Final study guide:

1st midterm

Biomolecule diversity and complexity, and underlying simplicity

Physical and solvent properties of water
Weak acids and bases
Keq, Kw, pH, pOH, Ka, pKa
Henderson-Hasselbalch equation
Acid/base titration curves
Buffers
Stereochemistry, especially Fisher
Amino acids: structures, names, 3- and 1-letter abbreviations, physical properties, pKa’s
Factors affecting pKa
Molecular and solution charge states, isoelectric point
Peptide naming
Peptide bond, peptide plates, ϕ and ψ dihedral angles, Ramachandran plot
Orders of protein structure, interactions important in protein structure
Protein sequence similarity
Features of secondary structures (α-helix, β-turn, β-sheets), amino acid propensities
Protein structure motifs (tertiary structure)
Protein denaturation
Features of fibrous proteins, structures of collagen and keratin
Features of globular proteins
Conjugated proteins, carbohydrates, lipids
Carbohydrate classification and basic nomenclature
Stereochemistry of carbohydrates (incl. anomers, epimers, enantiomers, D/L)
Carbohydrate structure (those for quiz, plus NAG; also be familiar with polysaccharides),
conformation & interactions
Carbohydrate chemistry: cyclization, glycosidic bond, reducing vs. non-reducing
Structural vs. storage polysaccharides
Lipid structures and properties: fatty acids, triacylglycerols, glycerophospholipids, sphingolipids,
cholesterol
Lipid naming: common (compendium p.46 only), delta and omega naming for fatty acids; basic
lipid nomenclature (compendium p.50)
Lipid aggregation in solution
Features of membrane proteins
Structure, features, and dynamics of biological membranes

2nd midterm:
Chapter 6: Enzym
16.1 Introduction to enzymes

Introduction to Enzyme Catalysis

Kinetics of Enzyme Catalysis
Linear plots of enzyme knetic date and their interpretation
Factors affecting enzyme activiy and
effect on inhibirotrs on enzyme kinetics
mechanims of enzyme catalysis
regulation of enzyme catalysis
sigmoidal knietcis
myoglobin
hemoglobin
bioenergetics
currencies of energy trasnduction

3rd Midterm
Topics
Chapter 15:
- Metabolism basics
-all synthetic and degraditve reactions occurring in living cell
-catabolsim- degradation of biomolecules to get biological intermediates while
also extracting energy and reducing power
- primarily uses NAD as electron acceptor
-anabolism- utilization of energy reuding pweor and small molecules
-use products of catabolism for synthesis of biological molecules
-biosyntheisis of amino acids, fatty acids, nucleotides
-macromolecular syntheis and growth (lipids, membranes, proteins, etc)
-meatbolic reaction= enzyme catalyzed organic reactions (
-metabolic pathway characteristics
-regulated
-each pathway has a 1st committed step athat is usually high spontaneous,
regulated and rate limiting
-most have intermediate rnx btwn committed step and final and are usually
readily reversible
-independent pathways (different set of reactions) for opping pathways
allow indepent and coordinated regualtion
pathway thermodynamics and regulation of interconversion
-couple unfavored reactions to highly favored

