Biochem exam 3
overall reaction for gluconeogenesis
2 pyruvate + 6 ATP --> glucose + 6 ADP + 6 Pia
the cellular energy currency
ATP - converted from energy derived from fuels or light
ATP-ADP cycle
ATP is the immediate donor of free energy for biological activities. However, the amount of ATP is limited so ATP must be constantly recycled from ADP to provide energy to power the cell. fundamental mode of energy exchange in biological systems
fermentation
ATP-generating processes in which organic compounds act as both donors and acceptors or electrons
Why can't cells use the breakdown of glucose to pyruvate to generate energy without further conversion of pyruvate via fermentation or respiration?
The electron acceptor reduced (NADH) during glycolysis must be regenerated (NAD+)
intermediary metabolism
The entire set of cellular metabolic reactions
criteria to construct a metabolic pathway
The individual reactions must be specific. The pathway in total must be thermodynamically favorable. A thermodynamically unfavorable reaction in a pathway can be made to occur by coupling it to a more favorable reaction
aerobic glycolysis/Warburg effect
the ability for rapidly growing tumors to obtain ATP by metabolizing glucose to lactate even in the presence of oxygen
three ways homeostasis of metabolic processes is regulated
The amount of enzymes present - quantity can be regulated at level of gene transcription The catalytic activity of enzymes - regulated by allosterically or covalent modification. Hormones coordinate metabolic activity, often by instigating the covalent modification of allosteric enzymes. The accessibility of substrates.
NAD+ regeneration after glycolysis
- The conversion of glucose into pyruvate generates ATP, but for ATP synthesis to continue, NADH must be reoxidized to NAD+. This vital coenzyme is derived from the vitamin niacin (B3). - an energy converting pathway that stops at pyruvate will not proceed for very long because redox balance is not maintainted because most of the NAD+ in the cell has been reduced to NADH, so more NAD+ needs to be regenerated for glycolysis to proceed NAD+ can be regenerated by further oxidation of pyruvate to CO2, or by the formation of ethanol or lactate from pyruvate. reactiosn that include NADH can form ethanol or lactate (anaerobic/fermentations), or pyruvate can be couples to Coa to form acetyl CoA (aerobic) in catabolism the acetyl CoA product is then used as a substrate for the citric acid cycle in anabolism the acetyl CoA prduct is then used as a substrate to make fatty acids
Why are phosphate esters prominent in biology?
-Phosphate esters are thermodynamically unstable, yet they are kinetically stable. -Phosphate esters are stable because the inherent negative charges resist hydrolysis. -Because phosphate esters are kinetically stable, they are ideal regulatory molecules, added to molecules by kinases and removed by phosphatases.
glyceraldehyde 3-phosphate (G3P) dehydrogenase mechanism
1. G3P binds to enzyme's active site which contains NAD+ 2. the SH group of active site in Cys residue forms a covalent bond with G3P 3. NAD+ oxidizes substrate, forming a thioester intermediate 4. NADH exists and is replaced by another molecule of NAD+ and Pi enters active site 5. Pi attacks thioester, forming 1,3-biphosphoglycerate and regenerating enzyme
synthesis of acetyl CoA from pyruvate
1. decarboxylation 2. oxidation 3. transfer to CoA pyruvate dehydrogenase complex drives reaction
glycolysis: step 8-10
3-phosphglycerate converted into 2-phosphoglycerate by phosphoglycerate mutase 2-phosphoglycerate is then dehydrated by enolase, producing phosphoenolpyruvate (PEP) - has high phosphoric-transfer because phosphate traps compound in unstable enol tautomer (unstable so wants to get rid of phosphate) PEP phosphorylates ADP, generating ATP and pyruvate, reaction catalyzed by pyruvate kinase
number of ATP generated by oxidative phosphorylation
32 ATP generated per molecule of glucose
Carbon compounds that are oxidized to synthesize ATP
Carbon compounds are oxidized with a phosphate (PO4) to create a high phosphoryl-transfer potential intermediate so one oxygen can stay and oxidize the carbon and the PO3 leaves to attach to the ADP and form ATP the essence of catabolism - capturing the energy of carbon oxidation for ATP
CAC intermediate biosynthetic precursors
Citrate --> fatty acids and steroids a-ketoglutarate --> glutamate --> other aa --> purines succinyl CoA --> porphyrins, heme, chlorophyll oxoaloacetate --> glucose or aspartate --> other aa, purines, and pyrimidines
glycolysis: step 5
DHP (one of the two products) is converted to G3P (the other product) by triose phosphate isomerase so 2 G3Ps are produced
various means of generating ATP during exercise
Exercise is initially powered by existing high phosphoryl-transfer compounds (ATP and creatine phosphate). Subsequently, the ATP must be regenerated by metabolic pathways. - creatine phosphate can regenerate ATP from ADP, allowing a short burst of activity as in a sprint. - Once the creatine phosphate stores are depleted, ATP must be generated by metabolic pathways.
