Nobel Prizes 1907 Eduard Buchner, cell

Nobel Prizes 1907 Eduard Buchner, cell-free fermentation chem.1915 Richard M. Willstätter, researches on plant pigments, esp. chl.1918 Fritz Haber, synthesis of ammonia from its elements, chem.1922 Archibald Vivian Hill, production of heat/lactic in
muscle;1923 Frederick Grant Banting , discovery of insulin.1929 Arthur Harder, fermentation of sugar and fermentative enzymes.1931 Otto Heinrich Warburg , discovery of respiratory enzyme action.1953 Hans Krebs, the TCA cycle, phy.1964 Dorothy
Hodgkin, determinations by X-ray tech of the structures of important biochemical substances, VB12, chem.1964 Konrad Bloch mechanism and regulation of cholesterol and fatty acid metabolism, phy.1970 Luis F. Leloir, discovery of sugar nucleotides
and their role in the biosynthesis of carbohydrates, chem.1977 Rosalyn Yalow, peptide hormone production in brain and radioimmunoassay.1978 Peter D. Mitchell , understanding of biological energy transfer and the chemiosmeric theory, chem.1985
Michael S. Brown , regulation of cholesterol metabolism, phy.1988 Johann Deisenhofer , determination of 3D structure of photosynthetic reaction center.1992
Edmond Fischer , reversible protein phosphorylation. 1997 Paul D. Boyer , elucidation of
enzymatic mechanism in synthesis of ATP.
Chapter15 Glycolysis(in cytosol,net 2ATP,preparatory and payoff phase):Cys residue(-S) involved in Glrhyde3PP dehyase,followed by phosphorolysis;Ppglycerate mutase:Ppryl carried by Hisresidue(3PPGlyrate23BPPglyrate2Ppglyrate)|Pyru's
fates:A-CoA/methanol +CO2/lactate|Multienzyme complexes:substrate channeling(dilution dissociation)|Glycg breakdownGlc1PP(Glycg PPlase+(bifunc)debranching enz:3/1time(tranferase act)+(a16glycosidase
act))Glc6PGlycolysis|Digestion of sugar:Salivary a-amylase(starch/Glycg Oligosac);pancreatic a-amylase(maltoses,dextrins);maltase,dextrinase,lactase,sucrase,trehalase(monosac);lactose intolerance sundrome(lactase)|Pentose PP
pathway:2NADPH generated;regenerating 6C|Glcg PPlase:a(active,Pplated at Ser,inacted by glc binding dePPlation)b(inact,dePPlated,partially activated by AMP);Ca2+ Kinase,ba|Control over Glycolysis:mianly PFK-1(irreversible reactionglc
away from PentosePP,other factors seen in map), partially by hexokinase(controlled by blood Glc level and inhited by F6P) and pyruvate kinase(ATP,A-CoA,long-chain FAs inhit isozymes of pyruvate kinase).
5 Coenz(Coenz A(CoA-SHdelivers activated acyl
Chapter16 Citric Acid Cycle:3 stag es:A-CoA syn(pyru,mt matrix)A-CoA oxidation(mt matrix)e transfer,oxidative PPlation(mt mem)|PyruA-CoA(oxidative decarboxylation of pyruvate):
groups),(Lipoateelectron,acyl carriers, swings between three different active sites of the PDComplex),TPP,FAD,NAD+);3 enz(E1: PDH, E2: Dihydrolipoyl transacetylase, E3: Dihydrolipoyl dehydrogenase)|Pathway:8 steps:1.A-CoAcitrate( Hydrolysis
of the thioester bondmuch energy;citrate synthase conformational change binding with
oxalo;the only SLP in cycle:succinyl-CoA synthetase(his residue in map);succinate dehynase(A flavoprotein with FAD,3 Fe-S centers;only integral mem pro for
CAC, Malonate(丙二酸) is a strong competitive inhibitor)Fumarase:trans and L specific)(not maleate and D-malate)|multi-enzyme complex in CAC|Intermediate Replenishment:1. Pyru carboxylase(biotin as carrier activated 1C unit and between two active
sites):Pyruvate +HCO3+ATP oxaloacetate +ADP +Pi 2. PEP carboxylase: PEP+CO2 +GDP Oxalo+GTP 3.(PEP carboxylase) PEP+HCO3Ox+ Pi 4.malic enz:Pyruvate+HCO3+NAD(P)Hmalate+NAD(P)+| anaerobic micros use incomplete
CAC(lack a-ketoglutarate DH) for syning precursors,so do plant peroxisome and glyoxy-somes|CAC regulation:3 enzymes:seen map|Only through glyoxylate cycle:net conversion acetatecarbohydrates,no release of CO2 |
Chapter17 FA Oxidation: Biological functions of lipids:•Stored energy•Cell membrane•Pigment (ex. Retinal, Vit A etc.)•Cofactor•Transporter (ex. dolichols)•Hormones•Extracellular and intracellular messengers•Anchors for membrane
proteins|Triglycerol (TG,highly reduced, anhy drous and chemically inert)FAs|Chylomicron: lipid-binding proteins in the blood,transport of TGs,phospholipids,cholesterol,cholesteryl esters between organs| Mobilization of TGs: •Release of FAs from TGs
(lipolysis)•Controlled by hormones:Feeding:glucose down, insulin up, and FAs stored as TGs;Fasting: Insulin down,lypolysis occur, further stimulated when epinephrine up| Perilipin:family of proteins on surface of lipid droplet,restrict access, prevent