- Energy carriers
-NAD(NADP)+. NADH (NADPH
CHAPTER 14
14.1 Glycolysis- a molecule of glucose degraded in a series of 10 enzyme catalyzed reactions
into 2 molecules of pyruvate, realeading free engery that is stored in ATP and NADH
-Glycolysis Stage I- prepatory stage- 2 molecules of ATP consumed
glucose + 2 atp -> 2 glyceraldehyde + 2 ADP + 2 H+
 Reactions:
1. Phosphorylation of Glucose (irreversible, -17 kj, very spontaneous)
-glucose is phosphorlyated at C-6 -yields glucose 6 phosphate with
ATP as phosphoryl donor
-hexokinase, which has a specific type of induced fit where glucose must
bind which cause conformatioanl change that blocks excess of
water from active stie
-has isozyme, glucokinase, which binds excess glucose in the liver and is
regulated by substrate availbiilty ( like sigmoid curve but
monomeric enzyme)
- requires Mg2+ for activity
-positive- Pi negative-glucose -6-phosphate
2. Isomerization of g-6p (G6P + mg2+ -> fructose 6 phospate (readibly reversible)
-primes substrate for phos at C-1 (more favorable for -0h)
-activates c-3 for aldol cleaveage
3. Phosphorylation of f-6-P
-F-6-P +ATP  fructose-1,6 bispohsphate + ADP +H+
-enzyme is phosphofuctrokianse (PFK)
-commitming step of carbons to catabolism
- major regulatory step, and alos rate limiting
-PFK very sensitve to energy status of cell (neg effectors are ATP, citrate,
H+; positive are amp adp, pi, fructose 2,6 bisphosphate
4. Cleavage of F 1,6 bisP intro trioses
- fructose 1,6bis P  dihydroxyacentone phsphate + glycaraldehyde 3-p
- has postive stand G but actual G is slightly negative under phyi codition
as long as concentration of two products I kept low by their
utilzation in other biolocigal reations
-aldolase mech proceeds through a Schiff base covalent intermediate
5. Isomerization of DHAP to glyceraldehydes 3 phospate
catalyzed by triose phosphate isomerase (TIME) cataly. Perfect enzyme
- so efficient at binding substare and catalyzing that the product is formed
as soon as substrate collides with active site
- readily reversible
-similar to step 2 of glycolysyis, just doing opposite
-
-Glycolysis stage II reactions (Payoff phase)- yields ATP and NADH
6. Oxidation and phos of g-3-p to 1,3 bisphosphoglycerate (enzyme= G-3P dehydrog)
G-3-P + NAD+ + Pi  I, b bisphosphoglycerate + NADH + H+
Readily reversible, the next rxn is highly spontaneous so it pulll this one forward
under intracellular conditions by removal of product
7. Ttransfer of pohsphryl group from 1,3BPG to ADP to form ATP
1,3BPG + ADP + mg2+  3 phosphoglycerate + ATP
- catalyze by phosphoglycerate kinase
-substrate level phospohrylation because it involes soluble enzyme and chemical
intermediates
8. Isomerization of 3 PGA to 2 PGA
 - posphoglycerate mutase
-readily reversible, has two steps uses active site His
9. Dehydration of 2PG to phosphoenolpyruvate (PEP)
- enolization, cat, by enolase
-readily reversible
-has intermediate stabl by Mg 2+
10. Transfer of phos group from PEP to ADP to form ATP
PEP + ADP + Mg 2+ + K+ + H  pyruvate +atp
Cat by pyruvate kinase
-second substrate level phospohylation
-very spontaneous
pos eff- amp, adp, fruc 1,6 bispohsphate
neg eff- ATP, acetyl-Coa, nadh, alanine, long chain fatty acids
-also regulated by pospoohylation (phos form is inhibited, dephos is active)
NET: glucose + 2adp = 2 pi + 2 nad  2 pyruvate + 2 ATP + 2NADH+ 4H + 2H2O
-
- Fermentation (lactic acid and ethanol)
- G
14.3 Fates of pyruvate under anaerobic conditions: fermentation
-w/out oxygen NADH cant be regenered to NAD, which would stop glycolysis
-trasnfer electrons from NADH to form a reduced end product –lactic acid/ethanol
A. Lactic Acid Fermentation
-NAD regernetated by reduction of pyruvate to lactate
-catalyzed by lactaste dehydrogense
pyruvate + NADH = H  L-lactate + NAD produced 2 ATP /glucose
- no net change in oxidation state of carbon
-fermentation- processes that extract energy but do not consume oxygen or
change concentration of NAD/NADH
B. Ethanol Fermentation
-two step process
1. pyruvate is decarboxylated in irreversible rxn catalyzed by pry decarboxylase
2. acetaldehyde is reduced to ehanol through alcohol dehydrogenase
overall- glucose + 2 adp + 2 pi 2 etahnol + 2 co2+ 2 atp + 2 h2O
3 irreservible reactions in gly: step 1, 3, and 10 (glucose to G6P; F6P to F1,6bisP, PEP to
pyruvate

