*The midterm review session is on 30th October, Monday from 7-9:30pm in 100 Lewis
*Be aware that, on the exam, you might need to illustrate a definition
with a specific example from a particular reaction pathway (this is especially
true of an enzyme or a modification like phosphorylation or a reaction
class like oxidative decarboxylation). In other cases, you might
need to draw a particular structure (such as a phosphoanhydride or ketone
body).
I've given a few guidelines below but you are responsible for
preparing the specific examples wherever applicable.
Chapter 14: Bioenergetics
First law of thermodynamics: In all physical or chemical processes, energy is neither created nor destroyed. It can only be changed from one form to another.
Second law of thermodynamics: In all chemical or physical processes,
the entropy of the universe, S, tends to increase.
*remember that for a reaction to be favorable, the TOTAL entropy change
has to be positive i.e the entropy change of the system and the
surroundings. For example, during protein folding in solution, the protein
(system) becomes more ordered but the water molecules (surroundings) that
are freed up are more disordered. So, overall, protein folding has a large
positive entropy change.
Anabolism: The metabolic phase during which the energy-requiring
biosynthesis of cellular components from smaller precursors takes place.
* In general, anabolic processes consume ATP and therefore require
a high energy charge in the cell.
Catabolism: The metabolic phase during which the energy-yielding
degradation of nutrient molecules takes place.
* These processes require ATP and tend to be driven by low energy charge
in the cell. The exception is protein catabolism where 3 ATP are consumed
for each molecule of urea that is formed (p. 237).
Standard free energy change, DGo:
The free energy change for a reaction occurring under a set of standard
conditions, i.e.. 298K temperature, 1 atm pressure, all solutes at 1 M
concentration.
DGo'
refers to free energy change at pH 7 and 55.5 M [water] which are biological
conditions.
* keep in mind that DGo'
is a constant for a given reaction under given conditions (sort
of like pKa) and that DGo'
is defined as Go'products - Go'reactants
for a reaction.
Endergonic reaction: A chemical
reaction which consumes energy and therefore has a positive DG.
Doesn't occur spontaneously.
Exergonic reaction : A chemical
reaction which proceeds with the release of free energy and therefore has
a negative DG.
Occurs spontaneously.
* Remember that DG
and not DGo'
determines whether a reaction is spontaneous or not.
Autotroph: An organism which synthesizes
its own complex molecules from simple carbon and nitrogen sources such
as CO2 and ammonia.
Chemotroph: An organism that obtains
energy by metabolizing organic compounds derived from other organisms.
High energy bond: A chemical bond
that, upon hydrolysis, undergoes a large decrease in free energy under
standard conditions. The phosphoanhydride bonds in ATP are an example of
a bond that can release a great deal of energy when hydrolyzed.
* However, when we want to couple the energy
released by the breaking of these bonds to drive another normally unfavorable
reaction, just hydrolyzing these bonds won't do. An enzyme or cofactor
is required to covalently link the high-energy bond containing molecule
to the substrate or transition state intermediate so that the favorable
decrease in G can be harnessed to drive the unfavorable reaction.
Transfer potential: A measure of
the ability of a compound to donate an activated group (such as a phosphate
or acyl group).
* If a compound has a high transfer potential
for a group (or an electron), it means that it is higher energy relative
to the species lacking that group. This could be due to destabilization
of the compound or stabilization of the species lacking the group or both
(as is the case with ATP vs. ADP and AMP).
Pyrophosphate (PPi), phosphate anhydride:
Look up structures in textbook (p. 508, fig. 14-12). Pyrophosphate
is a pure (symmetric) phosphate anhydride.
Hydride ion - H- i.e
a species that is essentially H+ + 2e-. *If a net hydride
ion is removed from a compound, that is equivalent to oxidizing the compound,
and if a net hydride ion is added to a compound, that is equivalent
to reducing the compound.
Energetically coupled reactions:
Two chemical reactions that have a common intermediate and thus a means
of energy transfer from the exergonic reaction (such as ATP hydrolysis)
to drive the endergonic one forward.