glycolysis: step 6
G3P is oxidized by glyceraldehyde 3-phosphate dehydrogenase to produce a high phosphoryl transfer potential compound, 1,3-biphosphoglycerate NAD+ is reduced to NADH then need to be reoxidized 1,3-biphosphyglycerate produced in 2 steps: 1. the highly exergonic oxidation of carbon 1 in G3P to 3-phosphoglycerate (carboxylic acid) 2. the highly endergonic formation of 1,3-biphosphoglycerate from 3-phosphoglycerate These two reaction are linked by the formation of an energy-rich thioester in the active site of glyceraldehyde 3-phosphate dehydrogenase
galactose matabolism
Galactose is converted into glucose 6-phosphate by the galactose-glucose conversion pathway, which begins with the phosphorylation of galactose by galactokinase. 1. galactose is phosphorylated by galactokinase, forming galactose 1-phosphate 2. galactose 1-phosphate reacts with activated glucose (UDP-glucose) to form UDP-galactose 3. UDP-galactose reacts with glucose 1-phosphate to form UDP-glucose and glucose 6-phosphate by phosphoglucomutase galactose is highly toxic if the transferase is missing - if galactose is converted in to galactitol, which is osmoticdally active, water diffuses into the lens causing a clouding in the lens, called cataracts
glycogen breakdown steps
Glycogen phosphorylase degrades glycogen from the nonreducing ends of the glycogen molecule (can only act on linear chains (α1-4 glycosidic linkage) The phosphorylase catalyzes a phosphorolysis reaction that yields glucose 1-phosphate. Glucose 1-phosphate is converted in glucose 6-phosphate by phosphoglucomutase and enters glycolysis at step 2 stops 4 residues away from α1-6 branch until it is debranched by debranching enzyme this process occurss to make glucose before gluconeogenesis kicks in a phosphorolysis - thermodynamically favorable
glycolysis: step 1
Hexokinase traps glucose in the cell and begins glycolysis Hexokinase, which requires Mg2+ or Mn2+ as a cofactor, catalyzes reaction of glucose being phosphorylated to form glucose 6-phosphate at the expense of ATP which destabilizes it Hexokinase, like most kinases, employs substrate-binding induced fit to minimize hydrolysis of ATP. first "committed" step now G6P cant leave cell because negative charge means it can't use the glucose transporter
Catabolic pathways
Metabolic pathways that combust carbon fuels to synthesize ATP - energy yielding reaction
anabolic pathways
Metabolic pathways that use ATP and reducing power to synthesize large biomolecules - energy requiring reactions
glycogen synthesis
UDP-glucose - monomer that is used to extend glycogen chain in synthesis, glucose donor synthesized by UDP-glucose pyrophosphorylase - irreversible by the hydrolysis of pyrophosphate a branching enzyme generates branches on glycogen by cleaving an α-1,4-linkage and takinga block of about 7 glucoses and synthesizing α-1,6-linkage so glycogen sythase can then extend the branched polymer
redox potential
a measure of a molecules tendency to donate or accept electrons - electron transfer potential a strong reducing agent readily donates e- and has a negative E0' a strong oxidizing agent readily accepts e- and has a positive E0' E0' effects ∆G FADH2 has a lower reduction potential than NADH so the electrons passed by FADH2 release less energy and generate less ATP than those passed by NADH
