exam 2 learning objectives
epimer
*subtype of diatereomers *differ in configuration at exactly one chiral carbon -Lobry de Bruyn-van Ekenstein rxn: C2 epimerization under alkaline conditions. changing from one epimer to another via enediol intermediate
reduction of carbohydrates
-sugar alcohols prepared this way (-itols) -reduction of carbonyl groups of aldoses and ketoses with NaBH4 -ketoses produce racemic mixture, aldoses produce alditol
Know the general features of the reactions that build polysaccharides
-sugar donors in glucoconjugate biosynthesis catalyzed by glycosyl transferases are sugar nucleotides -UDP-galactose + glucose via lactose synthase --> lactose o Need energy to make polysaccharides-- charge up monosaccharide by attaching uracil (this case UDP) to create high energy phosphoric anhydride bond (provides energy to attach glucose to make lactose)(becomes nucleotide) § kinases put extra phosphates onto UMP to make UDP -nucleoside di/monophosphate used depends on the particular sugar involved
Understand the general features of monosaccharide structure (don't have to identify specific names given a structure)
-(CH2O)n, n>2 -polyhydroxy aldehydes or ketones (aldose or ketone)(3-7 carbon atoms w these groups) -have at least one asymmetric center -have the ability to exist in linear or ring form -can form polymeric structures via glycosidic bonds -can form multiple H bonds with water or other molecules in environment -
Pentose Phosphate pathway
-1: glycose 6P dehydrogenase converts G6P to 6-phospho-gluconolactone (committed step) -2: gluconolactonase turns 6PG into 6-phospho-gluconate -3: 6-phosphogluconate dehydrogenase, oxidative decarboxylation of 6PG to keto form then R5P -4: phosphopentose isomerase converts ketose to aldose -5: phosphopentose epimerase epimerizes at C3 to make xylulose form -6: transketolase transfers 2 carbon units to R5P to make sedoheptulose 7 P (thiamine coenzyme) -7: transaldolase transfers 3 carbon units from S7P to glyceraldehyde 3P produced from breakdown of R5P in last reaction to get F6P (can go into glycolysis) -8: transketolase again from xylulose to erythrose produced in last rxn to make F6P and G3P -and so on -last steps reversible in cytoplasm -make DNA and RNA out of product R5P, can also make energy out of it -also makes glycolytic intermediates
gluconeogenesis steps
-1: pyruvate carboxylase turns pyruvate and bicarb + ATP to oxaloacetate, biotin cofactor (avidin protein inhibits), in mitochondria (turned to malate to escape then ox back to oxaloacetate in cytosol). Part B of this is PEP carboxykinase rxn, converts oxaloacetate to PEP (requires a lot of energy, why pyruvate carboxylase consumed ATP-- drives carbon so PEP carboxykinase could use it to form PEP) -2: enolase rxn turns PEP to 2-phosphoglycerate -3: phosphoglycerate mutase turns 2PG to 3PG -4: phosphoglycerate kinase turns 3PG to 13BPG using ATP -5: glyceraldehyde-3-phosphate dehydrogenase turns 13BPG to G3P (reduction) -6: triose phosphate isomerase turns G3P to DHAP -7: aldolase turns DHAP + glyceraldehyde-3-phosphate to F16BP -8: fructose 1,6-bisphosphatase hydrolysis of F16BP to F6P (phosphoglucose isomerase can convert this to G6P) -9: glucose-6-phosphatase: converts G6P to glucose
Know why coupled reactions are important in metabolism/glycolysis
-Coupled reactions convert some, but not all of the metabolic energy of glucose into ATP -Coupled reactions involving ATP hydrolysis are also used to drive the glycolytic pathway § Some reactions unfavorable so coupling makes the overall rxn favorable
Haworth projections
-For the D-sugars, the anomeric hydroxyl group is below the ring in the alpha-anomer and above the ring in the beta-anomer. For l-sugars, the opposite relationship holds. -Alpha is biggest C1 sub and opposite sub on diff sides of ring, beta is that on same side -Substituents on left in fischer are above ring in haworth, those right on fischer below ring in Haworth