Energy charge: An index of the
capacity of the adenylate system to provide high transfer potential phosphoryl
groups from phosphoanhydride bonds to drive thermodynamically unfavorable
reactions: ½ {(2 [ATP] + [ADP ])/([ATP] + [ADP] + [AMP])}
Ranges from 0 to 1. (Refer to handout
given by Prof. Penhoet)
Reduction potential, E: A measure
of the relative tendency of the reducing agent to lose electrons.
Electron carrier: A protein that
can reversibly gain and lose electrons, and functions in the transfer of
electrons from organic nutrients to oxygen or some other terminal acceptor.
* Usually the protein contains a flavin
group or Fe-S center that actually carries out the redox reaction.
Relationship between DGo'
and Keq: DGo'
= -RT ln Keq
Central role of ATP: pp. 504
- 509
Structural basis of high group transfer
potential of ATP, 1,3 BPG, PEP:
ATP: High concentration of negative
charge over the phosphoanhydride groups leads to electrostatic repulsion,
the products of ATP hydrolysis i.e.. PPi and Pi are resonance stabilized
and ADP/AMP have less bond strain due to less electrostatic repulsion.
1,3 BPG: Hydrolysis (and therefore
phosphoryl transfer to ADP) of 1,3 BPG to 3-phosphoglycerate is favored
because the product 3-phosphoglycerate has two equally probable resonance
forms. (Refer p. 502, fig. 14- 4)
PEP: PEP has no tautomeric form
but its hydrolysis product pyruvate does. Hence hydrolysis to pyruvate
with the concomitant transfer of a phosphoryl group to ADP is favored.
(Refer p. 502, fig. 14-3)
How NADH and FADH2 serve
as electron carriers: pp. 518 - 521
Structures of ATP, NAD, FAD - from
Chapter 14.
Relationship between redox potential,
E and free energy, G: DG
= -nF DE
where n is the number of electrons transferred and F is Faraday's constant
= 96,480 J/V.mol
Chapter 15: Glycolysis
Glycolysis: The catabolic pathway
by which one molecule of glucose is converted to two molecules of pyruvate
with the net production of 2 molecules of ATP and 2 molecules of NADH.
The balanced reaction for glycolysis is:
Glucose + 2 NAD+ + 2ADP + 2Pi ->
2 Pyruvate + 2 NADH + 2ATP + 2H+ + 2H2O
Kinase: An enzyme that catalyzes
the phosphorylation of molecules
*In general, either ATP is used by the
kinase to phosphorylate the substrate or a compound with high phosphoryl
transfer (PEP, 1,3-BPG) is used by the kinase to phosphorylate ADP into
ATP.
Lactic acid fermentation: The anaerobic
conversion of pyruvate to lactate without any net oxidation.
Pyruvate + NADH + H+ -> Lactate
+ NAD+
*The NAD+ produced is used up in the conversion
of glyceraldehyde-3-phosphate to 1,3-BPG and therefore keeps the payoff
phase of glycolysis going.
Isomerase: An enzyme that catalyzes
the transformation of compounds into their positional isomers.
Aldolase: An enzyme that catalyzes
the reverse of an aldol condensation i.e.. converts an aldol (F1,6P) into
its constituent alcohol (dihydroxyacetone phosphate) and aldehyde (glyceraldehyde-3-phosphate).
Enolase: An enzyme that catalyzes
the reversible removal of a molecule of water from 2-phosphoglycerate to
yield PEP.
Mixed anhydride: An anhydride with
the structure R1-X-O-X-R2 where X= either C or P
|| ||
O O
and R1 is not the same as R2.
Chapter 16: The TCA Cycle
Condensation: The chemical reaction
that converts two reactants into a single product i.e.. the reaction of
acetyl CoA (2-C) with oxaloacetate (4-C) to give citrate (a 6-C compound).
Dehydration: Removal of water across
a bond usually leading to the formation of a double bond, such as the conversion
of citrate to cis-aconitate by aconitase.
