CH2
NH2
H2N CH COOH
CH2
CH CH3
CH3
H2N CH COOH
CH CH3
CH2
CH3
Valine
Lysine
Leucine Isoleucine
Branched chain amino acids, BCAA
Условно заменимые
Non-essential amino acids
H2N CH COOH
CH3
H2N CH COOH
H
HN
COOH H2N CH COOH
CH2
OH
H2N CH COOH
CH2
C
NH2
O
H2N CH COOH
CH2
C
OH
O
H2N CH COOH
CH2
CH2
C
OH
O
H2N CH COOH
CH2
CH2
C
NH2
O
Glycine Alanine ProlineSerine
AsparagineAspartic acid Glutamic acid Glutamine
Partially essential amino acids
H2N CH COOH
CH2
CH2
CH2
NH
C
NH2
NH
H2N CH COOH
CH2
N
NH
Arginine Histidine
H2N CH COOH
CH2
SH
H2N CH COOH
CH2
OH
Tyrosine Cysteine
3
Enzymes-1
Determination of peptide charges, and pKa values of amino acids
Table 1
In the charge formation the radical of the following amino acids are involved: a. positively charged (arginine (Arg), histidine (His), lysine (Lys)) b. negatively charged (aspartic (Asp) and glutamic (Glu)) c. uncharged polar (cysteine (Cys) and tyrosine (Tyr)). d. terminal α-amino (α-NH3 +) and carboxyl (α-COO-) groups in oligopeptides.
The corresponding pKa values are taken into account for these amino acids (Table. 1). pKa values serves as critical points of the function, since there is a change of charge occurs in the corresponding pH.
Approximate pKa values for amino acids side chains and structures, which can be
chargeable: positive negative
His 6,5 α-COO- 2,5
Asp 3,9
α-NH3+ 9,0 Glu 4,1
Lys 10,5 Cys 8,2
Arg 12,5 Tyr 10,1
4
Enzymes-2
Vitamins B1, B2, B3, PP, B6, and coenzymes
COOH
N
COOHCH2CH2NHCCHCCH2HO
CH3
CH3 OH O
CH2OH
CH2OH
NH3C
HO
Riboflavin (B2)Thiamin (B1)
Vitamin PP (B5) Pyridoxine, vitamin B6
Pantothenic acid (B3)
OH
NH2
CH2
N+
S
CH2 CH2
CH3
N
H3C N
CONH2
N
Nicotinic acid Nicotinamide
NH
N
O
ON
NH3C
H3C
CH2CHCHCHHOH2C
OHOHOH
H2C
CH2OH
NH3C
HO
NH2C
CH2OH
NH3C
HO
OH
Pyridoxol Pyridoxal Pyridoxamine
O
O
CH3O
O
H3C
H3C
CH3
H
Coenzyme Q (CoQ, ubiquinone)
O
NH2
CH2N+
S
CH2 CH2
CH3
N
H3C N
Thiamin pyrophosphate (TPP)Thiamin diphosphate (TDP)
P
O
OH
O P
O
OH
OH
6-10
C
CH2
NH3C
HO
O
P
O
O OH
OH
H
Pyridoxal phosphate (PLP)
N
NN
N
NH2
O
OHOH
HH
CH2
H
P O
OH
O
O
P
OH
O
OP
OH
O
HO
N
NN
N
NH2
O
OHOH
HH
CH2
H
P O
OH
O
O
P
OH
O
HO
N
NN
N
NH2
O
OHOH
HH
CH2
H
P O
OH
HO
O
N
NN
N
NH2
O
OHO
HH
CH2
H
O
PO
OHAdenosine tpiphosphate (ATP) Adenosine diphosphate (ADP) Adenosine monohosphate (AMP) 3',5' cyclic AMP (cAMP)
5
Coenzymes of dehydrogenases: pyridinic (NAD(P)+), and flavic (FMN, FAD)
N
NN
N
NH2
O
OHOH
HH
CH2
H
C
N
O
NH2
O
OHOH
CH2OPO
O
O
P O
O
O
FMN
NH
N
O
ON
NH3C
H3C
CH2
O
P OH
O
O
P O
OH
OO
N
NN
N
NH2
HO OH
NADHNADPH
FADH2
NAD+
N
NN
N
NH2
O
OHOH
HH
CH2
H
C
N
O
NH2
O
OHOH
CH2OPO
O
O
P O
O
O
H H
N
NN
N
NH2
O
OOH
HH
CH2
H
C
N
O
NH2
O
OHOH
CH2OPO
O
O
P O
O
O
PO
O
ONADP+
N
NN
N
NH2
O
OOH
HH
CH2
H
C
N
O
NH2
O
OHOH
CH2OPO
O
O
P O
O
O
H H
PO
O
O
CHCHCHH2C
OHOHOH
CH2
FAD
NH
NH
O
ON
HNH3C
H3C
CH2
O
P OH
O
O
P O
OH
OO
N
NN
N
NH2
HO OH
CHCHCHH2C
OHOHOH
CH2
NH
N
O
ON
NH3C
H3C
CH2
O
P OH
OH
O
CHCHCHH2C
OHOHOH
NH
NH
O
ON
HNH3C
H3C
CH2
O
P OH
OH
O
CHCHCHH2C
OHOHOH
FMNH2
6
Enzymes-3
Reactions which are catalyzed by the enzymes AST (AsAT, GOT), ALT (AlAT, GPT), LDH, CPK:
Aspartate aminotransferase,AST, AsAT (2)
NH2HC
CH2
COOH
COOH
Aspartic acid
+OC
CH2
COOH
COOH
CH2
ketoglutarate
OC
CH2
COOH
COOH
+NH2HC
CH2
COOH
COOH
CH2
Oxaloacetate Glutamate
Alanine aminotransferase, ALT, AlAT (2)
NH2HC
CH3
COOH
Alanine
+OC
CH2
COOH
COOH
CH2
ketoglutarate
OC
CH3
COOH
+NH2HC
CH2
COOH
COOH
CH2
PyruvateGlutamate
Lactate dehydrogenase, LDH (1)
OHHC
CH3
COOH
Lactate
OC
CH3
COOH
Pyruvate
NADH +H+
Creatine phosphokinase, CPK (2)
CH2
N
COOH
Creatine
ATP ADP
C
NH2
HN
CH2
N
COOH
C
NH
HN
P OH
OH
O
Creatine phosphate
NAD+
CH3CH3
GOT = glutamate-oxaloacetate transaminase; GPT=glutamate-pyruvate transaminase.