untimely lipid mobilization.|GlycerolGlyrhyde3P:(glycerol kinase)L-glycerol 3 P(glycerol 3-P DH)Dihydroxyacetone P(triose P isomerase)D-Glyceraldehyde 3-P,95% energyFA|C ωH3-(CH2)nCbH2-CaH2COOH|FA enter mt by acylcarnitine/carnitine transport(Carnitine palmitoyl transferase, links 2 different pools of CoA,of mt and of cyt)|Palmitoyl-CoA + 7FAD + 7CoA  8 acetyl-CoA + 7FADH2 + 7NADH +7H+ |Odd number FA:propionyl-CoAsuccinyl-CoA via 3 steps(seen map
left of mt)|belta-Oxidation enzs bind together for G- bac,dissociated for G+| Mitochondrial very-long-chain-specific system:TFP (trifunctional protein,a4b4): Enz2 & Enz3 (a subunit), Enz4 (b subunit);Peroxisomes (animal):MFP (multifunctional
protein):MFP1: Enz2 & Enz3 & delta3.2 -enoyl-CoA isomerase,MFP2: Enz2 & Enz5 (D-3-hydroxyacyl-CoA dehydrogenase) Glyoxysomes (plant):MFP, Enz2 & Enz3 & delta3.2 -enoyl-CoA isomerase & D-3-hydroxyacyl-CoA dehydrogenase ( or
epimerase )|FAA-CoAglc(animal:even number,no;odd,yes;plants:yes,glyoxylate cycle)|omega Oxidation in ER|Phytanic acid oxidation in Peroxisome| Difference between phytanic acid and pristanic acid: methyl group on beta carbon cannot undergo
b oxidation|Ketone body: Acetyl-CoA CoA in liver can be converted to keton bodies for exporting to other tissues in conditions of starvation and uncontrolled diabetes|,back toA-CoA in extrahepatic tissues| Regulation:Shortterm regulation(substrate
availability; allosteric effectors and/or enzyme,eg: Acetyl-CoA carboxylase (ACC), Carnitine acyltransferase I (inhibited by malonyl-CoA)); long-term regulation:(regulation of the rate of enzyme synthesis and turn-over)e.g. regulated by hormones (insulin,
glucagon)|Diseases:carnitine deficiency: inability to transport fatty acids into the mitochondria;CPT I/II deficiency;Deficiency in A-CoA DH,following fasting; Refsum disease:defect in phytanoyl-CoA hydroxylase, high blood level of phytanic acid and
severe neurological problems(blindness and deafness); Zellweger syndrome are unable to make peroxisomes and therefore lack all the metabolism unique to that organelle|
Chapter 18 AA Oxidation:major in liver.Sources of AAs for degradation:defective/un-neededcellular protein,in lysosomes (no ubiquitin modification, no ATP needed) or proteasomes (ubiquitin-modified and ATP-requiring specifically target the proteins
that need to be degraded)| Ubiquitin:small, heat steady,76AAs,only in eu, highly conserved,mark protein for desteuction, E1: ubiquitin activating enzyme,E2: ubiquitin-conjugating enzyme,E3: ubiquitin-protein ligase(in concert;recognition)|Exces
AAcannot be stored,to Pyru/A-CoA;fasting glc/ketone bodies;FAs, stored as TGs in adipose tissue|Excretory Forms of nitrogen:aquatic ammonium; terrestrial vertebrates urea;birds,reptilesuric acid|transamination:a-ketogularate+L-aaLglutamate+a-keto acid (amino-transferase)|free ammonium added to GluGln,then transported to liver,Gln can function as source of amine in biosyn.|Glc-Ala cycle between muscle and liver:Glc in musclepyru+Gluala+aketoglutarateliverpyruGlc; Alanine brings both carbon and nitrogen from muscle|PLP:cofactor of aminotransferase,temporary amino carrier, bound to the enzyme active site through an aldimine 亚胺醛 linkage to the ε-amino group of Lys residue,
reversible transformation between aldehyde form and aminated|Reactions at C-alpha(also the multiple roles of PLP, protonated form acts as e- sink to stabilize catalytic intermediates that are negatively charged): racemization 外消旋; decarboxylation
and transamination;Reaction at C-beta:trp synthetase;Reaction at C-gama:cytathionine beta-synthase| Transamination occurs via a Ping Pong mechanism: The incoming AA binds (I substrate) to the active site, amino group to PLP, leave a-keto acid (I
product); The incoming a-keto acid (II substate) then binds, accepts the amino group from PMP, and departs an amino acid (II product).|Urea Cycle:liver:NH4+urea;Carbamoyl PP syn:2ATP needed:1 to acti HCO3-,1 to PPate carbamate 氨基甲酸盐; Urea
Cycle linked to TCA: Aspartate argininosuccinate shunt of CAC:oxalo+Glu2-ketoglutarate+asp;asp deaminated to fumarateTCAOxalo:1.TCA,2.PEPGlcNG,3.PEPPyru; Fumarate is converted back to Asp via a partial usage of the citric
acid cycle; UC Regu- lation:1.allosteric:N-acetyl-glu (syned as glu up),see map;2.Gene:Starvation/high Protein intakeUC enz↑|AAs Degradation:keto acids converted to 7 metabolites before TCA:A-CoA,fumarate,a-keto glutarate,succinyl