Hydration: Addition of water across
a double bond, i.e.. cis-aconitate -> isocitrate
Oxidative decarboxylation: An irreversible
oxidation process in which the carboxyl group is removed from a compound
(such as pyruvate) as a molecule of CO2. *A reduced intermediate
like NADH, NADPH or FADH2 is usually generated as a byproduct.
Thioester bond: An ester of a carboxylic
acid with a thiol or mercaptan. Has higher standard free energy of hydrolysis
that a normal ester bond due to lack of resonance stabilization of the
thioester ( refer p. 503, fig. 14-7)
Substrate level phosphorylation:
Phosphorylation of ADP or some other nucleoside 5'-diphosphate coupled
to the dehydrogenation of an organic phosphate; independent of the electron
transfer chain.
Cofactor, prosthetic group: An
organic compound (other than an amino acid) or a metal ion that is covalently
bound to a protein and is essential for its activity.
Product inhibition: Inhibition
of a pathway through the negative modulation of the enzyme catalyzing it
by the end product of the pathway. For example, acetyl CoA inhibits pyruvate
dehydrogenase.
Chapter 17: Fatty Acid Oxidation
Beta-oxidation: Oxidative degradation
of fatty acids into Acetyl CoA by successive oxidations at the beta-carbon
atom of the fatty acid chain.
Acyl carnitine/ carnitine transporter
(definition suggested by Samina Ayub - thanks!): A transporter
system located on the inner mitochondrial membrane that carries out the
facilitated diffusion of fatty acyl CoA into the mitochondrial matrix
by the temporary transesterification of fatty acyl CoA to the hydroxyl
group of carnitine. Once inside the matrix, the fatty acylCoA is removed
and undergoes beta-oxidation, and the regenerated carnitine is transported
back to the mitochondrial intermembrane space. Fig. 17-6 on p. 603 describes
the process.
Saturated fatty acid: A fatty acid
containing a fully-saturated alkyl chain i.e an alkyl chain with no double
C-C bonds.
Unsaturated fatty acid: A fatty
acid containing one or more double bonds.
Ketone bodies: Water-soluble fuels
normally exported by the liver but overproduced during fasting or during
untreated diabetes mellitus. Acetoacetate, hydroxybutarate and acetone
are the ketone bodies produced. (structures on p. 616, fig. 17-16)
Chapter 18: Amino Acid and Urea Metabolism
Transaminase: Enzyme that catalyzes
the transfer of amino groups from a-amino
to a-keto acids. (also called aminotransferases).
Pyridoxal phosphate (PLP): A coenzyme
containing the vitamin pyridoxine (vitamin B6) which functions in reactions
involving amino group transfer.
* He may have accidentally referred
to PLP as TPP during one point in the lecture.
** Pyridoxal phosphate has two forms ie.
PLP and its aminated form, pyridoxamine phosphate.
Pyridoxal phosphate is involved
in amino acid catabolism (accepts the amino group) whereas pyridoxamine
phosphate is involved in amino acid anabolism (transfers amino
group to synthesize amino acid).
Carbamoyl phosphate: Product formed
from the ammonia generated in the liver mitochondria during amino acid
catabolism through its reaction with CO2 formed during mitochondrial respiration
(in the form of bicarbonate).
* refer p. 635, fig. 18-10
Ketogenic amino acid: Amino acids
with carbon skeletons that can serve as precursors of the ketone bodies.
* Trp, Phe, Tyr, Ile, Leu and Lys are
ketogenic and can be degraded into acetoacetyl CoA or acetyl CoA.
Glucogenic amino acids: Amino acids
carbon chains that can be metabolically converted into glucose or glycogen
via gluconeogenesis.
* Ala, Cys, Gly, Ser, Trp, Asp, Asn, Phe,
Tyr, Ile, Met, Thr, Val, Arg, Gln, His, Pro are glucogenic since they are
degraded to pyruvate, a-ketoglutarate, succinyl CoA, fumarate and/or oxaloacetate
which can then be converted to glucose and glycogen
** Please note that Trp, Phe, Tyr and
Ile are both ketogenic and glucogenic.