14.4 Gluconeogenesis
-bypass the 3 iir steps by separate set of enzymes that are also irreverisve
net - 2 pyr + 4 atp + 2 gtp + 2nadh +2h + 2H2O glucose + 4adp + 2gdp + 6 pi+ 2 nad
-liver, kidney and small intestineprovides glucose for brain, muscles
A) Conversion of phyruvate to PEP requires to exergonic reactions
-pyruvate decarboxylase (stimulated by acetyl CoA)
-pyruvate to OAA to malate to PEP
overall rxn – pyruvate + ATP + GTP + HC03-  PEP + ADP + GDP+ pi + Co2
B0 Conversion of F16BisP to Furctose 6 phsphate
F1,6bisP + h20  f6P + pi
 -enzyme= fructose 1,6 bisphosphatse (FBPase-1)
C) glucose 6 P to glucose
G6P + H2O  glucose + pi catalyzed by Mg2+ and glucose 6 phosphatase
Reciprocally regulated so no wasteful producion of heat
- regulated allosterically and by phsophorylation

Chapter 15
- Reduction potentials
- Oxidation reduction reactions

Chapter 16: Citric Acid Cycle-

Aerobic metabolism carbosn of glucose are fully oxidized to CO2
-takes place in mitochondrial matriz and conties to inner membrance

16.1 Pyruvate dehydrogensase complex- production of acetyl coa

16.2 TCA Cycle Reactions and Enymes

-to begin trun of cyle, acetyl CoA donates it acetyl group to the 4 carbon oxaloacetate
A) Has 8 steps
1. Formation of Citrate
-condensation of acetyl-CoA with OAA to form citrate, cat citrate synthase
2. Formation of Isocitrate via cis Aconitate
-aconitase catalyzes reversible trasn of citrate to isocitrate through intermediate
cis aconitate
- goes to right because isocitate is rapidly consumed in net step, lowiering steady
state concentration
- three point bidning of substarte orients it so hydrozyl gropu always moves to end
of molecule that originated from OAA not end that originated from acetyl group
3. Oxidation of Isocitrate to a ketoglutarate and Co2
-isocitrate dehydrogenase catalyzes oxidative decarb of isocitrate
-first is oxidized by hydire transfer to NAD, then decarboylated
intermediate is oxalosuccinate
4. oxidation of a keto to succinyl coA and CO2
-another oxidative decrb by a keto dehydrogenase complex
-NAD is electron acceptor and COA carries syccinyl group
-very similar to pdh complex
5. conversion of succinyl to Succinate
-succinyl Coa synthetase breaks thioester bond, which is coupled to synthesis of
GTP forming Succinate in the process
-uses step wehre enzyme becomes phospohrylated at His residue
6. oxidation of Succinate to fumarate
-flavoprottein Succinate dehydrogenase is enzympe, reduces FAD to FADH2
 -only membrance boud enzympe of TCA cycles, part of Complex II
7. hydration of fumarate to L-malate
-reversible hydration catalyzed by fumarase (lyase)
8. oxidat ion of malate to OAA
-Nad linked malate dehy oxidizes malae
-lies far to left, but OAA is continually being removed by step 1, so conctration of
OAA is really low, pulling reaction to the right
-for each turn, 2 NADH, one FADh2, one GTP and two CO2 are released
- steps 1,3 and 4 are essentially irreversible
-OAAproduced from aspartate, a keto gultarate from glutamate
B) Amphibolic pathway
TCA intermiedates are utilized as precursors for biosytnesis
-vauriosu pathways generate intermediates
-oxidation of odd chain fatty acids get succinyl coA, (so does degradation of ile,
met, val)
-degradation of some aa yield fumarate
C) anapletoric reactions replenish intermediates
-ensure a net production of oaa even if degradative pathways not occurring
-produce 4 carbon intermediates by carboxylation of 3 carbon compoudns
1. Pyruvate carboxylase
pyruvate + HCO3- + ATP --.> OAA + ADP + Pi + H+
-laso in glucogenesis
-uses bitoin as cofactor, creates similar amide linkage like lipoic acid to have
flexible arm
-acetyl coA is postive effector—if there is extra acetyl coA then more OAA needs
to be produced
2. PEP carbocykinase, PEP carboxylase and malic enzyme
-also employ biotoin to activate Co2 and carry it to acceptors
16.3 TCA Cycle Regulation
-flow of carbons uder reulation at two levels
A) PDH complex regulated by allosteric and covalent mechanism
1. inhibited by ATP, acetyl CoA and NADH, long fatty acids
-turned off hwne ample fuel available in form of fatty acids and acetyl coa
-ATP/AMP and NADH/NAD ratios hgihg
2. covalent protein modifiation
-E1 reuglated by reversible phsop catalyzed by pyruvate dehy kinase
-phos form is inactive, desphosphorlated form is actice
-pyr dehydro kinase is stimulated by NADH, acetyl Coa and inhibited by
pyruvate, Ca, K, and ADP
- phosphatates removes phosphoyrl group by hydrolysis and is stimulated
by Ca2+
**ca stimulates glycogen breakdown, making glucose aailabe for metablism
-also triggers muscles contraction, which requires ATP hydrolsys, so it make
sense for it to stimulate metabolism of glucose to produce ATP
B) CAC regulated at 3 exergonic steps
1) citrate synthase
 -stimulated by ADP, inhibited by ATP NADH citrate, succinyl coa
-reulated by substarte availaibty- less substrate inhibits
2) isocitrate dehydrogenase
positive effectors- ADP, NAD, Ca2+ negative: ATP, NADH
-reversible phos can inhibit binding of isocitrate
3) a ketoglutarate dehy complex
postive=Ca2+ negative= ATP, NADH, succinly CoA
--overall rate controlled b rate of conversion of pyruvate to acetyl Coa and by flux through
citrate synthase, isocite dehy and a keto dehy
-laregly determined by concentrations of substrates/product
-end products ATP and NADH inhibitory
substrates NAD nd ADp are stimulatory
production of acetyl Coa insihibed by metablosites tha have a lot of metabolic energy
(ATP, acetyl Coa, NADH, and fatty acid) and stimulated by metabolies that indicate reduced
energy supply (AMP, NAD, CoA