metabolic maps
-Indicates reactions of intermediary metabolism and the enzymes that catalyze them -each intermediate is black dot, each enzyme is a line -A dot connected to a single line must be a nutrient, a storage form, an end product, or an excretory product -A dot connected to just two lines is probably an intermediate in one pathway and has only one fate in metabolism
NAD/NADH/NADP/NADPH
-NADPH needed for synthesis of fatty acids (highly reduced energy store). oxygens of fatty acids reduced with NADPH from PPP -enzymes that function primarily in reductive direction use NADP/NADPH pair instead of NAD/NADH bc NADP/NADPH ratio is much lower (reduced form more prevalent)
protein phosphatase 1
-PP1 -reverses effects of kinases on phosphorylase, inc rate of glycogen synthesis (activates glycogen synthase) and decreases rate of breakdown (inactivates glycogen phosphorylase) -when glucose binds phosphorylase a in liver it exposes phosphate group to PP1, which only cleaves of phosphate group when phosphorylase a binds glucose. PP1 released from phosphorylase b and then begins to dephosphorylate glycogen synthase (activates it) -activated by insulin, inhibited by epinephrine -insulin-sensitive PK phosphorylates the G subunit of PP1 at a different site than PKA, so it's more active (dephospho glycogen synthase, phosphorylase kinase, and phosphorylase which inc glycogen syn and dec glycogen breakdown)
understand what and how the pentose phosphate pathway produces reducing power and different sized monosaccharides
-PPP uses glucose 6P to produce 3-7 carbon sugars (including ribose-5-phosphate needed for nucleotide biosynthesis), in process reduces NADP+ to NADPH which is needed for reductive biosynthesis (via oxidizing G6P to 5 carbon sugar) -overall produces 6 NADPH, 3 pentose, 3 CO2 from 3 glucose -first 3 rxns involve oxidation of G6P to ribulose 5P with the release of CO2 and production of 2 NADPH -high levels of these enzymes in liver and adipose cells, not in muscle which uses glycolysis and CAC for energy -regulated at first step G6P dehydrogenase by conc of NADP+
cyclic form pyranose
-aldoses cyclize to form pyranoses (bc similar to pyran) -reversible rxn catalyzed by acid or base -alcohol turns to aldehyde which turns to hemiacetal which then undergoes intramolecular rxn to form cyclic hemiacetal (dehydration synthesis) -alpha-linear-beta forms in equilibrium bc bond is labile -pyranose favors chair then boat conformations
The principles of stereochemistry including L and D designations.
-aldoses w at least 3 carbons and ketoses w at least 4 have chiral centers -D or L not necessarily dex/levo, that depends on highest # asymmetric carbon -in fischer projection L form is hydroxyl group on left, D form (predominant in nature) is hydroxyl on right ON HIGHEST # ASYMM CARBON (reference carbon) -Substituents on left in fischer are above ring in haworth, those right on fischer below ring in Haworth -D and L are mirror images of e/o
Know the general features of anabolic and catabolic metabolic pathways
-anabolic rxns are synthetic processes in which the varied and complex biomolecules are assembled from simpler precursors (energy-requiring) -catabolic rxns involve the oxidative degradation of complex nutrient molecules (energy-yielding) -they are interrelated (pathways converge to a few end products, shared intermediates)
why furanose and pyranose result in another chiral center designated the anomeric carbon
-bc double bond on O disappears and that carbon now has 4 different substituents (asymmetric) -addition of asymmetric center alters the optical rotation properties of the molecule. o The optical rotation of a freshly prepared solution of D-glucose (and most other reducing sugars) gradually changes until it reaches a constant value for a given concentration (mutarotation), which indicates structural change
why is having branches in glycolysis advantageous?