glycolysis: step 3
a second phosphate is added to fructose-6-phosphate to make fructose-1,6-biphosphate by phosphofructokinase (PFK) which traps the chain in this form rate-determining step of glycolysis pathway, slowest step regulation is important
metabolism
a series of linked reactions that convert a specific reactant to a specific product
Cori cycle
a series of sections that display inter-organ cooperation between the muscle and the liver lactate formed by the muscle is converted into glucose by the liver the glucose is then released into the blood to be supplied to the muscles for further glycolysis if muscle activity stops, the glucose is used to replenish the supplies of glycogen through glycogenesis indirectly moves ATP from liver to muscles
Citric acid cycle net reaction
acetyl CoA + 3NAD+ + FAD + ADP + Pi + 2H2O --> 2 CO2 + 3 NADH + FADH2 + ATP + H+ + CoA
citric acid cycle
also called TCA or Krebs cycle oxidizes the acetyl fragment of acetyl CoA to CO2 in the process of oxidation, high energy electrons are captured in the form of NADH and FADH2, which transfer chemical energy function of citric acid cycle is to harvest high-energy electrons from carbon fuels first two carbons are introduced into the cycle by condensation of oxaloacetate, an acetyl group with a 4 carbon compound forms citrate, a 6 carbon compound, which undergoes two oxidative decarboxylations, generating two molecules of CO2 in second stage, oxaloacetate is regenerated both stages generate high-energy elections (NADH and FADH2) that are used to power ATP synthesis in oxidative phosphorylation
Why are fats a more efficient food source than glucose?
because the carbons in fats are more reduced
hexokinase vs glucokinase
both isozymes hexokinase: saturated by glucose glucokinase: regulated by glucose (only needed after a meal when the blood glucose levels are high), found in liver and pancreatic B cells (where is signals insulin release), has a high Km so its reaction velocity changes in response to glucose conc (activity sensitive to changes in glucose conc between 4mM before meal and 8 mM after meal)
what are the electron donors and acceptors in lactic acid fermentation and alcoholic fermentation?
both oxidation-reduction reactions G3P is the electron donor in both in lactic acid fermentation pyruvate is the electron acceptor, converting to lactate in alcoholic fermentation, acetaldehyde is the electron acceptor, forming ethanol
Similarities and differences between NAD+ and FAD
both pick up 2 electrons: NAD+ picks up 1 H- and FAD picks up 2 H+ NAD+ is used for oxidation of C-O FAD is used for oxidation of C-C NAD+ is charged and FAD is neutral
fructose metabolism
can be converted to glycolytic intermediate in glycolysis can be directly phosphorylated by hexokinase and go into glycolysis metabolized by fructose 1-phosphate pathway in liver, where the key regulatory enzyme of glycolysis, phosphofructokinase, is by-passed Excess fructose consumption has been linked to obesity, fatty liver, and the development of type 2 diabetes.
