This document reviews basic metabolic principles including: 1. ATP is the primary energy currency of cells and is generated through catabolic pathways and utilized in anabolic pathways. Other energy carriers include NADH, FADH2, and phosphate compounds. 2. Coenzymes such as coenzyme A help transfer chemical groups during reactions and some are derived from vitamins. Metabolic pathways are regulated by products and cellular energy levels. 3. Enzymes are classified based on the reactions they catalyze such as kinases, dehydrogenases, and transferases.

1. Review of Basic Metabolic Principles
A. Energy Currency of the Cell
Metabolic pathways can be classified as either:
• energy generating (catabolic)…or
• energy utilizing (anabolic)
The cell also uses two types of energy currency:
1. Phosphate anhydrides (compounds with high
phosphate transfer potential)
General: hydrolysis of a phosphate ester
O
R O P
OH
O
H2O
O
O H + +
R OH P
OH
O
ATP hydrolysis
O
HO P O
O
O
P
O
O
O P
CH2
O
A
O
OH OH
O
HO P
O
O
O P
CH2
O
A
O
OH OH
O
HO P O
O
H2O
+ + H
ATP

2. Free Energies of hydrolysis of some phosphorylated
compounds
Compound ΔG°’ (kcal/mol)
Phosphoenolpyruvate -14.8
Carbamoyl phosphate -12.3
Acetyl phosphate -10.3
Creatine phosphate -10.3
Pyrophosphate -8.0
ATP (to ADP) -7.3
Glucose 1-phosphate -5.0
Glucose 6-phosphate -3.3
Glycerol 3-phosphate -2.2
ATP is the most commonly used compound with
high phosphate transfer potential
• phosphoenolpyruvate & creatine phosphate
have enough energy to synthesize ATP
• ATP can be used to synthesize glucose 6-
phosphate & similar compounds
GTP is sometimes used in place of ATP

3. ATP is called the energy currency of the cell
Catabolism Anabolism
O2
Foods ATP
CO2 + H2O [Energy]
Work
Heat
Biosynthesis
Definitions:
• catabolism is the production of energy from
food
• anabolism is the utilization of energy to provide
heat, do work, or drive biosynthetic reactions
2. Reducing equivalents (compounds with high
electron transfer potential)
Foods → NADH and FADH2 → ATP for Biosynthesis
The reducing equivalents in the foods we eat…
• are transferred to NADH and FADH2
• NADH and FADH2 transfer their electrons to
the electron transport chain which..
• uses the energy in those electrons to synthesize
ATP

4. Based on what you already know, you might predict
that:
• catabolic pathways produce NADH, FADH2, &
ATP
• anabolic pathways utilize ATP, NADH, & FADH2
However, that’s not quite true. In reality:
• catabolic pathways produce NADH, FADH2, &
ATP
• anabolic pathways utilize ATP, NADPH, & FADH2
B. Coenzymes
1. Definition
Coenzymes are small molecular weight
compounds that are:
a. necessary for the catalytic activity of
one or more enzymes
b. present in very small amounts compared
to the substrates of the enzyme
c. used over & over in a catalytic manner
• most coenzymes exist free in solution
• some coenzymes are bound to proteins
= prosthetic groups

5. 2. Coenzymes carry some biologically important
chemical group in an “activated” (high energy)
form so that it can be used in biosynthetic
reactions
Example = coenzyme A (carries acyl groups)
O
CH3 C
SCoA + H20
O
CH2 C
+ CoASH
OH
acetyl CoA acetic acid
G = -7.5 kcal/mole
O
R C
SCoA
acyl CoA
+ H20
O
C
OH
R
+ CoASH
carboxylic acid

6. 3. Coenzymes are sometimes derived from vitamins
Some activated carriers in metabolism
Carrier
Molecule
Group carried
in activated
form
Vitamin source
of coenzyme
ATP Phosphoryl
NADH &
NADPH
Electrons Niacin
FADH2 &
FMNH2
Electrons Riboflavin
Coenzyme A Acyl Pantothenic
acid
Lipoamide Acyl
Thiamine
pyrophosphate
Aldehyde &
Ketone
Thiamine
Biotin CO2 Biotin
Tetrahydro-folate
1-carbon units Folic acid
S-adenosyl-methionine
Methyl
UDP glucose Glucose