-branching provides more non-reducing ends for the addition or 87% removal of glucose subunits -faster
Understand the metabolic fates of NADH produced in glycolysis
-can be recycled via aerobic or anaerobic pathways § If O2 is available (aerobic conditions), NADH is re-oxidized in the electron transport pathway, making ATP in oxidative phosphorylation § In anaerobic conditions, NADH is re-oxidized by lactate dehydrogenase (LDH), providing additional NAD+ for more glycolysis · Gives place to dump the hydride ion (bc more NAD needs to be made)
what is the PFK reaction known as?
-committed step in glycolysis (not reversible), second priming reaction
Know the difference between epimerization and isomerization.
-epimerization is change from mannose to glucose bc they're epimers (diastereomers that differ in configuration at one chiral carbon), isomerization is change from glucose to fructose bc they're isomers (same atoms but different atom arrangements)
formation of cyclic AMP
-epinephrine stimulates adenylate cyclase. ATP loses two phosphates via adenylyl cyclase, creates cAMP and pyrophosphate
racemic mixtures
-equal concentrations of two enantiomers -will not be optically active because two enantiomers' rotations cancel each other out -§ Racemic mixtures of enantiomers are often separated by derivatizing the mixture with a chiral reagent thereby converting the components to a mixture of diastereomers which can then be separated. The original compounds are then regenerated.
Why store such a short supply of glycogen when most of our energy reserves are stored as fat?
-fat cannot be mobilized as fast as glycogen -fat cannot supply enough energy in the absence of oxygen -fat cannot be converted to glucose to maintain blood glucose levels
diastereomers
-stereoisomers that are not mirror images of each other. In general they have different chemical and physical properties and can be separated from each other. If they differ at only one chiral center then they are epimers.
why does blockage of the final step in gluconeogenesis cause an increase in glycogen storage?
-final step is glucose-6-phosphatase which -A greater amount of Glucose-6-Phosphate in the cytoplasm causes a greater amount of Glucose-1-phosphate, which reduces the phosphorolysis of glycogen (resulting in lots of glycogen being made). G6P also can't be converted to glucose so can't leave the cell. also harder to breakdown G1P and glycogen because LeChat pushes rxn forward. -cause of von gierke disease (treatment is feeding all the time so blood glucose never goes down) -also causes more G6P to go into glycolysis and PPP, which causes hyperalaninemia, hyperlipidemia, lactic acidemia, and hyperuricemia
fehling's reaction
-for aldehyde but can also detect ketones after tautomerization (isomerization) -blue copper in solution + reducing sugar + heat + alkali (sugar is oxidized and copper reduced) -red precipitate is pos test for aldehdye -Fehling's solution is CuSO4 -Quantifying amt of oxidizing agent reduced by sugar can be used to determine conc of sugar (Diabetes mellitus-- analyze reducing sugars in patients for this reason^ (gives blood/urine glucose)
Understand how hormonal alterations affect rates of gluconeogenesis
-gluconeo stimulated by glucagon and epinephrine (which stimulate glycogen breakdown bc need more glucose), inhibited by insulin (which stimulates glycogen storage bc too much glucose)
what happens when the first step of the pentose phosphate pathway is deficient in humans?
-glucose 6 phosphate dehydrogenase deficiency, NADPH not made which is used to recycle glutathione which is an antioxidant that prevents oxidative damage by hydrogen peroxide and to hemoglobin and shit -red blood cells are more sensitive to oxidation and lysis bc they lack mitochondria, membrane integrity is compromised -affects 11% of African American males, females in Africa have inc resistance to malaria -certain drugs, bacteria/viral infections can trigger it
Know the key regulation points of gluconeogenesis
-glucose-6-phosphatase substrate level control: at higher G6P concentrations the reaction rate increases bc km is higher than the normal range -fructose 1,6-bisphosphatase: catalyzes hydrolysis of F16BP to F6P (reverse in glycolysis is PFK). citrate activates, fructose 2,6-bisphosphatate and AMP inhibit -pyruvate carboxylase-PEP +carboxy kinase pair: activated by acetyl-coA -glyc and glucose are reciprocally regulated, so regulatory molecules that inhibit glyc activate gluconeo and vv -**PFK 2 synthesizes and degrades F26BP so activated by F26BP, PFK1 is the one in glycolysis
metabolic/intracellular glycogen breakdown
-glycogen phosphorylase: phosphorolysis at a nonreducing end of a glycogen polymer ie cleaves glucose residue off by addition of inorganic phosphate to break alpha 1-->4 linkage (if glycogen breakdown were hydrolytic and yielded glucose as a product, it would be necessary to phosphorylate the product glucose, which would expend ATP, to initiate its glycolytic degradation -debranching -produces G1P, which phosphoglucomutase converts to G6P needed for glycolysis
Understand the differences and similarities in the enzymatic steps of glycolysis and gluconeogenesis
-glycolysis: glucose to 2 pyruvate, creates 2 ATP, reduces NAD to NADH, active when energy low, 10 steps, pyruvate to AcCoA before krebs -gluconeogenesis: 2 pyruvate to glucose, consumes 4 ATP and 2 GTP, oxidizes NADH to NAD, active when energy in cell high, 11 steps, AcCoA not used -3 rxns from glycolysis not used in gluconeo are those with very low DG (hexokinase, PFK, pyruvate kinase)
why is the nature of glycosidic bonds important?