Carbon tracing
-pyruvate-
COO- this is carbon 4 and carbon 3
Middle C is carbon 2 and and carbon 5
CH3 group is carbon 6 and 1

Chapter 19: Oxidative Phosphorylation-synthesis of ATP from ADP coupled to electron transfer
from a substrate to molecular oxygen

19.1 Electron transfer reactions in mitochondria

- Mitochondria structure
A. outer membrane- freely permeable to small molecules ions
B. inner membrane- impermeable to small molecules/ions, need transporter to cross
Contains: respiratory electron carriers (complex I-IV), ATP synthase
C. Matrix: contains: pyruvate dehy complex, ctiric acid cycle, fatty acid/AA oxidation
enzymes, DNA ribosomes, ATP (transferred in), ADP/pi (tras out), Mg, Ca, K
- Electron Transport: Redox Centers
A. Flavin Mononucleotide (FMN) – tightly bound prosthetic group of flavoproteins
-can accept one or 2 electrons in form of hydrogen atoms (FMNH, FMNH2)
B. Heme (component of cytochrome)- iron containing protsethic group (cytochrome a,
b,c), cychromes are integral proteins, only transfer one electron
C. iron sulfur clusters (fe-s, 2fe-2s, 4fe-2s) sulfur ceoms from cysteine or inorganic, one-
eletron trasner where one iron is oxidized or reduced
D. copper ion cu2+ + e-  cu+
E. ubiquinone (coenzyme Q, or Q) hydrophobic quinone, freely diffisuble in inner
mitochondrial membrane. Accepts one electron- QH semiquinone radical, or two
QH2 to from ubiquinol (accepts electron with proton)
- Electron Transport: Reaction Sequence
-
- Electron Transport: Complexes
 A. Complex I: NADH-Coenzyme Q Reductase/ NADH dehydrogenase
-NADH + 5Hn +Q  NAD+ + QH2 + 4Hp
-hydride ion and proton transferred to ubiquinone coupled to 4 protons transferred
to intermembrane space; ubiquinol diffuses to complex III
-coenzymes: FMN, Fe-S clusters
B. Complex II: Succinate-CoQ reductase / Succinate dehydrogenase
-succinate + Q  fumarate + QH2
-coenzymes: FAD, Fe-S clusters
C. Complex III: CoQ-Cytochrome c reductase, cytochromb1c complex
-QH2 + 2 cyt c1 (oxi) + 2Hn  Q + 2 cyt c1 (red) + 4Hp
-coenzymes: cyt b complex, Fe- S complex, cyt c1
-cyt c (soluble protein of IM space) accepts electron and moves to complex IV
-each QH2 donates one electron to cyt c and one electron to Q on N side, releasee
2 protons per Q molecule into intermembrane space
-uses 2 protons per Q, taken from matrix
-path of electrons described by Q cycle
Stage 1: QH2 + Q + cty c1 (oxi)  Q- (radical) + Q + 2Hp + cyt c1 (red)
Stage 2: QH2 + Q-(rad) + cyt c1 (oxi)  QH2 +2Hp + Q + cyt c1 (red)
-cyt b pass electrons from QH2 to Q
D. Complex IV: Cytochrom c oxidase- carries electrons from cyt c to o2 , red to H2O
- 4 cytc (red) + 8Hn + O2  4 cyt c (oxi) + 4Hp +2H20
-electron transfer: cyt c -> CuA  cyt a  CuB  cytA3  02
-redox cetneres carry only one electron at a time, 4 protons pumped into IM space
-coenzymes: cyt a, cyt a3, cu ions
Summary of electron transport
-electrons reach Q through complexes I and II and reduce to QH2
-QH2 passes electrongs to Complex III which passes to cytochrome c
-Complex IV transfers electroms from reduced cytochrome c to O2
-Complex I and III transfer 4 protons to IM space, IV does II
- NADH + 11Hn + 1/2O2  NAD+ + 10Hp +H20
-chemical potenial energy- ∆ pH = 0.75-0.80
-electrical component-∆ ψ =0.18 (0.15-0.2)