CoA,oxalo,acetoacetyl-CoA,pyru;1C carrier:biotin:most oxidized,H4 folate:intermediate,adoMet(S-腺苷甲硫氨酸):reduced;methionine 甲硫氨酸:actiedS-adeno-sylmethionine;To acetyl-CoA:via pyru: Ala, Cys,Gly,Ser,Threonine,Trp;via acetoacetylcoa: leu,
lysine,phy,trp,tyrosine; Alanine: to pyruvate directly by transamination;Tryptophan: cleaved to ala as one part;Thr: cleaved to acetyl-CoA + glycine (10-30% of threonine catabolism, major pathwa in humans lead to succinyl-CoA)
Glycine:(1)serine;(2)CO2 + NH4+;(3) glyoxylateoxylate; Serine:serine dehydratase (remove a-NH2 and b-OH in a single PLPdependent reaction),Cysteine: via two steps (remove sulfur atom and transamination); Intermediates of trp catabolism are used as for biosyn: .nicotinate, indoleacetate, and
serotonin ;Phenylketonuria(PKU):phy hydroxylase (mixed function oxidase, tetrahydrobiopterinn as cofactor, carries e from NADH to O2,oxidized to dihyrobiopterin, reduced by dihydrobiopterin
reductase in a reaction that requires NADH.;phy phenylacetate +phenyllactate;Alkaptonuria: Dr. Archibald Garrod made connection between human disease and an enzyme,homogentisate excretaed and black; Leu, Ile, and Val deaminated and
decarboxylated by branched-chain aminotransferase and branched-chain a -keto acid dehydrogenase complex(deficiencymaple syrup ureine disease ); Methylmalonic academia(MMA accumulationvaline and isoleucine):methylmalonyl-CoA mutase;
Chapter19 PPlation:e carriers:FMN:1;FAD:2;Fe-S(>8):I,II,III;heme:III(cytb,c1),IV(cyta,a3);Reduced cyt 3 bands; Ubiquinone (or coenzyme Q):only e carrier not bound to a protein, diffuse freely in the lipid bilayer,QQH2(ubiquinol);NADH
DH(2e4H)flavoproteincyt bc1(2e4H)cyt C oxidase(3Cu2hemeA,O2 reduced,2e2H),increasing standard reduction potential,studies with inhibitors also,oxidation kinetics:earlier oxidized,nearer to end,ion-exchange chromatography;Obligatory
Couple:AtP syn by proton motive force(release ATP from ATP synthase,ATP much higher affinity to enz than ADP):chemical(delta pH) and electrical potential(delta phi);supported by:enclosed mem needed, weak hydrophobic acid uncouple,carry
protons;artificiall H+ gradient for ATP syn;unifies energy transduction with PPlation.ATP synthase:F0:ab2c10-14,channel;F1: α3β3γδε,synthase;binding-change mechanism:supported by crystallography and actinfilament,3 beta conformations:-ATP,-ADP,empty;10-14H+/3ATP formed; the proton gradient drives the rotation of the c ring using two half-channels on the a subunit,and protonation/deprotonation of an Asp essential for rotating the c ring and the gama subunit;H+ gradient do other work:flagella
movement,active transport through inner mem of mt(ATP,ADP,H2PO4),generate heat(brown fat,thermogenin, uncoupling pro); NADH shuttle:malate-asp shuttle system(liver,kidney,heart,oxalo+NADHNAD++malatevia malate-a-ketoglutarate
transporter,mt matrixoxaloasp via glu-asp transporter;glycerol3P shuttle:glycerol3P(glycerol3P DHQ)dihydroxyacetone P|Regulation:acceptor control(rate of respiration generally controlled by the availability of ADP),by the relative levels of ATP,
NADH, ADP, AMP, Pi, and NAD+;Complexes I, III, and IV and ATP synthase are assembled by using subunits made in both the cytosol and mitochondria|PhotoPPlation: thylakoid mem;3 steps:light capture,e flow,H pumping+ATP syn;chlorophyll(a,b,Mg
needed);exciton transferreaction centerchemical energy via charge separateion; PSII and PSI in tandem move electrons from H2O to NADP+ and to produce a transmembrane H+ gradient; red light render cyt reduced and far-red
opposite;P680+(PSII) extract e from water,producing O2,via Mn-containing Oxygen evolving complex; Protons are pumped stroma the thylakoid lumen by Cyt b6f complex; About 3ATP/O2 produced,4 photons(with e transferred); Cyclic e flow in PSI
produces ATP, but not NADPH and O2(Fdcyt b6f complex);
Chapter20 Gluconeogenesis:major precursor: lactate,pyruvate,glycerol,3-phosphoglycerate|central:pyruvateglc|3 same with glycolysis|highly conserved|3 bypass,1pyruPEP:pyruoxalo,then 2ways:1.malatecytoxaloPEP;2.PEP(mt matrix
by mitochondrial PEP carboxykinase isozyme)cyt; 2.F1.6BPF6P:by F1.6Bpase,not FPK-1 mg2+dependent;3.Glc6pGlc:by Glc6Pase,ER lumen liver kidney;|6 high-energy P required/glycolysis 2ATP|sources of NADH: lactate dehydrogenation in cytl
or malate of mt mx(at pyruPEP)|Most Aas not FAs(lys,leu,even FAs) glucogenic in mammals,plants,bact do|FA oxidation give energy for GLcNG|Futile cycle:ATP consumed for heat|Regulation:A-coA:inh pyr dehyd cplex(glycolysis),stimu pyruvate