-glycosides (linked sugar acetals) form glycosidic bond, v stable so does not mutarotate (anomeric carbon stabilized/can no longer linearize)
know how the PPP operates with differing cellular needs
-if both R5P and NADPH are needed then the first four PPP rxns dominate, NADPH produced and R5P is principal product -if more R5P than NADPH needed by cell, the last couple steps in the PPP are run backwards to decrease amt of NADPH (bypassing oxidative reactions) -if more NADPH than R5P needed, R5P recycled to produce glycolytic intermediates -if both NADPH and ATP are needed but not R5P, R5P is recycled to glycolysis and F6P/G3P made produce ATP and pyruvate then pyruvate goes through TCA cycle to make more ATP
Understand the metabolic fates of pyruvate produced in glycolysis
-in animals converted to acetyl coA, which is then oxidized in TCA cycle to produce CO2 -in anaerobic conditions converted to lactate -alcoholic fermentation converts it to ethanol and CO2 (yeast), means for regenerating NAD+ for glycolysis
know the reactions that make glycogen
-in cytosol, G6P brought into the cell and converted to G1P via phosphoglucomutase initiated on glycogenin -UDP glucose used (UDP charges glucose up), made from G1P and UTP via UDP-glucose pyrophosphorylase -initiated on glycogenin -transfer of glucose unit from UDP-glucose to a tyrosine in glycogenin protein (reducing end attached to protein), glycogenin autocatalytically extends the glucan chain 7 glucose units, then glycogen synthase takes over (extends) along with glycogen branching enzyme (takes 7 glucose segment ends off of 1 to 4 polymers and makes 1 to 6 linkage at branch point)
Understand how the cell hormonally regulates glycogen production and break down
-in fasting/exercising state glycogen degradation goes up and synthesis down, VV for adequate diet/rest -hormonal: mediated by reversible phosphorylation of several different enzymes in regulatory cascades that are responsive to insulin (response to inc glucose in blood, activates PP1 to dec glycogen breakdown), glucagon (made when gluc is low, activates glycogen breakdown but not in muscle, inc glyc P and dec glyc S activity), and epinephrine (triggers breakdown in muscle and liver, activates glycogen phosphorylase and inhibits synthase) -protein kinase A binds calcium in response to muscle contraction to become partly active, fully activates via binding of hormone-triggered released cyclic AMP (two regulatory subunits of PKA bind cAMP, which releases its active catalytic subunits). PKA phosphorylates phosphorylase kinase, which activates it. this then hydrolyzes ATP to turn inactive phosphorylase b into active phosphorylase a (w phosphate), which breaks apart glycogen via phosphorylation (OR phosphorylates glycogen synthase to turn it to inactive b form)
F26BP regulation
-in glycolysis F26BP increases the affinity of PFK for F6P substrate, reverses inhibition of PFK by ATP, and restores hyperbolic dependence of enzyme on substrate concentration -in gluconeogenesis inhibits F16BP
Understand where glucose is stored as glycogen
-stored in liver to maintain blood glucose levels (varies between meals, lasts 12-24 hours) and in muscle to serve as a fuel reserve for ATP synthesis
Know how common polysaccharides are linked
-include not only those substances composed only of glycosidically linked sugar residues, but also molecules that contain polymeric saccharide structures linked via covalent bonds to amino acids, peptides, proteins, lipids, and other structures -starch (energy storage): amylose (linear) and amylopectin (branched every 12-30 residues) forms. amylose 1,4 linked so bond takes one reducing end away, poorly soluble in water but forms micellar suspensions in which it is helical-- iodine fits into this to produce blue color (test for starch). amylopectin branches are alpha1-->6
dietary glycogen breakdown