amphibolic pathways
can function anabolically or catabolically
oxidative phosphorylation
captures energy of high energy electrons to synthesize ATP occurs in electron-transport chain where electrons flow from NADH and FADH2 to O2 and generates a proton gradient this proton gradient is used to power the synthesis of ATP the CAC + oxidative phosphorylation are called the cellular respiration cycle
succinyl CoA synthetase
catalyzes cleavage of thirster linkage and forms ATP cleavage of thioester of succinyl CoA powers formation of ATP - example of substrate level phosphorylation forms succinate - a symmetric molecule so the identity of the carmon atoms from the acetyl unit is lost, "scrambles" the new carbons so the CoA could be in any of the 4 carbons of fumarate formed no carbons of acetyl CoA will be released as CO2 in the first round, but may be released in following rounds
Citrate synthase
catalyzes condensation of acetyl CoA and oxaloacetate to form citrate in first stage of cellular respiration (citric acid cycle) exhibits induced fit - oxaloaceetate binding by citrate synthase induces structural changes that lead to the formation of the acetyl CoA binding site the formation of the intermediate citryl CoA causes another structural change which completes the formation of the active site citryl CoA is cleaved for form citrate and coenzyme A - irreversible step, highly exergonic/favorable
aconitase
catalyzes formation of isocitrate from citrate in citric acid cycle
isocitrate dehydrogenase
catalyzes oxidative decarboxylation of isocitrate, forming a-ketoglutarate and capturing high energy electrons as NADH in citric acid cycle NAD+ is oxidizing agent CO2 is released
a-ketoglutarate dehydrogenase
catalyzes synthesis of succinyl CoA from a-ketoglutarate in citric acid cycle generates NADH and second CO2 released (2 carbon go in as acetyl CoA and are lost at CO2) structurally and mechanistically similar to pyruvate dehydrogenase complex
Electron Transport Chain
composed of 4 large protein complexes through which the electrons donated from NADH and FADH2 are passed to electron carriers electrons flow from NADH to O2 through Complex I, Complex III, and complex IV, all embedded in the inner mitochondria - pump protons out of the mitochondria, generating a proton gradient Complex II delivers electrons from FADH2 to Complex III succinate dehydrogenase is part of Complex II electron affinity of the components increases as electrons move down the chain electrons move from matrix to the intermembrane space
glycolysis
converts one molecule of glucose to 2 molecules of pyruvate with the generation of 2 molecules of ATP 2 stages: stage 1 (steps 1-5) - traps glucose in the cell and modifies it so that it can be cleaved into a pair of phosphorylated 3-carbon compounds (PO4 is added), "energy investment", 2 ATP per glucose needed stage 2 (steps 6-10) - oxidizes the 3-carbon compounds to pyruvate while generating 2 molecules of ATP (each releases PO3 to add to ADP to produce ATP), "energy payoff", produces 4 ATP because happens twice whole process produces a net of 2 ATP (2 used and 4 produced) and 2 NADH
gluconeogenic pathway
converts pyruvate into glucose (reverse glycolysis), the synthesis of glucose from noncarbohydrate percursors, occurs when glucose is low pyruvate can be formed from muscle-derived lactate in liver from lactate dehydrogenase The carbon skeletons of some amino acids can be converted into gluconeogenic intermediates. glycerol, derived from the hydrolysis of triacylglycerols, can be converted into dihydroxyacetone phosphate, which can be processed by gluconeogenesis or glycolysis 3 irreversible steps in glycolysis must be bypasses in gluconeogenesis (1,3,10)
Acetyl CoA
derived from fats and carbohydrates CoA is an activated carrier of acetyl groups CoA takes acetyl group in order to create acetyl CoA - the vitamin that starts the cellular energy cycle high energy because less resonance stabilization the transfer of the acetyl group is exergonic because the thiester is unstable (S is a good leaving group) hydrolysis of acetyl CoA is energetically favorable can drive transfer of 2 carbon units, will have to put in energy to create acetyl CoA
transport shuttles of the mitochondrial membrane
electrons from NADH enter the mitochondrial ETC by dihydroxyacetone phosphate being reduced to G3P, electrons are transfered to FAD in the G3P dehydrogenase, which membrane bound, and G3P is reoxidized another transfer of electrons to Q forms QH2, allowing the electrons to enter the ETC
futile cycles
