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46 Cards in this Set
- Front
- Back
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yes
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no
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synthase
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catalyzes condensation reactions, build new bonds
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synthetase
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consendation reactions requiring ATP as an acceptor
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kinase
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catalyzes phosphorylation reactions to transfer a phosphoryl group from ATP
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dehydrogenase
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removal a pair of hydrogen atoms
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phosphatase
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dephosphorylation
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phosphorylase
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phosphorolytic reactions
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2 phases of Glycolysis
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1. Preparatory phase: investment of 2 ATP and splitting of glucose
2. Payoff phase: yield, oxidoreduction-phosphorylation stage |
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3 regulatory enzymes that act as "valves" that control the rate of glycolysis and preserve homeostasis
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1. hexokinase (step one)
2. Phosphofructokinase-1 (step 3) 3. Pyruvate kinase (step 10) |
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Glycolytic enzyme mnemonic
10 enzymes in order |
Hungry Peter Pan And The Growling Pink Panther Eats Pies
H: Hexokinase P: phosphohexo isomerase P: Phosphofructokinase-1 (AKA 6-phosphfructo-1 kinase) A: Aldolase T: Triose phosphate isomerase G: glyceraldehyde 3-phosphate dehydrogenase P: phosphoglycerate kinase P: phosphoglycerate mutase E: enolase P: pyruvate kinase |
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Glycolysis step 1
preparatory phase |
Substrate: glucose
enzyme: hexokinase product: glucose-6-P phosphorylation "traps" glucose in the cell, commits it to glycolysis |
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glycolysis step 2
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S: glucose-6-P
E: phosphexo isomerase P: Fructose-6-P |
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Glycolysis step 3
preparatory phase |
S: Fructose-6-P
E: phosphofructokinase-1 (AKA 6-phosphofructose-1-kinase) MAJOR regulatory enzyme of glycolysis** P: Fructose 1,6-bisphosphate |
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Glycolysis step 4
preparatory phase |
Splitting step
S: Fructose-1,6-bisphosphate E: Aldolase (aldol condensation) P: Dihydroxyacetone phosphate AND glyceraldehyde-3-Phosphate (2 3 carbon products) reversible rxn, but driven in direction to Glyceraldehyde 3-P in step 6 |
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Glycolysis step 5
preparatory phase |
S: dihydroxyacetone P
E: triose phosphate isomerase P: Glyceraldehyde 3-P |
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Glycolysis step 6
payoff phase |
P: glyceraldehyde 3-P and Pi
E: glyceraldehyde 3-P dehydrogenase (sulfhydral group in enzyme binds covalently to intermediate thiohemiacetal, converts to tioester and NAD+ reduced, then acyl transfer to form product of this step.. Poisons like mercury/heavy metals) can inhibit this binding***) P: 1,3-bisphosphoglycerate Loss of H, and convert NAD+ to NADH (2 total) |
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CC: mercury and alkylating agents (heavy metals)
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Mercury and alkylating reagents (iodoacetate) bind to sulfhydryl goup in active site of glyceraldehyde 3-P dehydrogenase (step 6 glycolysis)
-thiohemiacetal with glyceraldehyde 3-P cannot form and glycolysis stops -heavy metal prevents intermediate from binding to the enzyme |
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Glycolysis step 7
payoff phase |
S: 1,3-bisphosphoglycerate and ADP
E: phosphglycerate kinase, Mg2+ P: 3-phosphoglycerate 2 ATP generated enzyme named for reverse reaction, actually removal of a phosphate Glyceraldehyde 3-phosphate dehydrogenase and phosphoglycerate kinase are complexed together for faster passing the intermediate |
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Glycolysis steps 6 and 7
Affect of Arsenate |