-involves alpha amylase: in saliva and pancreatic juice, hydrolyzes alpha 1-->4 linkages of amylopectin and glycogen at random positions -creates limit dextrins and maltose: highly branched polysaccharides that are left after extensive exposure to alpha amylase -debranching enzyme: makes up for where amylase can't break, oligo(alpha1,4-->1,4) glucanotransferase removes trisaccharide unit and transfers to end of another nearby branch leaving single residue branch, alpha(1-->6)glucosidase cleaves single residue from chain
cyclic form furanose
-ketoses cyclize to form furanoses (bc similar to furan) -alcohol turns to ketone which turns to hemiketal which then undergoes intramolecular rxn to form cyclic hemiketal (dehydration synthesis) -chair, boat, skew, half chair conformations
common disaccharide linkages
-maltose and cellobiose disaccharides 1-->4 linked (C1 of one gluc linked to C4 Oxygen of other)(beta or alpha within name here refers to configuration of glycosidic bond, why you can breakdown maltose but not cellobiose bc it has alpha)(maltose breakdown of glycogen, cellobiose of cellulose) -trehalose (disaccharide) prevents crystallization of water so protects insect from damage in freezing temps -lactose intolerance-- if you can't break down lactose and absorb it into blood stream it goes and powers bacteria in the colon, causing issues (overfeeding them) -glycogen (energy storage): alpha(1-->6) branches every 8-12 residues, in liver helps regulate blood sugar and muscle gives quick energy (bc don't need oxygen to make ATP from glucose), gives red-violet color with iodine (like amylopectin)
Pellegra
-nicotinamide in NAD whatever derived from niacin, pellagra is deficiency of this -corn disease-- treating with alkali released niacin in corn, why breads and grains now are fortified with niacin
Know the general features of the reactions that break down polysaccharides
-phosphorylase release: starch phosphorylase reactions cleaves glucose residues from amylose, producing α-D-glucose-1-phosphate, an energy source for the organism (mobilization) -§ Gluc 1 phosphate can be converted to gluc 6 phosphate which enters into glycolysis · Phosphorylation rather than hydrolysis saves an ATP -glycogen can be hydrolyzed by both alpha/beta amylases and glycogen phosphorylase
PET tumor diagnosis
-positron emission tomography -tumors show very high rates of glycolysis o Metabolites labeled with 18F can be taken up by human cells (in the brain, for example) o Decay of 18F results in positron emission o Positron-electron collisions produce gamma rays o Detection with gamma ray cameras provides 3D models of tumor extent and location o 2-[18F]fluoro-2-deoxy-glucose, used for this purpose, is a substrate for hexokinase
understand the chemical principles and features of the second phase of glycolysis
-produces two pyruvates and 4 ATP, involves two v high energy phosphate intermediates (1,3-biphosphoglycerate 13BPG and phosphoenolpyruvate PEP) -rxn 6: glyceraldehyde 3P dehydrogenase, G3P oxidized to 13BPG, overall reaction involves formation of carboxylic-phosphoric anhydride and reduction of NAD+ to NADH as well as covalent catalysis and nicotinamide coenzyme (also site of action of arsenate) -rxn 7: phosphoglycerate kinase, transfers a phosphorylation group from 13BPG to ADP to form an ATP (pays off ATP debt from beginning) and 3PG, coupled with 6 and 4/5 rxns (v exergonic so pulls them along), substrate level phosphorylation (ADP phosphorylated at expense of G3P), beginning bond is higher energy than ATP phosphate bond so goes forward -rxn 8: phosphoglycerate mutase, catalyzes a phosphorylation group transfer from C3 to C2 to make 2PG (repositions phosphate to make PEP in following rxn via enolase and prepares for syn of 2nd ATP) -rxn 9: enolase, conversion of 2PG to PEP (a form from which more energy can be released in hydrolysis) via dehydration (makes high energy phosphate in preparation for ATP synthesis in rxn 10) -rxn 10: pyruvate kinase, transfer of phosphoryl group from PEP to ADP to make ATP and pyruvate (last pyruvate branch pt), large negative DG bc spontaneous conversion of enol tautomer of pyruvate to more stable keto form