energy waste compartmentation and allosteric control of anabolic and catabolic processes prevent this
control sites in metabolic pathways
enzymes catalyzing irreversible reactions hexokinase, phosphofructokinase, and pyruvate kinase in glycolysis - hexokinase - catalyzes the first step in glycolysis, inhibited by its produce glucose 6-phosphate, high concentrations of glucose 6-phosphate signal that the cell no longer requires glucose for energy so no more glucose is broken down - phosphofructokinase - most important control site in mammals, produces fructose 1,6-biphosphate from fructose 6-phosphate, allosterically inhibited by high levels of ATP, ATP binds to specific regulatory site which lowers the enzymes affinity for fructose 6-phosphate, AMP reverses the inhibitory action of ATP because it also binds to the same binding site in the enzyme as ATP but doesnt lower the affinity so the activity of the enzyme increases (moer fructose 1,6-biphosphate is produced) when the ATP/AMP ratio is low (more AMP than ATP), when ATP needs are great adnylate kinase generates ATP from 2ADP and AMP becomes signal for low energy state ADP + ADP --> ATP + AMP - pyruvate kinase - yields ATP and pyruvate, allosterically inhibited by ATP and alanine and decreases rate of glycolysis when energy charge of cell is high (there is a lot of ATP), stimulated by fructose 1,6-biphosphate, product of phosphofructokinase, so when there is a lot of fructose 1,6-biphosphate the enzyme activity is high alanine is made in one step from pyruvate and signals the abundance of building blocks. in muscle, glycolysis is regulated to meet the energy needs of contraction.
hydrolysis of ATP is endergonic or exergonic?
exergonic because the triphosphate unit contains two phosphoanhydride bonds that are unstable The energy released on ATP hydrolysis is used to power a host of cellular functions ATP hydrolysis drives metabolism by shifting the equilibrium of coupled reations - can turn endergonic reactions exergonic
cellular respiration
first stage: citric acid cycle - the removal of high-energy electrons from carbon fuels second stage: oxidative phosphorylation - these electrons reduce O2 to generate a proton gradient which is used to synthesis ATP
F-2,6-BP
fructose 2,6-bisphosphate - regulates gluconeogenesis pathways, key regulator for whether glycolysis or gluconeogenesis is favored synthesized by phosphorylation of F6P using ATP by phosphofructokinase 2 F2,6BP is an activator of phosphofructokinase 1 in glycolysis and an inhibitor of fructose-1,6-bisphosphatase in gluconeogenesis
glycolysis: step 4
fructose-1,6-biphosphate is split into two 3 carbon chains (DHAP and GAP/G3P) by aldolase uses covalent cataysis and acid-base catalysis thermodynamically unfavored byt pushed forward by Le Chatelier's principle: as products are made, they are quickly consumed by downstream enzymes
glycolysis reaction
glucose + 2NAD+ + 2ADP + 2Pi --> 2 pyruvate +2NADH + 2ATP
glucose metabolism
glucose is metabolized by glycolysis to pyruvate in 10 steps. That pyruvate is then metabolized to lactate under anaerobic conditions, and acetyl CoA under aerobic conditions. Acetyl CoA are oxidized to CO2
glycolysis: step 2
glucose-6-phosphate is converted to fructose-6-phosphate by phosphoglucose isomerase reaction is reversible - direction only controlled by concentration of products and reactants
regulation of glycogen breakdown
glycogen degration is stimulated by epinephrine or glucagon binding to 7TM receptors epinephrine - stimulates glycogenolysis to power contraction in muscles during "fight or flight" glucagon - stimulates glycogen breakdown in liver when blood glucose is low both activate adenylate cyclase --> cAMP --. activates protein kinase A
which enzymes in glycolysis catalyze irreversible reactions
hexokinase, phosphofructokinase, and pyruvate kinds because have large negative ∆G (very favorable reactions) drive reaction - points of regulation hexokinase (step 1) cant be only point of regulation because starts as disaccharide and monosaccharides are needed to feed into glycolysis pyruvate kinase (step 10) is second control point and can have feed-forward regulation by FBP
enzymes in the liver
hexokinase: allosteric enzyme in liver as it is in muscle pyruvate kinase: regulated allosterically in liver as it is in muscle, but also regulated by covalent modification in liver where low blood glucose leads to phosphorylation and inhibition of liver pyruvate kinase (if glucose levels are low there isn't much for pyruvate kinase to synthesize ATP with so pyruvate kinase in inhibited cause its not needed) glucokinase (hexokinase IV): enzyme primarily responsible for phosphorylating glucose in liver, active only after a mean when blood glucose levels are high (after a mean there is a lot of glucose that can be phosphorylated and converted to ATP) GLUT1-5: glucose transporters that facilitate the movement of glucose across the cell membrane
