Enzymes
Number
Size
>104
Coenzymes
15-20
Macromolecules (104 Small molecules (102 to104)
to106)
Proteins
Structure
(ribozymes)
Most are heterocyclic organic
compounds
Building
Blocks
Amino acids
(nucleic acids)
Vitamins, modified amino
acids, nucleotides, metals
Active
Center
Amino acid side
chains, metal
cofactors
Special chemical groups
Always restored to
Chemically changed by
Recycling original form during a enzyme action; Prosthetic
single cycle
groups
1
Acetyl CoA
O
CH3C-SCoA
O
CH3C-X + H-SCoA
Able to recognize
CoASH
Coenzyme A
2
CoA
Acetyl CoA
O
1. An important molecule in metabolism CH3C~SCoA
2. Its main use is to convey the C atoms within the acetyl
group to the TCA cycle to be oxidized for energy
production.
3. In chemical structure, acetyl-CoA is the thioester between
coenzyme A (a thiol) and acetic acid (an acyl group
carrier).
4. Acteyl-CoA is produced during the second step of aerobic
cellular respiration, pyruvate decarboxylation, which
occurs in the matrix of the mitochondria.
Pyruvate dehydrogenase
Pyruvate +NAD+ + CoA---------Acetyl-CoA +CO2 +NADH
NAD+ is a common oxidant
5. C~S is a high energy bond energetically favorable for
group transfer.
6. It has to couple ATP hydrolysis to regenerate.
3
Nicotinamide Adenine Dinucleotide Coenzymes
(NAD; NADP
NADH;NADPH)
NADH
Able to recognize
4
NAD / NADP
1. NAD is a dinucleotide, consists of two nucleotides joined
through their phosphate groups.
2. In metabolism, NAD+ is involved in redox reactions,
carrying electrons from one reaction to another.
3. NAD+ is an oxidizing agent – it accepts electrons from
other molecules and becomes reduced, to form NADH.
4. NADH is a reducing agent – it can donate electrons.
5. Electron transfer reactions are the main function of NAD+.
6. NADPH is NADH with an extra phosphate group on the 2’
site of the ribose ring that carries the adenine moiety.
7. NADPH usually provides the reducing power for
biosynthetic reactions.
5
FAD and FMN
6
Able to recognize
FAD / FMN
1. FAD is a redox cofactor involved in several
important reactions in metabolism.
2. FAD can exist in two different redox states and
its biochemical role usually involves changing
between these two states. FAD can be reduced
to the FADH2, whereby it accepts two H atoms.
3. FMN functions as prosthetic group of various
oxidoreductases such as NADH dehydrogenase.
4. During catalytic cycle, the reversible
interconversion of oxidized (FMN), semiquinone
(FMNH•) and reduced (FMNH2) forms occurs.
5. FMN is a stronger oxidizing agent than NAD+
and is particularly useful because it can take
7
part in both one and two electron transfers.
Metabolism
8
Glycolysis
9
Glycosis
10
GAP dehydrogenase
Aldehyde
Strong oxidant
carboxylic acid
11
ATP production
1,3-BPG is an energy –rich molecule with a greater phosphoryl-transfer potential
than that of ATP. Thus, it can be used to power the ATP synthesis from ADP.
This is called substrate-level phosphorylation because the phosphate donor is a
Substrate with high phosphoryl-transfer potential.
PEP has high phosphoryl-transfer potential, pyruvate (ketone) is much more stable12
than enol form.
Glycolysis summary
•Inputs:
•Glucose
•2 NAD+
•2 ATP
•4 ADP
•2 Pi
•Outputs:
•2 pyruvate
•2 NADH
•2 ADP
•4 ATP
•2 ATP (net gain)
Glucose + 2Pi + 2ADP + 2NAD+ 2pyruvate + 2ATP + 2NADH +2H+ + 2H2O
13
NAD regeneration
14
+O2
-O2
NAD regeneration
15
Transition reaction inputs and
outputs from glucose
•Inputs:
•2 pyruvate
•2 CoA
•2 NAD+
•Outputs:
•2 acetyl CoA
•2 CO2
•2 NADH
Pyruvate dehydrogenase
Pyruvate + NAD+ + CoA
Acetyl-CoA + CO2 + NADH
Link between glycolysis and TCA cycle
16
S-CoA
TCA Cycle
17
Critical steps
Citrate synthase
Oxidation
2nd oxidative
decarboxylation
decarboxylation
isocitrate
dehydrogenase
a-ketoglutarate
dehydrogenase
18
Enery-rich thioester compound
Critical steps
Succinyl CoA
synthetase
Oxidation
Hydration
Oxidation
Oxaloacetate is regenerated for next cycle
Energy is extracted in the form of FADH2 and NADH
19
Citric acid cycle inputs and outputs
per glucose molecule
•Inputs:
•2 acetyl groups
•6 NAD+
•2 FAD
•2 GDP + 2 P
•Outputs:
•4 CO2
•6 NADH
•2 FADH2
•2 GTP
Extremely efficient: conserve 90% of energy
available from oxidation of acetyl CoA
Acetyl-CoA + 3NAD+ + FAD + GDP + Pi + 2H2O
2CO2 + 3NADH + FADH2 + GTP + 2H+ + CoA
20
Fatty acids
Glucose
Pyruvate
Ketone bodies
O
CH3C-SCoA
(2C)
Acetate
Amino Acids
CoASH
4C
NADH + H+
FADH2
Minimal
TCA
6C
NADH + H+
CO2
4C
GTP GDP
NADH +
CO2
H+
1 GTP
3 NADH
+1 FADH2
10 ATP/cycle
And releases
two CO2
NOTE: 1 NADH  2.5 ATP; 1 FADH2  1.5 ATP; 1 GTP  1 ATP so get 1 + 7.5 + 1.5 = 10 ATP/cycle
Will be revisited later in detail!
Metabolism
Harvesting electrons for the Electron transport chain
22
TCA Connections
Acetyl CoA
Amino Acid
Synthesis
Oxaloacetate
Malate
a-ketoglutarate
Succinyl
CoA
Gluconeogenesis
Heme
Fatty Acid
Synthesis
Citrate
Amino Acid and
Neurotransmitter
Synthesis
23