7
Isozymes of LDH and CPK:
H H
H H
H H
H M
H H
M M
H M
M M
M M
M M
LDH1 LDH2 LDH3 LDH4 LDH5
(heart) (muscles/liver)(heart/kidney) (kidney) (muscles/liver)
B B B M M M
musclesmyocardiumbrain
CPK-1 CPK-2 CPK-3
8
Biologic oxidation-1
Tricarboxylic acid cycle (TCA), Krebs cycle
Linear design
H2C
C
H2C COOH
COOH
COOH
HO
HC
C
H2C COOH
COOH
COOHCH
HC
H2C COOH
COOH
COOHHO
C
CH2
CH2
COOH
COOH
O C~SCoA
CH2
CH2
COOH
O COOH
CH2
CH2
COOH
COOH
HC
HC
COOH
COOH
CH
CH2
COOH
HO
COOH
C
CH2
COOH
O
H3C CO~SCoA
Oxaloacetate (ОА)
Acetyl-CoA
Citrate Cis-aconitate Isocitrate
-ketoglutarateSuccinyl-CoA Succinate
Fumarate Malate
Citrate synthase (4) Aconitase (4)
H2O
Isocitrate-dehydrogenase (1)
CO2
NAD+ NADH+H+
-ketoglutarate-dehydrogenasecomplex (1,2,1)
[TPP, lipoamide, FAD]
GTPGDP+Pi
Succinyl-CoA-synthetase (6)
FADH2FAD
Succinate-dehydrogenase (1)
Fumarate-hydratase (4)
H2O
Malate-dehydrogenase (1)
Aconitase (4)
H2O
CO2
NAD+ NADH+H+
COOH
C
CH2
COOH
O
OA
NAD+ NADH+H+
HS-CoA
HS-CoA
9
TCA: cyclic design
H2C
C
H2C COOH
COOH
COOH
HO
HC
C
H2C COOH
COOH
COOH
CH
HC
H2C COOH
COOH
COOHHO
C
CH2
CH2
COOH
COOH
O
C~SCoА
CH2
CH2
COOH
O
COOH
CH2
CH2
COOH
COOH
HC
HC
COOH
COOH
CH
CH2
COOH
HO
COOH
C
CH2
COOH
O
H2O
H2O
CO2
NAD+
NADH+H+
CO2
NAD+
NADH+H+
FADH2 FAD
H2O
NAD+NADH+H+
H3C CO~SCoAAcetyl-CoA
HS-CoA
Citrate synthase (4)
Citrate
Aconitase (4)
Cis-aconitate
IsocitrateIsocitrate-
dehydrogenase (1)-ketoglutarate-dehydrogenasecomplex (1,2,1)
[TPP, lipoamide, FAD]
HS-CoA
-ketoglutarateSuccinyl-CoA
GTPGDP+Pi
Succinyl-CoA-synthetase (6)
Succinate-dehydrogenase (1)
Succinate
Fumarate
Fumarate-hydratase (4)
Malate
Malate-dehydrogenase (1)
Oxaloacetate (ОА)
10
Scheme of biologic oxidation substrates formation
FatsCarbohydratesProteins
Glucose
3-PGA
Pyruvate
Acetyl-CoAOxalo-
Acetate
mitoETC
AA Glycerol FA
TCA
ATP
+CO2 -CO2
GlucoseAA Glycerol FA
I stage
II stage
III stage
11
Biologic oxidation-2
Mitochondrial electron-transporting chain (ETC) organization
12
Scheme of microsomal ETC
13
Scheme of reactive oxygen species (ROS) formation. Reactions catalyzed by catalase, superoxide dismutase, glutathione peroxidase; Fenton and Haber-Weiss reactions
Catalase
H2O2 H2O O+catalase (Fe2+)
Superoxide dismutase (SOD)
Glutathione peroxidase (GPx)
2GSH + H2O2 GS-SG + 2H2O.
Fenton reaction
H2O2Fe2+ Fe3+
e-
++ +OH- OH•
hydroxyl-radical
t1/2= 10-9sHaber-Weiss reaction
H2O2O2•- OH- OH•O2+ + +
H+2+ H2O2 O2+
e-
O2•- O2
•- +
e-
SOD(Zn, Mn)
GPx (Se)
Hydroxyl-radical formation
Antioxiant defense (AOD) enzymes
O2 + e- O2•-
Formation of superoxide anion-radical