electrochemical potential (membrane potential)
G=2.3RT(∆ pH) + F(∆ ψ ) = 2.3(0.0083)(298)(.8) + (96.5)(0.18) = 21.9
FOR NET OXIDATION OF NADH
G= -2(96494C/MOL)(0.001 KJ/J)(1.136) = -219 KJ/MOL (transfer of 2 e- and 2
protons)
19.2 ATP Synthesis
-protons flow f=passivel back into matriz through pore which drives synthesis of ATP
-catalyzes formation of ATp from ADP and Pi accompanied by flow of protons from P to
the N side of the membrane
A) ATP synthase has two functional domains, F0 and F1
-also called complex V
F0 intergral membrane protein, has proton pore protons leak through
F1 is a peripheral membrane protein
B) ATP is stablizlied relative to ADP on the surface of F1
 - ATP synthesis is eradilly reversible , with G near 0
-ATP binds ATP more tightly, releases enough energy to counterbalance cost of making
ATP ( f0f1 bind ATP with very high affinity and ADP very low
C) Proton gradient drives release of ATP from enzyme surface
-enzyme must cycle btwn for that binds ATP tightly and oen that releases
-each B usbunit has 3 different conformations, and has one catalytic site for ATP
synthesis
-F1 has 9 subunits with comp of a3B3ydE
-domain y associates primarily with one b subunit, called b empty
-conformations differ, partly becuaseoof ssociation of y subunit, which extend to
difference in ATP bidning sites
-3 conformations-B-ATP (tight), B-ADP (loose), B-empty (open)
-f0 has 1 c subunits arranged in circle
D) rotational catalysis is key to biding change mechanism
-three active sites of F1 take turns catalyzing ATP synthesis
-sates in ADp conf, which binds ADp nd Pi
-changes conformation to B-ATP form that stabilizes ATP
-changes conformation to B-empty which has low affinity for TP and new TP leaves
enzyme surface
-conformation changes driven b passage of protons though F0 pore, which causes cyliner
of c subnits to rate around axis
-with each rotation of 120, y comes into contact with difernet b subunit which forces it
into b empty
-rotates in one direction when synthezising atp and the other directio during hydrolysis
E)Proton motive force energizes active transport
-provide energy for transporting substates ADP and Pi into and product ATP out of
mitochondrial mari
1) adenine nucleotide translocase is antiporter- the same protein moves ADP into matriz
and ATP out
-binds ADP3- and transports it to matrix in exchange
-activity favored by elecochemical gradient- because matrix has overall negative
charge ad its taking out one negativ charge drive ATP ADP exhange
2) phosphate trasnlocase promotes sympot for one H2Po4- and one H+ into matriz
-favored by proton gradient
-requires movement of one proton from P to N side of inner membrane,
consuming some of energy of electron transfer

F) Electron Shuttle Systems

Glycerophosphate shuttle (skeletal muscle and brain NADH shuttle)
dihydroxyacetone phosphate accepts 2e from NADH to become glycerol -3-
phosphate, who then transfers 2e- to FAD on the inner membrane, who transfers
electrons to ubiquinone and thus into complex III
-only gets 1.5 ATP per pair of electrons
-doesn’t involve membrane transport systems
malate-aspartate shuttle (liver, kidney and heart NADH shuttle)
NADH in cytosol passes 2 e’ to OAA, producing malate
 OAA + NADH + H+  malate + NAD+ (cytosolic malate dehydrogenase)