7. C. What Does a Metabolic Pathway Look Like?
• many reversible reactions
• a few irreversible reactions that drive the
pathway
• the irreversible reactions are important!
A B C D E F
E1 E2 E3 E4 E5
D. Control of Metabolism
1. Controls Which Operate at a Cellular Level
• regulation is by inhibitors & activators in cell
a. Which metabolites usually regulate pathways?
i. The precursor of a pathway usually
stimulates the pathway
+
A B C D E
ii. The end product of a pathway usually
inhibits the pathway
-
A B C D E

8. iii. The end product of a competing pathway
often stimulates the other pathway
A B C D E
+
G
H
I
iv. Energy utilizing & producing pathways
are often regulated on the basis of
ATP supply in the cell
• Catabolic pathways are inhibited by
ATP and/or stimulated by ADP or AMP
• Anabolic pathways are stimulated by
ATP and/or inhibited by ADP or AMP
b. Where are pathways regulated?
i. At or near a branch point
A
B
D
C
*
*

9. ii. At 1st committed (irreversible) step
A B * C D E
2. Controls that operate at whole body level
• sites of regulation similar, but mechanisms different
a. Peptide hormones (glucagon, epinephrine,
& insulin)
• act via second messenger (eg, cAMP)
• result in phosphorylation or dephosphoryl-ation
• alter enzyme activity
• are fast acting
b. Steroid hormones (cortisol)
• travel to nucleus & bind to DNA
• affect amount of enzyme made
• are slower acting

10. E. Glossary of Enzyme Names
Kinase: catalyzes the phosphorylation of some
metabolite, usually with ATP as the donor
Example = glucokinase or hexokinase
ATP + glucose → ADP + glucose 6-phosphate
Phosphatase: catalyzes the hydrolytic removal
of a phosphate group (also called
dephosphorylation)
Example = glucose 6-phosphatase
glucose 6-phosphate + H2O → glucose + Pi
Phosphorylase: catalyzes the phosphorolytic
cleavage of a bond (phosphate is the
attacking nucleophile)
Example = glycogen phosphorylase
+
O O
Pi O
O
O
O O
HO O
O
OPi

11. Hydrolase: catalyzes the hydrolytic cleavage of
some bond (water is the attacking nucleophile)
Often subclassified according to bond cleaved
Esterase: hydrolyzes ester bond
Peptidase: hydrolyzes peptide bond
Phospholipase: hydrolyses phospholipids
Dehydrogenase: catalyses oxidation-reduction
reactions by the transfer of hydrogens
(electrons). Generally use NAD+/NADH or
FAD/FADH2.
Example = lactate dehydrogenase
CH3
C O
-
CO2
+ NADH + H+
Pyruvate + NADH + H+
NAD+ +
CH3
CHOH
-
CO2
NAD+ + Lactate
Synthetase or synthase: catalyzes the joining of
two molecules to create a larger molecule
Example: citrate synthase
oxaloacetate + acetylCoA + H2O → citrate + CoASH
(4 carbons) (2 carbons) (6 carbons)

12. Carboxylase: catalyzes the addition of CO2 to a
molecule. Uses biotin as a coenzyme
Example = pyruvate carboxylase
pyruvate + CO2 + ATP + H2O OAA + ADP + Pi
O
O
Transferase: catalyzes the transfer of a group from
one molecule to another. Subclassified
according to group transferred
Transaminase: transfers amino groups. Uses
pyridoxal phosphate as a coenzyme.
Example = aspartate transaminase (AST)
+
-ketoglutarate Aspartate Glutamate
+
Oxaloacetate
CO2
-
CH2
CH2
C O
CO2
-
CH2
CH
CO2
-
CO2
-
NH3
+
CO2
-
CH2
CH2
CH NH3
+
CO2
-
CO2
-
CH2
C O
CO2
-
O
C
O
C
CH3
O
C
O
C
CH2 C
O
O
pyruvate oxaloacetate

13. Transaldolase: transfers aldehyde groups. Uses
thiamine pyrophosphate as a coenzyme
aldehyde:
R C
O
H
Transketolase: transfers ketone groups. Uses
thiamine pyrophosphate as a coenzyme
ketone:
O
R C CH3
Acyltransferase: transfers acyl (carboxylic acid)
groups. Uses coenzyme A as a coenzyme
acyl (carboxylic acid):
R C
O
OH
Methyltransferase: transfers methyl groups.
Decarboxylase: removes carboxyl groups as CO2
Isomerase: converts from one isomer to another