Understand the essential features of glycolysis
-rapid breakdown of glucose caused by catalysis via intracellular enzymes -hydrolyzes ATP to release energy and push reactions forward -10 enzyme catalyzed steps -products are 2 pyruvate, 2 ATP, and 2 NADH (net) -Keq alters the actual free energy of a reaction from the standard state free energy change (so concentrations of things within the cell can make favorable/unfavorable, could differ from standard state)
red vs white muscle fibers
-red: many mitochondria and myoglobin, glucose converted primarily to pyruvate that can be completely oxidized to CO2 and water, needs oxygen, capable of sustained activity but stores glycogen for periods of increased demand -white: few mitochondria and little myoglobin, breaks down glucose primarily to lactate very rapidly, capable of high energy output for short periods
why is gluconeogenesis not just the reverse of glycolysis?
-reverse of glycolysis is thermodynamically unfavorable, so energetically unfavorable steps in reverse glycolysis rxn are replaced and energy is added in the form of GTP and ATP to give a different reaction -both processes must also be reciprocally regulated so one is inhibited when the other is active
General names by number of carbons and ketose vs. aldose.
-ribose = aldopentose -glucose and mannose = aldohexoses -D fructose most common ketoses (part of glycolytic cycle) -prefix is aldo or keto to denote aldehyde or ketone group, infix is number of carbons
enantiomers
-stereoisomers that are mirror images of each other. The mirror image of an enantiomer cannot be superimposed on itself -enantiomers have identical chemical and physical
amino sugars
-sugars with amino group at C2 instead of hydroxyl -found in many oligos and polys (chitin) -muramic acid in cell membranes and bacterial cell walls (hydroxyl group of lactic acid moiety makes an ether linkage to C3 of glucosamine) -sialic acids: N acetyl and N glycolyl derivatives of neuraminic acid (amine isolated from neural tissue). Neuraminic forms CC bond btw C1 of N acetyl-mannosamine and C3 of pyruvic acid -Laetrile
fermentation
-the production of ATP energy by reaction pathways in which organic molecules function as donors and acceptors of electrons -w/o this glycolysis would stop
why do organisms store carbohydrates (energy producing sugars) in the form of polysaccharides rather than as monosaccharides?
-to lower the osmotic pressure of the sugar reserve (osmotic pressure depends only on numbers of molecules, so is greatly reduced by formation of a few polysaccharide molecules out of many many monosaccharide units) -ie why glucose is combined to form glycogen in cells rather than being stored as glucose
anomers
-two cyclic sugars sugars (monosaccharide isomers) that differ only in the configuration of the hemiacetal or hemiketal carbon (anomeric carbon atom)
Know how cells regulate glycolysis
ALL LARGE NEG DG SITES -hexokinase regulation: hexokinase is normally working when glucose low bc product inhibited, glucokinase working when cell is rich in glucose bc not product inhibited. also allosterically inhibited (binding at diff site) by product G6P -PFK: controls rate of glycolysis (inc activity when energy status low and VV), ATP inhibits and AMP reverses that inhibition (AMP accumulation means starving for energy, it's usually not in the cell. ATP--ADP--AMP). citrate inhibitor, F26BP activator. behaves cooperatively at high conc ATP -pyruvate kinase: activated by AMP and F16BP, inhibited by ATP and acetyl CoA
what do kinase reactions have as a reactant or product that phosphatase reactions do not?