Summary of electron transport coupled to oxidative phosphoryltion

A) Spontaneous reactions of elctron transport (gibbs free energy)
which equals -219kj/mol
B) Protons pumped out of mitochondrial matriz (work)
C) Proton gradient (potential energy)- made up of chemical
component (delta ph) and electrical component (delta v)
D) Electrochemical potential (membrane) = 21.9 kj/mol of H
E) Proton motive force
F) Spontaneous flux of H+ into matrix via atp synthase (kinetic e)
G) Roration of c assembly and y subunit (work)
H) Sequential and coordinated confromatioanl changes of active sties
of 3 ab dimmers of atp synthatse
I) ADp+ Pi  ATP (chemical energy

Summary of glucose catabolism reguation

1) hexokinase
intermediates: glucose  glucose 6 phosphate
effectors: += Pi negative: G6P

2) phophofructokinase: F6P F1,6bisP

effectors: positive- F2,6bisP, Pi, AMP/ADP, NH4+ negative- ATP, citrate, H+
-also regulated by F6P availibity

3) pyruvate kinase: PEP pyruvate

effectors: positive- ADP/AMP, F 16 bisP or F2,6bisP
negative- ATP, acetyl COa, alanine, NADH, fatty acids
other regu- liver isozyme: dephospohrylation, Phosphorylation stimulated by low glucose

4) PDH complex: pyruvate  acetyl-COA

positive effectors: ADP, AMP, Ca
negative: NADH, Acetyl-CoA, ATP
other: dephosph of Efi stimulated by insulin and Ca- activates
phoso of E1 stimulated by NADH, Acetyl COa, inhitbied by pyruva

5) citrate synthatse: OAA + acetyl CoA  citrate

positive- ADP
negative citrate, NADH, succinly coa, atp
also regulated by substrate availibity

6)isocitrate dehydrogenase: isocitrate  oxalosuccinate  AKGlutarate

positive- Ca2+, NAD, ADP
negative ATP, NADH
in e coli phospolrylation ihibits bhinid og isocitrat
7) a ketogluatrae deh complex : AKGlutarte  succinyl CoA
positive- Ca2+
negative- ATP, NADH, succinyl CoA

8) cytochrome c oxidase- cytochrome c 2+ availtibity

9) ATP synthatse-
ADP and Pi availability

Common cofactors:
Biotoin- CO2 carrier
CoA- acyl carrier
Lipoamide acyl carrier
CoQ, Hemes, Iron sulfur clusters- electron carriers
Integrated Picture:
Living systems always fighting entropy, which requires constant supply of energy
Metabolic pathways must stay far from equilbirum
I. 4 major classes of macromolecules
II. Biolocigcal reactions
-catalyzed by only 6 major classes
III. Metabloism
A. integrated system
1. interconnected network of rxn pathways
a. complex but oranizied
-speficiif functional compounds serve as precursors to other
compounds )glu is precuros to gln, pro, arg and purine
b. common patterns
1) energy extracted from bio compounds via oxidative degration
2) common currencies of energy transduction
a)NAD+/NADH
b)FAD+/FADH2
-NAD/FAD reduced in catabolic reactions by acceptingng
electrons and reoxidized in electron chain
c) ADP.ATP: phophoryl transfer potentical
ATP synthesis accomplished by
- Coupling to spontaneous reactions
- Thiol ester hydrolis
- Transfer of phosphate from metabolic itermediate
with high phosphoryl transfer potential (substrae
level phophorylation)
- Oxidative Phos via ATP synthase
c. coordinately nds to levels of products, substrates
1) reulation enables pathway to be sensitive to needs of cll
2) regulated enzyme actibity responds to levels of pathway
products, precuros and substates via feedback inhibtion,
allosteric substrate avail
3) multienzyme complexes channel intermediates directl to next e
nzyme of pathy, elimiate reliane on diffusion and allow
enhanced coordinate regulation
4) regulation of key (highly spontaneous) rxn control pathway
5) most pathways regulated by energy charge (ratio of adneylates)
-energy charge stays at steady state