carboxylase (of gluconeogenesis);AMP,F26BP:inh FBPase-1,sti PFK1,citrate inverse|PFK-2/FBPase-2,bifunc|Glucagon:stimu phosphorylation of PFK-2/FBPase-2,inh formerinh glyco|Fas,AAssucrose(seeds): 4steps:β-oxidation,glyoxylate cycle
(glyoxy-some),CAC(mt),GlcNG(cyt)|SUGAR POLY:Glc1P+UTPUDP-Glc (UDP-glc PyroPPlase)|Glycg synthase:UDP-Glcnonreduca14glycosidic; branch(a16): glycosyl-(4→6)-transferase;1st glc:Tyr194 glycogenin; Glycg synase(a/b) and glycg
Pplase(a/b),both a active:epinephrine(muscle)/Glcgon(liver)PKAPplationlatterformer |ADP-Glcstarch/bac glycg,syn of ADP-glc limiting|SucroseUDP-Glc+Fru6P cytosol plant(suc6P synthase,then suc6p phosphatase)| Galactosyltransferase+alactalbuminlactose synase;Galactose from UDP-Glctose+D-glucoseD-lactose|UDP-GlcGlucuronate(dehy),L-ascorbic acid(D-glucuronate L-gulonateL-gulonolactone) scurvy|CO2 fix:fix,reduc(3ppgrate13bppgrate(kinase)
glrhyde3ppate(dehydr),1NADP+1ATP used),regene(2aldolase2transketolase TPP temp carrier 2C:glrhyde3ppate's 3 fates:1glc1Pstarch syn(chlp stroma);2,3cyt(Pi-triosePP antiporter) 2sucrose syn,3glycolysis|2NADPH3ATP for 1CO2 fixation|
Pi-triose PP antiporter's 2 roles:1.transport materials:triose PP:stromacyt,Pi reverse;2.energy:ATP,NADH/NADPH:stromacyt|Rubisco regu :Carboxylation of Lys-191 large by CO2carbamate ,Rubisco activase(low),Mg2-carboxyarabinitol
1P,transition-state analog|Light:1.stroma pH,Mg↑F16BPPtase;2.redu S-S: glrhydes 3P deHgenase,F16BPPtase,sedoheptulose-1.7-BPPtase,ribulose-5-PP K|PhotoPPrylation,CO2 fixation,sucrose/starch syn,and
glycolysisregulation:DARK:GlcNG↓,Glyco↑F26BPP:
light:3CPFK2 F26BPP↓FBPase1(GlcNG);dark:PiPFK2F26BPP ↑PFK1(glyco);suc6P synaseGlc6P(light) andPi(dark);ADP-Glc
pyroPPlase3PPGlycerate, Pi| Photorespiration:3Ppglycerate,and( glycolate paway)phosphoglycolate|C4 pathway:PEP+CO2Oxalo(PEP caboxylase,mesophyll)malatebundle-sheathpyru(malic enz)(back to PEP in meso by Pyru PPdiK)
Calvin;OVERALL:5ATP for 1CO2;
Chapter21 lipid synthesis:A-CoA via carboxylationmalonyl-CoA,both from A-ACP and N-ACP(Acetyl-CoA-ACP transacylase);acetyl shuttle through mt inner: oxalo+A-CoAATP-citrate lyasecitrate+CoA-Sh via citrate transporteroxalomalate(via
malate-a-ketoglutarate transporter) or furtherpyru via pyru trans); TCA, subcellular compartmentalization, and PentosePP provide the carbon and reducing power, glycolysis and oxidative PPlation provide the ATP for fatty acid synthesis;NADPH(in
adipocyte from oxidative decarboxylation of malate by malic enzyme, NADP++ NADH + ATP +H2O NADPH + NAD++ ADP + Pi+ H+(by malate DH, malic enzyme and pyruvate carboxylase;in hepatocyteand mammary gland:PentosePP;in chlp stroma
from light reaction)|A-CoA carboxylase:in bac,3 units: biotin carboxylase, biotin carrier protein, and Transcarboxylase,in animal,of a single peptide(pingpong mechanism,2 sites);FAS structure:bac,plant:7 units;yeast:2 units,each
6;animal:singledimer;Comparison between beta-oxidation and syn(in map);regu of A-CoA carboxylase(key regulatory step): allosteric regulation+hormone-dependent covalent modification(active when dePPfilament,citrate
activate.ATP,glucagons,epinepherine inh, insulin,AMP sti);FA oxidation blocked during syn:Malonyl-CoA inhi carnitine acyltransferase I, block the beta-oxidation of FA in mt; NADH inhi 3-hydroxyacyl-CoA DH; acetyl-CoA inhibits thiolase;Fa syn in chlp
stroma in plant,while acoa carboxylase not activated by Pplation, but high pH and Mg;Elongation of FA:SER mem:similar to FA syn,Coa as acyl carrier;in mt: Enoyl-CoA reductase: use NADPH; Acyl-CoA dehydrogenase:use FAD;only in
plants:oleate,on phosphatidylcholine;Desaturation of FA: fatty acyl-CoA desaturase(mixed function oxidese), together with cytochrome b5 and cytochrome b5 reductase;Cyclooxygenase (COX),called prostaglandin H2 synthase (bifunctional
enzyme):cyclooxygenase activity and peroxidase activity, Eicosanoids from arachidonate by the action of cyclooxygenases and peroxidases;Palmitate as major produce of FA syn;| Biosynthesis of triacyloglycerols:TG and
stimulate,inhibit
glycerophopholipidphosphatidic acid;
E.coli :phosphatidylethanolamine,phosphatidylglycerol,cardiolipin (diphosphatidylglycerol);Glycerophospholipids in
Glycerophospholipids in
eukaryotes:(biosynthesis:ER and Golgi complex) phosphatidylethanolamin(脑磷脂)Phosphatidylcholine (lecithin, 卵磷脂),phosphatidylinositol|cholesterol syn:liver,Cacoa, 1.Stage I is the synthesis of isopentenyl pyrophosphate,activated isoprene unit,key
building block of cholesterol.2. Stage II is the condensation of 6 isopentenyl pyrophosphate to form squalene.3. In stage III, squalene cyclizes in an astounding reaction and the tetracyclic product is subsequently converted into cholesterol. 1.Mevalonate is