glucose 6-phosphatase in the liver
hydrolized to generate free glucose in the liver to release into the blood to be used by other tissues such as the brain and red blood cells absent in most other tissues Other tissues that store glycogen such as muscle lack glucose 6-phosphatase and break down glycogen only for their own needs
fructose metabolism in adipose tissue vs liver tissue
in adipose tissue enters glycolysis when fructose is converted to fructose-6-phosphate in liver tissue enters glycolysis when fructose is converted to fructose-1-phosphate
Why does it make good physiological sense for insulin to increase the number of glucose transporters in the cell membrane?
insulin indicated the fed state, meaning an increase in blood glucose levels after a meal, so insulin leads to the removal of glucose from the blood for storage or metabolism (energy) and increasing the number of transporters makes this process more efficient because it increases the amount of glucose crossing into the cell (transporters have binding sites for insulin)
insulin release
insulin is secreted by B cells in pancreas as a response to a signal from gulcokinase when glucose blood levels are high (stimulated by metabolism of glucose by B cells) glucose enters B cells through glucose transporters GLUT2 and metabolized to pyruvate which is oxidized to CO2 and H2O ATP is released and increase in ATP closes K+ channel (channel through which K+ exits cell) which alters charge across cell and opens Ca2+ channels which stimulates release of insulin
mitochondria and oxidative phosphorylation
inter membrane space is where the ETC and ATP synthesis occur in inter membrane space CAC and fatty acid oxidation occur in matrix
aerobic metabolism in the mitochondria
involving oxygen pyruvate enters mitochondria where it is converted into acetyl CoA the pyruvate dehydrogenase complex, a mitochondrial complex enzyme, oxidatively decarboxylates pyruvate to form acetyl CoA, a reaction that is an irreversible link between glycolysis and the citric acid cycle the acetyl CoA is the fuel for the citric acid cycle which converts the acetyl CoA into 2 molecules of CO2 and ATP total production of 2 ATP and 4 NADH pyruvate + CoA + NAD+ --> acetyl CoA + CO2 + NADH + H+ fatty act degradation is also an important source of acetyl CoA for the citric acid cycle acetyl CoA is either metabolized by the citric acid cycle or incorporated into fatty acids
control points of CAC
irreversible reactions (1,3,4) - citrate synthase, isocitrate dehydrogenase, and a-ketoglutarate dehydrogenase citrate synthase recieves feedback inhibition from succinyl CoA, ATP, and NADH pyruvate dehydrogenase controls the entry of acetyl CoA (derived from pyruvate) into the cycle
entry points into gluconeogenesis
lactate and some amino acids enter at pyruvate, some amino acids enter at oxaloaceate, and glycerol enters at DHAP which is converted to G3P
ATP synthase
made of an F1 and an F0 component F1 - contains active sites and protrudes into the mitochondrial matrix, active sites located on 3 B subunits F0 - embedded in inner mitochondrial membrane and contains proton channel y subunit connects F1 and F0 each B subunit interacts differently with y subunit
activated carriers
molecules that temporarily carry a group so it can be transferred must be: kinetically stable in the absence of specific catalysts and the metabolism of activated groups is accomplished with a small number of carriers ATP is an activated carrier of phosphoryl groups NAD+ - an active carrier of high-energy electrons and is reduced to NADH - used for ATP generation NADP+ - an activated carrier of electrons for biosynthesis CoA - activated carrier of acyl groups such as the acetyl group, transfer of acyl group is exergonic because thioester is unstable
second phase of pentose phosphate pathway
non oxidative introversion of phosphorylated sugars
chemotrophs
obtain energy through the oxidation of carbon fuels
obligate anaerobes
organisms that that cannot survive in the presence of oxygen some are pathogenic (disease causing) Skeletal muscles in most organisms can function anaerobically for a short period of time, resulting in the build-up of lactate. It is much more energetically favorable to use aerobic metabolism/oxidative phosphorylation.