(refer p. 654, fig. 18-29)
Chapter 19: Electron Transport and
Oxidative phosphorylation
Multienzyme complex: A group of
related enzymes participating in a given metabolic pathway.
* Other than the electron transport chain
complex, recall that the three-enzyme pyruvate dehydrogenase complex is
also an example.
Oxidative phosphorylation: The
enzymatic phosphorylation of ADP to ATP coupled to electron transfer from
a substrate to molecular oxygen.
Mitochondria: Membrane-bound organelles
in the cytoplasm of eucaryote which contain the enzyme systems required
for TCA cycle, fatty acid oxidation, electron transfer and oxidative phosphorylation.
Cristae: Infoldings of the inner
mitochondrial membrane.
Matrix: 1) The aqueous contents
of a cell or organelle with dissolved solutes.
2) An artificial reality that unfortunately cannot be explained but must
be seen for oneself (as told to Keanu Reeves
by Laurence Fishburne)
Electron transfer potential: A
relative measure of the ability of a compound to transfer electrons to
another compound in an electron transport chain. The higher the reduction
potential of a compound, the less likely it is to transfer electrons.
Redox couple (redox pair): An electron
donor and its corresponding oxidized form. For example, NADH and NAD+
Half-cell reaction: The stoichiometric
halves of a redox reaction explicitly containing the number of electrons
transferred during the reaction; allows one to examine the reduction and
oxidation reactions separately.
Quinone: Generic name for one or
several fused oxidized phenol rings. (I got this definition out of "Organic
Chemistry" by M. Loudon, and we'll stick with it unless Prof. Penhoet gives
us a better one). Example is ubiquinone which is an intermediate
electron carrier in the mitochondrial electron chain.
Cytochrome: Heme protein serving
as an electron carrier in respiration, photosynthesis, and other oxidation-reduction
reactions.
Respiratory chain, or the electron
transfer chain: A sequence of electron-carrying proteins that transfer
electrons from substrates to molecular oxygen in aerobic cells.
Cytosol: The continuous aqueous
phase of the cytoplasm with its dissolved solutes; excludes the organelles
such as the mitochondria.
Thermodynamic efficiency: The ratio
of useful work generated to the energy added to a system.
*Can range from 0 to 1, though in practice
processes never have an efficiency of 1 due to dissipation of some free
energy as heat (ie. systems never achieve 100% efficient energy transfer).
Chapter 20: Carbohydrate biosynthesis
Tandem enzyme (hybrid enzyme): A single, bifunctional protein containing two distinct enzymatic activities. An example is the PFK-2/FBPase-2 complex * (refer pp.732 -733, Fig. 20-8)* which carries out both the formation and breakdown of the allosteric PFK-1 stimulator, fructose-2,6-phosphate (F-2,6-P).
Malate shuttle: A shuttle system found in the heart, liver and
kidney that is used for transporting reducing equivalents from cytosolic
NADH into the mitochondrial matrix via malate (reduced form of oxaloacetate),
where they can be passed through the electron transport chain to O2
thereby producing 2.5 ATP/pair of electrons transferred.
* Refer p. 685, Fig. 19-26. The malate produced in the intermembrane
space by the reduction of oxaloacetate is carried into the mitochondrial
matrix by the malate-a-ketoglutatarate
transporter. Inside the matrix, malate transfers electrons to NAD to form
NADH which participates in the electron transport chain. The oxaloacetate
regenerated inside the matrix is transaminated to aspartate which is carried
out into intermembrane space by the glutamate-aspartate transporter and
de-aminated back to oxaloacetate.
Phosphotase: An enzyme that catalyzes the hydrolysis of a phosphate
ester or anhydride, releasing inorganic phosphate.
* There are dozens of phosphatases we have encountered - phosphorylase
a phosphotase, FBPase etc... so just pick a few as examples.
Kinase: An enzyme that catalyzes the phosphorylation of certain
molecules by ATP.