converted in the cytosol to isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DPP).2. IPP and DPP form farnesyl pyrophosphate in the cytosol.DPP + IPP <=> Geranyl Pyrophosphate + Ppi,Geranyl Pyrophosphate + IPP <=> Farnesyl
Pyrophosphate + Ppi 3. Farnesyl pyrophosphate is then converted to presqualene pyrophosphate in the membrane of ER.2 Farnesyl Pyrophosphate <=> Presqualene Pyrophosphate + Ppi 4. Presqualene pyrophosphate is subsequently converted to
squalene, also in the membrane of ER. 5. Squalene is cyclized there to lanosterol, which is subsequently converted to cholesterol; Regulation of HMG-CoA Reductase as rate-limiting step, it is the principal site of regulation in cholesterol
synthesis.1.Phosphorylation by cAMP dependent kinase inactivates the reductase 2. Half-life of HMG-CoA reductase is 3 hours and depends on cholesterol level 3.Gene expression (mRNA production) is controlled by cholesterol levels.
2+
 Principles of Bioenergetics  ATP provides energy by GROUP TRANSFERS  Adenylate kinase requires Mg  Transphosphorylations between Nucleotides Occur in ALL Cell Types  INORGANIC Polyphosphate Is a Potential Phosphoryl Group Donor
 Biochemical and Chemical Equations Are NOT Identical  Biological Oxidations Often Involve DEHYDROGENATION Free-energy calculation: the STANDARD Reduction Potential  FMN contains ribulose in CHAIN form, not in circle form
 Glycolysis and the catabolism of hexose  Thiamine pyrophosphate is the coenzyme of transketolase  TPP carries the active acetaldehyde groups  The phosphofructokinase in bacteria and plants uses PPi  Aldolase: Class I: animal/plants
2+
, form Schiff base; ? Class II: bacteria/fungi, no Schiff, Zn instead  PGAld dehydrogenase: contains His and Cys residue, inhibit by Hg
Pentose phosphate pathway: transaldolase: 7+3=4+6  transketolase: 5+5=3+7; 3+6=4+5
 transaldolase/transketolase intermediate: resonance stabilization  Regulation of Glycolysis  Glycogen phosphorylase only acts on the reducing ends of glycogen, split α-1,4 bonds and produce G-1-P  The debranching enzyme (glucantransferase) first
transfers extra glucose chain to another reducing end, forms α-1,4 bond. Thencleaves the α-1,6 bond and removes the remain one glucose. In liver, the G-6-P enters ER lumen and cleaved by glucose-6-phosphatase on membrane
, forms G and Pi, add blood Gs. The source of glycogen genesis:UDP-glucose ; G6PG1P +UTP UDPG +Pi.  Amylo transglycosylase or glycosyl(4,6) transferase transfers glycogen fragments from nonreducing ends to chain middle thus made α-1,6
bonds while glycogen synthase make α-1,4 bonds during glycogensynthesis.bonds while glycogen synthase make α-1,4 bonds during glycogensynthesis. Glycogen synthase requires a primer with at least 8 Gs to initiate glycogen synthesis, which synthesized
by glycogenin(Tyr involved) Hexokinase Isozymes (I-IV) of Muscle and Liver Are Affected Differently by Their Product, Glucose-6-Phosphate. Muscle: hexokinase I, II(predominant),III : high G affinity, inhibit by G6P  Liver: hexokniase IV: low
G affinity and Km, inhibit by specific protein but not G-6-P. Phosphofructokinase-1 Is under Complex Allosteric Regulation.  Pyruvate Kinase Is Allosterically Inhibited by ATP, acetyl-CoA, ala and FAs, cAMP dependent and PKA stimulated. L form is inactive
and alsoregulated by hormones. In liver it was also inhibited by glucagons. Fructose 2,6-BPi Is a Regulator of Glycolysis and Gluconeogenesis  Insulin stimulates GLUT4, hexokinase and glycogen synthase
 The Citrate Cycle 3 steps: 1)production of acetyl-CoA; 2)acetyl-CoA oxidation;3)electron transfer and oxidative phosphorylation The electrons removed from the hydroxyethyl group derived frompyruvate pass through FAD to NAD in E3
 FeS in aconitase: 3 Cys binds to Fe and the 4 th Fe binds to the citrate  2 types of isocitrate dehydrogenase: NAD + /NADP+, includes Mn2+ Succinyl-CoA synthetase: +His residue transfers Pi to the GTP  4 anaplerotic pathways in calvin cycle: pyruvate
malate through malic enzyme; pyruvate oxaloacetate through pyruvate carboxylase; PEP to oxaloacetate through PEP carboxykinase or PEP carboxylase
 Fatty acid catabolism Intestinal lipases degrade triacylglycerols in intestinal lumen.  Fatty acids and other breakdown products are taken up by the intestinal mucosa and converted into triacylglycerols. Triacylglycerols are incorporated, with cholesterol