energy source used to regenerate ATP from ADP and Pi
oxidation of carbon to CO2 oxidation is a loss of electrons and the electrons released from converting C to CO2 (or O to H2O) is used as energy to convert ADP and Pi to ATP
oxidation-reduction reaction/redox reactions
oxidation reactions (loss of electrons) coupled with reduction reactions (gain of electrons) The carbon atoms in fuels are oxidized to yield CO2, and the electrons are ultimately accepted by oxygen to form H2O The more reduced a carbon atom is, the more free energy is released upon oxidation
First phase of pentose-phosphate pathway
oxidative generation of NADPH, a key product of the pentose pathway and the source of biosynthetic reducing power glucose 6-phosphate dehydrogenase initiates the oxidative phase with the conversion of glucose 6-phosphate into 6-phosphoglucono-G-lactone in the process, G6P dehydrogenase reduces NADP+ to NADPH irriversible step and control point, controleld by NADP+/NADPH ratio second NADPH generated when 6-phosphoglucono-G-lactone is converted to ribulose 5-phosphate and CO2 glucose 6-phosphate + HADP+ + H20 --> ribulose 5-phosphate + 2 NADPH + 2H+ + CO2
bypassing first two irreversible steps in glycolysis
pyruvate is converted to oxaloacetate by pyruvate carboxylase oxaloacetate is converted to phosphoenolpyruvate by phosphoenolpyruvate carboxykinase
anapleaurotic reactions
reactions that replenish the CAC, required if the energy status of the cell changes catalyzed by pyruvate carboxylase also used in gluconeogenesis and dependent on presence of acetyl CoA replenishes oxaloacetate from pyruvate
regeneration of oxaloacetate
regenerated by the oxidation of succinate through succinate dehydrogenase, fumarase, and malate dehydrogenase succinate dehydrogenase is the ony enxzyme in the CAC embeded in the mitochondrial membrane succinate dehydrogenase and fumerase are reversible malate has a positive ∆G so needs to be driven forward by use of oxaloactate in next reaction (citrate synthase)
aldolase mechanism
splits fructose-1,6-biphosphate into two 3 carbon chains 1. linear fructose-1,6-biphosphate binds to enzyme 2. active site Lys residue in aldolase reacts with carbonyl group in F-1,6-BP to form a Schiff base (covalent catalysis) 3. Tyr side chain in aldolase acts as base (N gives up electrons to break pi-bond) and accepts proton from F-1,6-BP, breaking bond between C3 and C4 which produces an aldehyde, facilitated by protonated Schiff base because its a better electron-withdrawing group than at the carbonyl group that was at C2 4. Tyr residue gives up its proton to the F-1,6-BP, reforming the Schiff base 5. Schiff is hydrolyzed, releasign the second product and regenerating aldolase
insulin in glycogen synthesis
stimulates glycogen synthesis by activating a signal transduction pathway that results in the phosphorylation and inactivation of glycogen synthase kinase thenprotein phosphatase 1 (PP1) removes the phosphoryl groups (dephosphorylates) from glycogen synthase, generating the active a form of the synthase and allowing glycogen synthesis insulin also facilitates glycogen synthesis by increasing the number of GLUT4 in the membrane regulated by allosteric regulation of glycogen synthase and glycogen phosphorylase glycogen synthase activated by G6P (shows a lot of energy/ATP) glycogen phosphorylase is activated by AMP and inhibited by ATP
insulin kinase cascade (insulin signaling)