ATP
compared to glycolysis, gluconeogenesis requires more of what?
ATP, enzymatic steps, and cellular compartments
isomerase
An enzyme that catalyzes the transformation of compounds into their positional isomers. In the case of sugars this usually involves the interconversion of an aldose into a ketose, or vice versa.
toxic action of arsenate
arsenate replaces phosphate in the G3P-DH reaction forming 1-arseno-3-phosphoglycerate, breaks down to 3-phosphoglycerate which bypasses phosphoglycerate kinase rxn 7 which makes glycolysis produce no net ATP -arsenic right below phosphorous on P table
why is hexokinase not the most important site of regulation in glycolysis?
G6P is common to several metabolic pathways (branch point), so can get this from other sources
which is a requirement needed for reciprocal regulation of opposing pathways (catabolism and anabolism)?
at least one step must be carried out by a different enzyme (ensures that they can be regulated independently)
nucleotide diphosphate kinase
catalyzes NDP + ATP --> NTP + ADP
enantiomer of D glucose
L glucose
what is the most abundant organic polymer on earth?
cellulose
the major chemical difference between cellulose and glycogen is
cellulose has beta 1-4 linkages while glycogen has alpha 1-4 linkages
what does fermentation provide for glycolysis?
NAD+ (NADH reoxidizes to NAD+ by reduction of pyruvate to lactate, then lactate recycled to glucose in the liver)
the oxidation of glucose to pyruvate shown in the overall glycolysis equation requires donating 4 electrons to another molecule, which product ends up with them?
NADH
Understand the chemical principles and features of the first phase of glycolysis
OVERALL: converts glucose to two G3P molecules -rxn 1: hexo/glucokinase, priming rxn (put ATP in to get more later bc makes phosphorylation of glucose spontaneous), DG large and negative bc ATP hydrolysis, phosphorylates glucose -rxn 2: phosphoglucoisomerase, converts G6P to F6P (carbonyl O of G6p shifted from C1 to C2, aldose to ketose with ene-diol intermediate) -rxn 3: phosphofructokinase, ATP drives second phosphorylation at C1 hydroxyl to make F16BP, DG large and negative -rxn 4: FBP aldolase cleaves F16BP to make DHAP and glyceraldehyde 3 phosphate (G3P) (triose phosphates) via removal of proton from beta hydroxyl group and elimination of enolate anion, standard state unfavorable but actual is close to eq bc conc of reactant (1) and products (2) make it so -rxn 5: triose phosphate isomerase, only G3P goes into second phase of glycolysis so DHAP converted to this
oxidation of carbohydrates.
OXIDATION -ketoses (like fructose) not oxidized/can't reduce except in alkaline solution by Ag+ to give metallic silver or by Cu2+ to give Cu+ reducing sugars -sugars with free anomeric carbon atoms (aldoses) good reducing agents, convert sugar to sugar acid via addition of Br2 and water (aldonic acid)/dil HNO3 (2 oxidations for aldaric acid) -type of acid formed depends on carbon oxidized
mutase
Relocates a functional group within a molecule (mutation of a chemical intermediate)
structural polysaccharide structures
cellulose: -chains with hydrogen bonds between the sheets (intrachain and interchain) -when stacked, chains are staggered to give strength and stability chitin: -chains can be parallel or antiparallel -repeating units N acetyl D glucosamines in beta 1-->4 agarose (double helix with threefold screw axis and central cavity for water molecs) and agaropectin, alginates, glycosaminoglycans (heparin-- prevents blood clots, another kind helps joints)
what is the first committed step in glycolysis?
fructose-6-phosphate ---phosphofructokinase1(PFK-1) --> fructose 1,6-bisphosphate
how does hexokinase keep glucose in the cell
glucose is neutral so can freely cross cell membrane. the phosphorylation of glucose gives the molecule a negative charge, which keeps ICF glucose concentration low so glucose diffuses into the cell -site of regulation bc not at equilibrium
very little hormone is needed for a large cellular response. what contributes to this "amplification" of signal for the hormone epinephrine and IDK ADD?