and apolipoproteins, into chylomicrons.  Chylomicrons move through the lymph and bloodstream to tissues.  Lipoprotein lipase, activated by apoC-II in the capillary, converts triacylglycerols to fatty acids and glycerol.  The surface of adipocytes in cell
are coated with perilipins, a family of proteins that restrict access to lipid droplets  VB12: 5'-deoxyadenosine +Corrin ring system(CO3+) ribonucleotide  Fatty acids bind to albumin for the blood transportation. Glycerol catabolism: see atlas
 Fatty acid activation: 2 ATP consumed FAs+ATPFA-AMP+PPi; FA-AMP+CoA-SHacyl-CoA+AMP  Acyl-CoA transport through mt membranes: carnitine acyltransferase; I: outer membranes; II: inner membranes  Rate-limiting step for FA oxidation:
carnitine transport speed. 3 steps. Malonyl-CoA inhibits the carnitine acyltransferase I in order to prevent simultaneous synthesis and degradation of FAs. FA oxidation has 3 steps: β-oxidation, TCA, electron transfer & oxidative phosphorylation
bound to mt membranes) has shortened the fatty acyl chain to 12 or fewer carbons, further oxidations are catalyzed by a set of four soluble enzymes in the matrix. The phosphorylation of ACC made it lost the activity to synthesize FAs. Glucagen and PKA
stimulate phosphorylation while insulin inhibits.  The β-oxidation enzymes (short-chain specified) in mt andG bacteria have 4 separate subunits; the G bacteria has one enzyme in whole; mt long-chain specified has Enz-1
+
and glyoxysomal has Enz 1/4 separated and others form
MFP.  The ω oxidation occurs in the ER
of liver and kidney, minor way, acts while β oxidation is defective.  The α oxidation deals with branched fatty acids.  Animals can convert odd-number
FAs to glucose only, while plants can both even and odd
+
 Amino acids catabolism  Pyridoxal phosphate (PLP, VB6) is the cofactor of transaminase  Glutamate release its amino group as NH4 in liver  Alanine transports ammonia from skeletal muscle to the liver
Acetyl-CoA+ Glu N-Acetylglutamate (arginine stimulates);2. N-Acetylglutamate stimulates the synthesis of carbamoyl-Pi. Each urea cycle costs 3ATP, leaves 2ADP and 1 AMP and 4 Pi  H4-folate and adoMet transfers one-carbon units.  The sulfur atom in
adoMet carries a positive charge  VB12 deficiencies can be cured by either add VB12 and also folate  Glycine degradation would lead to 3 ways: carbon to serine and produce N 5, N 10-methylene-H4-folate; by H 4-folate to CO2
 Branched-chain amino acids ( Ile,Leu,Val) are not degraded in the liver but in peripheral organs as muscles, adipose,kidney and brain.
cytb(X)antimycinAcytc 1cytc
c (CH3+CH-S-Cys)  Electron
 Oxidative phosphorylation and photophorylation Different cytochromes have different hemes. a: Heme A (CHO+pentene); b: Iron protoporphyrin IX; c: Heme
transfer NADH(X)rotenoneQ
+
+
+
+
cyt(a+a3)(X)CO,CNO 2  Electron transfer complexes Complex I : NADH to ubiquinone; NADH dehydrogenase; contains Fe-S and FMN; catalysis 1) NADH+H +QNAD +QH2, 2)NADH+5H N+QNAD +QH2+4H P Complex II: Succinate to ubiquinone; succinate
dehydrogenase; membrane bound, contains heme b and Q site, 2Fe-S, FAD. (as cytb, cytc1) Complex III : Ubiquinone to Cytochrome c; contains cytb, cytc1, 2Fe-2S, heme b H/bL/c1 , binds free cytc, QH2+2cytc1(oxidized)+2H+NQ+2cytc 1(reduced)+4H+P Complex IV
+
+
 When TFP(
: Cytochrome c to O2; cytochrome oxidase; 2CuA & 1 CuB, 2Fe-2S, heme a/a3, binds free cytc, 4 cytc (reduced) + 8H N+O24 cytc(oxidized)+4H P+2H2O. ( as cyta, cyta3) All hemes bound to cyt tightly, however, onlyheme Ccovalently bond.
 Alternative mechanism for oxidizing NADH inplant mitochondria: 2Gly+NAD+Ser+CO 2+NH3+NADH+H+  Chemical uncouplers of oxidative/photo phosphorylation:DNP and FCCP, provide dissociable H + and carry H + across the inner mt membrane and
and 234 in whole; peroxisome
dissipate the proton gradient  mt F1 ATP synthase: α3 β3 γ δ ε, β has ATP catalytic activity. mt F0 ATP synthase: a b2 c10-12  each ATP requires 4 H to formation  for every 3 ATP synthesized, 10-14 H+ required separated
malate shuttle
+
: aspartate(penetrable) +α-ketoglutarate  glutamate+oxaloacetate(later malate,penetrable),NADHNADH
liver, kidney
and heart  glycerol 3-phosphate shuttle : glycerol 3-phosphate  dihydroxy-acetone phosphate, NADHFADH 2, skeletal muscle and brain
 Heat was generated by uncoupled mitochondria in brown fats. Chlorophyll funnels the absorbed energy to reaction centers by exciton transfer  Purple bacteria: P870,PQ(II); Green sulfur bacteria: P840,Fe-S(I)  H (from H 2 O)  P680P680*
 Activity
of urea cycle is regulated on 2 levels. 1.