the binding of insulin causes the cross-phosphorylation and activation of the insulin receptor kinase. the activated kinase of the insulin receptor phosphorylates insulin-receptor substrates (IRSs) which are adaptor proteins that signal insulin, this sets off a cascade of kindness and second messenger phosphatidylinositol 3,4,4-triphosphate (PIP3) which ends in the activation of AKT kinase which phosphorylates the GLUT4, increasing glucose uptake by cells (glucose travels with its concentration gradient into the cell, removing glucose from the blood) and the enzymes that convert glucose to glycogen (for storage)
alcoholic fermentation
the conversion of glucose into 2 molecules of ethanol alcohol dehydrogenase oxidizes NADH, regenerating NAD+, and generatees ethanol glucose + 2Pi + 2ADP + 2H+ --> 2 ethanol + 2CO2 + 2ATP + 2H20
lactic acid fermentation
the conversion of glucose into 2 molecules of lactate NADH is oxidized by converting pyruvate to lactate, reaction catalyzed by lactate dehydrygenase glucose + 2Pi + 2ADP --> 2 lactate + 2ATP + 2H20
how many ATP do NADH and FADH2 generate
the electrons from NADH will generate 2.5 ATP and FADH2 will power synthesis of 1.5 ATP both with the reduction of oxygen in the ETC
glycolysis: step 7
the energy of oxidizing the carbon atom to form 1,3-biphosphoglycerate is used to form ATP because 1,3-biphosphoglycerate has a greater phosphoric transfer potential than ATP and can be used to power the synthesis of ATP from ADP and Pi in a reaction catalyzed by phosphoglycerate kinase 1,3-BPG has great phosphoryl transfer potential so it transfers its acyl-phosphate to ATP and produces 3-phosphoglycerate again (1,3-BPG was only formed in order to transfer acyl-phosphate to ATP) each G3P produces an ATP so 2 ATPs are produced because started with 2 G3P)
Phosphoryl-transfer potential
the standard free energy of hydrolysis― a means of comparing the tendency of organic molecules to transfer a phosphoryl group to an acceptor molecule - an important form of cellular energy transformation ATP has a phosphoryl-transfer potential intermediate between high phosphoryl- potential compounds derived from fuel molecules and acceptor molecules that require the addition of a phosphoryl group for cellular needs. ATP has a high phosphoryl-transfer potential because of four key factors: charge repulsion is reduced when phosphoryl group is removed products of ATP have more resonance stabilization than ATP increase in entropy when one molecule of ATP --> ADP + Pi stabilization by hydration - products of hydrolysis are more effectively stabilized by association with water than is ATP high phosphoryl-transfer-potatial compounds are used to power ATP synthesis and ATP donates a phosphoryl group to other biomolecules to facilitate their metabolism
how ADP is the major regulator of cellular respiration
the synthesis of ATP from ADP to Pi controls the flow of electrons from NADH and FADH2 to oxygen, and the availability of NAD+ and FAD after this transfer of electrons has been made controls the rate of the CAC electrons are only transferred to O2 if ADP is constantly phosphorylated to ATP, so the rate of O2 consumption increases when ADP is added cause that means more ATP can be synthesized
what is the purpose of phosphorylating glucose in cytosol?
to trap glucose in the cell and destabilize glucose and facilitate the next series of metabolic steps (glycolysis step 1)
type 1 vs type 2 diabetes
type 1: deficiency in cells that produce insulin, autoimmune disease where beta cells are destroyed so no insulin is produced (B cells are cells in pancreas which release insulin based on high glucose levels in blood) type 2: deficiency in response to insulin, body makes insulin but there is insulin resistance no glucose transported into cells = hyperglycemia cells respond as if no glucose is precent = gluconegenesis, exacerbates hyperglycemia