hormone binding to the receptor stimulates adenylyl cyclase to make hundreds of molecules of cAMP which can turn on hundreds of kinases to phosphorylate hundreds of proteins resulting in the amplified signal
what can be produced from the final product of glycolysis with one enzymatic reaction?
lactate
phosphofructokinase is activated by what conditions?
low ATP levels
stereoisomers
molecules with the same molecular formulas and order of attachment of constituent atoms but which differ in the arrangement of these atoms in space
in a well-fed and well-rested normal individual, what has the greatest total amount of glycogen stored?
muscle (less percent wise but total overall more)
what makes red muscle fibers red?
myoglobin
dextrans
o If you change the main linkages between glucose from alpha(1,4) to alpha(1,6), you get a new family of polysaccharides - dextrans § Isomaltose repeating unit -component of dental plaque--protection for oral bacteria
Why not just store free glucose instead of making glycogen?
o Would require the expenditure of a lot of energy (ATP) to bring glucose into a cell against a concentration gradient o High intracellular glucose concentration would cause the cells to take up water and lyse (400mM glucose stored as glycogen is only 0.01uM)f
what enzymes use glucose-6-phosphate as a substrate?
phosphoglucomutase, phosphoglucoisomerase, glucose 6 phosphatase, glucose 6 phosphate dehydrogenase
phosphoenzyme
phosphoryl group is covalently bound to histidine at active site
substrates of gluconeogenesis
pyruvate, lactate, TCA cycle intermediates (like oxaloacetate), most amino acids. NOT acetyl-coA (pyruvate degraded to this, what goes into Krebs), fatty acids (yield only acetyl-coA upon degradation), lysine and leucine (also only make acetyl coA) **acoA not substrate bc in CAC most of it blows off as CO2, so can't go back into gluconeo (why you can't convert fat into glucose)(glycoxylate cycle in plants and bacteria gets around this by producing malate, which can be converted to oxaloacetate then glucose)
in organisms lacking the glycoxylate cycle, what can be used for gluconeogenesis?
pyruvate, lactate, oxaloacetate
phosphatase
removes phosphate
which disaccharide is not considered a reducing sugar and why?
sucrose-- only one without one free unsubstituted anomeric carbon. no free OH group so no reducing end
what does Km mean?
the concentration of a substrate needed to create a half-maximal reaction velocity -higher km = more substrate needed
how can glycolysis move forward when there are individual steps that have positive free energies?
the deltaG values of each step are based on average values of metabolite concentrations and sometimes those change to make deltaG go below zero
mutarotation of monosaccharides is caused by what process?
the epimerization of the monosaccharide (new chiral center being made at the anomeric carbon, change from alpha to beta)
what bond is made first by de novo purine biosynthesis?
the glycosidic bond between the base and ribose -bond btw anomeric carbon of ribose and N1/9 of base
kinases
transfer gamma-phosphate of ATP to nucleophilic acceptors -catalyzes phosphorylation or dephospho rylation of a molecule using ATP or ADP respectively
dehydrogenase/oxidase
transfer of electrons, ie NADH/NAD+
why is it not possible for humans to digest cellulose?
we don't have the capacity to break the beta bonds in cellulose--don't have the bacterial cellulase like ruminant animals do
2-3 BPG and phosphoglycerate kinase
• 2,3-BPG is made by reactions that detour around the phosphoglycerate kinase reaction o 2,3-bisphosphoglycerate is an important regulator of hemoglobin (helps lower oxygen affinity to allow release) § Stabilizes deoxy form o 2,3-BPG is formed from 1,3-BPG by bisphosphoglycerate mutase o 3-phosphoglycerate is then formed by 2,3-bisphosphoglycerate phosphatase o Most cells contain only a trace of 2,3-BPG, but erythrocytes typically contain 4-5 mM 2,3-BPG (so hemoglobin can dump off oxygens more readily)