Pheo PQA(plastoquinone)PQB(2 ndquinine) cyt b6f  Plastocyanin P700 P700* A 0(electron acceptor chl) A 1 (phylloquinone) Fe-S Fd + Fd:NADP +oxidoreductase NADP +  Light Harvesting Complex
( LHC): chl a+chl b+ lutein
+
+
+
+
+
+
 2H 2O+2NADP + ~3ADP+8 H O 2+2NADPH+ ~3ATP+2H , PS II : 4 P680+4H +2PQB+4H 4P680 +2PQBH2, has 4 Mn2+ PS I : 2Fd(red)+2H ++NADP+2Fd(ox) +NADPH +H + ,produce reduced ferredoxin.  Concerning PSI requires less energy
glyoxylate
oxalate.
Fe-S,and
cytf,finally
than PSII, in order to prevent exciton larceny, the PSI and PSII were separated spatially. The PSII located in the stack of thylakoids while PSI facing out.  Cyt b6f complex links PSII to PSI, contains b-type cyt and 2 hemes (b H/b;L)toRieske
pumps
H+
thylakoid lumenPlastocyanin was free in chloroplasts as cytc in mitochondrial In P680, the Mn2+ binds to Tyr has 5 oxidative status.  Red drop chloroplast efficiency drop when over 680nm Red2+lights made chloroplast reduced and far-red madeit oxi.
Carbohydrate synthesis  Fixation of CO 2 has 3 stages: fixation; reduction; regeneration of acceptor  Rubisco activase: dissociate RuBP from the Lys residues of rubisco , Lys interacts with carbomoyl and Mg thus activate it. 3-PGA1,3-DPGA: 3-PGA kinase,
requires ATP  1,3-DPGAPGAld: 3-PGA degydrogenase, requires NADPH  PGAlddihydroxyacetone phosphate:triose phosphate isomerase  PGAld+Dihydroxyacetone phosphate F1,6BP: transaldolase  F1,6BPF6P: F1,6 bisphosphatase ( FBPase-1)
 F6P starch (ct matrix)/sucrose(cytosol) Each triose phosphate from CO 2 requires 6 NADPH and 9 ATP, meantime, each glucose requires 12 NADPH and 18 ATP Glycogen synthase and glycogen phosphorylase are reciprocally regulated. When
glycogen synthase dephosphorylated , it activates(a); glycogen phosphorylase dephosphorylated, it inhibited(b). And visa versa. Lack of rubisco,2+sedoheptulose 1,7-BPase, Ru5P kinase, animals can not synthesize CO2 into glucose.4 calvin cycle enzymes were
indirectly regulated by light: Ru5P dehydrogenase. Activated while 2Cys S-S bond cleaved byferredoxin(light energy)  Light, high pH and high [Mg ] activates FBPase-1  C4 photosynthesis: pyruvate+ATP PEP(+AMP+PPi) (+CO 2) oxaloacetate(+Pi) 
(+NADPH) malate (enter bundle sheath) pyruvate +CO 2+NADPH  ADP-Glucose is the substrate for starch synthesis in plant and for glycogen synthesis in bacteria  Starch(n)+G1P+ATPstarch(n+1)+ADP+2Pi  UDP-Glucose is the substrate for sucrose
synthesis in the cytosol of leaf cells.  F6P+UDP-glucosesucrose F6P( PFK-2)F2,6BP; F2,6BP(FBPase-2)F6P  PFK-2 was activated by Pi and inhibited by 3-PGA  FBPase-1 was inhibited by F2,6BP  Sucrose 6-phosphate synthase : less active
: when phosphorylated  Lactose synthesis: UDP-galactose and glucose  UDP glucose: intermediate of glucuronate and VC Cellulose synthesis: initiated by lipid-linked primer, UDP-glucose
 Lipid BiosynthesisMalonyl-CoA comes from acetyl-CoA and CO2 , irreversible acetyl-CoA carboxylase Acetyl-CoA carboxylase in bacteria has 3 separate subunits;animal has a single MFP; plants have both.Contain biotin. ACP
 TheCO2 formed during condensation process is the same CO 2 that has been added to acetyl-CoA and generates malonyl-CoA.  The dehydration process formed atrans double bond in FA syn .Fatty acid synthase complex: ACP; KS (β-ketoacyl-ACP-synthase);
MT (Malonyl-CoA-ACP transferase); KR (β-ketoacyl-ACPreductase); HD (β-hydroxyacyl-ACP dehydratase); ER (enoyl-ACP recuctase); AT (acetyl-CoA-ACP transacetylase)The main FA synthesis process formspalmitate (16 C) Each addedmalonyl-CoA requires 2 NADPH
 In photosynthetic cells of plants the FA synthesis go inct stroma  For FA synthesis, the acetyl-CoA were shuttled out from mitochondria as the form of citrate. Citrate, pyruvate andmalate can pass through mt membranes, and citrate was formed by oxaloacetate
and acetyl-CoA. Animal FA synthesis rate-limiting step was acetyl-CoA carboxylase, which covalently regulated by citrate binding and phosphorylation.Phosphorylation was triggered on by glucagon and epinephrine.Citrate binding activates the process while
glucaton/epinephrine, palmitoyl-CoA inhibit . Plant/bacteria acetyl-CoA carboxylase was stimulated by increased pH and [Mg2+]  Long-chain saturated FAs are synthesized from palmitate on ERMammals can not synthesize linoleate18:2(∆9,12) and α-linolenate
(∆9,12,15) Eicosanoids are formed form 20-carbon polyunsaturated FAs arachidonase by cyclooxygenases and peroxidases Triacylglycerols and glycerophospholipids are synthesized fromthe same precursors: acyl-CoA and L-glycerol-3-phosphate.