* Again, pick a few examples - the glycolytic pathway is chock-a-block
with kinases....
Futile Cycle: A set of enzyme-catalyzed cyclic reactions
that results in release of thermal energy by the hydrolysis of ATP, without
any net metabolic work being done. *An example would be the simultaneous
progression of gluconeogenesis and glycolysis at the F-6-P/F-1,6-P step
- refer pp. 730-731. Also simultaneous fatty acid synthesis and b-oxidation
is another example.
* Reciprocal regulation is one way to prevent setting up futile cycling.
You should understand this on the level of regulation of F-2,6-P
formation and degradation - pp.731-732
Primer: A short oligomer (of sugars or nucleotides) to which an enzyme can add additional monomeric units. For example, the enzyme glycogenin acts as a primer for ab initio glycogen synthesis via its Tyr group - * refer p. 738, Fig. 20-14
Synthase: An enzyme that catalyzes condensation reactions in
which no nucleoside triphosphate is required as an energy source.
*Glycogen synthase (p. 738) is an example.
Phosphorylase: An enzyme that catalyzes the cleavage of a compound
with phosphate as the attacking group (i.e. phosphorolysis).
* Again, glycogen phosphorylase is an example.
Nucleotide sugar: A compound in which the anomeric carbon of
a sugar is activated by attachment to a nucleotide through a phosphodiester
linkage.
* Refer p. 735, Fig. 20-11 for structure and properties that
make them suitable for biosynthetic reactions.
* One important property is that their formation is metabolically irreversible,
thereby making the synthetic pathways they participate in irreversible
too.
Chapter 21: Lipid Biosynthesis
Multienzyme complex: A group of
related enzymes participating in a given metabolic pathway.
* Study the fatty acid synthase seven-enzyme
complex (p. 777) - the active site of each enzyme is positioned
in close proximity to the active sites of enzymes preceding and succeeding
it in the complex.
Acyl carrier protein (ACP): A small
9 kD protein that carries acyl groups in a high energy thioester linkage
which, when hydrolyzed, releases energy that makes the first reaction in
fatty acid synthesis (the condensation of acetyl CoA with malonyl CoA)
thermodynamically favorable.
* The structure is shown on p.
773., Fig. 21-4
Malonyl CoA: A three-carbon intermediate that participates in the biosynthesis of fatty acids but not their breakdown. * Structure on p. 771, Fig 21-1
Fatty acid: A long chain aliphatic
carboxylic acid found in natural fats and oils; also a component of membrane
phospholipids and glycolipids.
* Know the generic structure of fatty
acids
Phospholipid: A lipid containing
one or more phosphate groups (duh!!)
Chapter 22: Amino Acid and Nucleoside Biosynthesis
Essential Amino Acids: Amino acids that cannot be synthesized
by humans and other vertebrates, and must be obtained from the diet.
For example, Thr, Trp, Val etc. *Refer to Table 18-1, p. 637 for
a complete list of essential and non-essential amino acids
Feedback Inhibition: Inhibition of an allosteric enzyme at the
beginning of a metabolic sequence by the end product of the sequence (also
known as end-product inhibition).
* Palmitoyl CoA-mediated inhibition of acetyl CoA carboxylase (rate-limiting
enzyme of fatty acid biosynthesis) is an example (p. 780, Fig. 21-12).
Another example occurs in the purine biosynthesis pathways shown in Fig.
22-23, p.853.
Structures of adenine, guanine, (purine bases on p. 852), cytosine, thymine, uracil (pyrimidine bases on p. 854) and PRPP (p. 827)
Concerted feedback inhibition: An allosteric regulation mechanism
where the common step of a branched metabolic pathway is inhibited
by overall high levels of its multiple end products.
* An example is glutamine synthetase (Fig 22-6, p.824). Concerted
feedback inhibition behaves like a logical AND gate, for those of you into
that sort of thing.
'Once the whole is divided, the parts need names.
There are already enough names.
One must know when to stop.
Knowing when to stop averts trouble.'
- Lao Tsu
"Tao te Ching"
Good luck, gang!