 First the diacylglycerol-3-phosphate ( phosphatidic acid ) was formed, then to triacylglycerols/glycerophospholipids. Release oftriacylglycerol stimulated by glucagons/epinephrine  Insulin stimulates the synthesis of fatty acids and acetyl-CoA.Glycerol-3-phos
was formed form dihydroxyacetone phosphate through glycerol-3-phosphate dehydrogenase. The rate-limit step of glyceroneogenesis was PEP carboxylase 2 strategies in the forming of phosphodiester bond of phospholipids: 1) diacylglycerol activated with CDP
; 2) head group activated with CDP. Prokaryote can use 1) only. Phosphaditylserinephosphadityethanolaminephosphatidycho -line, the CH3 in choline was donated by adoMet.  Plasmalogens contain ester(double bond) -linked R group, oxidized by mixed-function
oxidase.The condensation of palmitoyl-CoA and serine produce β-ketosphiganine, then sphinganines.Then double bond and R group was introduced. Finally ceramide, cerebroside (Glu) and sphingomyelin (choline)  Isoprene was the basic of cholesterol. All
carbons by acetyl-CoA. Synthesis of cholesterol has 4 steps: 1)acetatemevalonate (NADPH); 2)mevalonateactivated isoprene; 3)activated isoprene to squalene(NADPH);4)squalene to cholesterol(NADPH).
 LDL was most rich in cholesterols while HDL has the least.LDL enters the cell by endocytosis.
 Biosynthesis of amino acids, NAcs and other.  Each N2 fixation requires 16 ATP Nitrogenase complex contains: 4Fe-4S, Iron-molybdenum cofactor (1Mo, 7Fe, 9S, 1homocitrate). Glutamine synthease is the primary regulatory in N metabolism. When
2Gln synthease subunits adenylylated, activity goes low. PII-UMP stimulates deadenylylation. Cys residue played role in Gln amidotransferase, 2 domains. SO2-4 APSPAPSPAPSO23 S Cys Chorismate is a key intermediate to synthesis Trp, Phe & Tyr.
 Amino acid biosynthesis is under allosteric regulation.  Concerted inhibition: the overall effect is more than additive.Glycine is a precursor of porphyrins. Heme is the source of bile pigments.δ-Aminolevulinate is the precursor of porphyrins, its synthesis
requires tRNA-Glu.Jaundice: leakage of bilirubin.  Glutathione peroxidase contains Se. Arginine is the precursor of biosynthesis of NO. Aspartate transcarbamoylace under allosteric regulation of C/ATP.The salvage pathway of NAc:alkaline base+PRPPNMP+PPi
 Metabolism regulations and hormones Radioimmunoassay (RIA): calculate the [bound(radiolabeled)/unbound] value to determine the hormone amount in unknown samples.  NO: cytosolic receptor guanylate
cyclase) & 2nd messenger cGMP  Cori cycle:lactate
(
generated in skeletal muscles were transferred into liver and been recycled as glucose. Neuronscan use keto bodies (β-hydroxybutyrate) The pancreas secretesinsulin or glucagon to response blood G. Thestarvation leads to the high ketone concentrations
concentrations in blood. Insulin activates the GLUT4 glucose transporters on membrane.  Acetone come from spontaneous decarboxylation of acetoacetate Diabetes, accumulation of acetyl-CoA, leads to the overproductionof acetoacetate and β-hydroxybutyrate.
 Leptin was produced in adipocytes and acts on hypothalamus to curtail(reduce) appetite; stimulates production of anorexigenic hormones; regulates gene expression. Defective causes obesity. Adiponectin acts through AMP-dependent kinase (AMPK).
Defective leads less sensitive to insulin. Phosphorylated ACC(acetyl-CoA carboxylace) is inactive, AMPKphosphorylates ACC.
Enzymes use NAD as cofactor:Isocitrate dehydrogenase; α-ketoglutarate dehudrogenase; G-6-P dehydrogenase; Malate dehydrogenase; Glu dehydrogenase (use either NAD or NADP); glyceraldehydes-3-phosphate (PGAld) dehydrogenase; lactate dehy; alcohol dehy
Enzymes use FAD as cofactor Fatty acyl-CoA dehydrogenase; dihydrolipoyl dehydrogenase; succinate dehydrogenase; thioredoxin reductase Enzymes use FMN as cofactor NADH dehydrogenase (Complex I); glycolate dehydrogenase
Diseases Deficiencies in carnitine: inability to transport FAs, hemodialysis,organic aciduria, weakness CPT I: affect liver and reduce FA oxidation and ketogenesis CPT II: recurrent muscle pain, fatigue and myoglobinuria MCAD deficiency: vomit, lethargy & coma,
prevent fasting Refsum's Disease: inherited disorder, lack mt α-oxidizing enzyme,phytanic accumulation, cerebellar ataxia, nerve deafness.LHON: defects in mitochondria encoded cytb gene.