arsenate resembles Pi and can substitue for it in the glyceraldehyde 3P dehydrogenase rxn
-phosphoglycerate kinase rxn (step 7) is bypassed, 3-phosphoglycerate is still formed and glycolysis continues but ATP not produced, no net ATP |
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Glycolysis step 8
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S: 3-phosphoglycerate
E: phosphoglycerate mutase P: 2-phosphglycerate |
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glycolysis step 9
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S: 2-phosphoglycerate
E: enolase (dehydration rxn) P: phosphoenolpyruvate **site of fluoride poisoning Also step where glc level for diabetes diagnosis is measured (need to test blood b4 completion of glycolysis. Test contains fluoride to prevent enolase activity to preserve glc) |
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Glycolysis step 10
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S: phosphoenolpyruvate and ADP
E: pyruvate kinase (Mg, K) P: pyruvate and 2 ATP E named for reverse rxn PEP forms enol, converted to final keto form of pyruvate **keto pyruvate is stabilized relative to PEP. Reaction CANNOT go in reverse -pyruvate kinase inhibited by ATP, acetyl CoA, and long chain fatty acids -deficiency of pyruvate kinase= hemolytic anemia |
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Glycolysis scorecard
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Before: 1 glucose, 2 ATP, 2 NAD+, 4 ADP, 2 Pi
After: 2 pyruvate, 4 ATP, 2 NADH, 2 ADP, 2 H+, 2 H2O |
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Glycolysis: Anaerobic Conditions
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lactic acid made to regenerate NAD+
-catalyzed by lactate dehydrogenase -"burn" muscles start making lactic acid instead of pyruvate, muscles litterally burning dure to lowering of pH |
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Clinical correlation: lactic acidosis
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CC: elevated blood lactate levels, decreased blood pH and bicarbonate levels, overproduction/underutilization of lactate, normal increase in lactate production when O2 supply is low
-decrease in ATP b/c less OP= increase phosphfructokinase-1 activity (glycolysis ATP production) -lactate is either combusted to CO2 and water or converted back to glucose (both require oxygen) -decreased lactate utilization: liver disease, ethanol, drugs like phenformin (former treatment for hyerglycemia, inhibits complex I of ETC to cause lactic acidosis) -thiamin deficiency: loss of activity of Pyruvate dehydrogenase complex, poorly nurished alcoholics |
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Anaerobic glycolysis in yeast
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pyruvate converted to acetaldehyde by pyruvate decarboxylase (CO2 lost). Then alcohol dehydrogenase reduces acetaldehyde to ethanol, NADH oxidized
*BEER* |
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Regulation of glc
major functions of liver and muscle |
Liver: long-term glycogen storage or export of Glc to blood to maintain levels and to make energy, gluconeogenesis essential to maintaining blood glc levels
Muscle: USES glc for energy production or short-term storage *rate of glycolysis is controlled differently in different tissues, glycolysis occurs in anaerobic and aerobic conditions |
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Regulatory enzymes:
Hexokinase allosteric inhibitor isozyme in liver |
-inhibited allosterically by G6P
-isozymes of hexokinase= different enzymes in different tissues that catalyze same rxn -isozymes: ability to regulate rxn based on needs of the tissues -Liver: glucokinase isozyme= lower activity than hexokinase in skeletal muscle, subject to additional regulatory mechanisms, and can be translocated to nucleus where it is inactivated by binding with GK-Regulatory Protein to further regulate glycolysis in liver (shunted away from cytosol so it doesnt enter glycolysis) |
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Regulation enzymes:
Pyruvate kinase |
-enzyme is allosterically inhibited by ATP, aceytl CoA (downstream products), and long chain fatty acids
-isozymes exist -hepatic (liver) pyruvate kinase is ***INactivated by phosphorylation (pyruvate kinase B) |
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Regulation enyzmes:
phosphofructokinase-1 |
conversion of fructose-6-P and ATP to Fructose 1,6-bisphosphate and ADP
-deaccelerated by ATP and Citrate *ATP is an allosteric inhibitor, feedback mechanism -accelerated by AMP,ADP, and fructose 2,6-bisphosphate *F2,6-bP= allosteric activator, derivitive of F6-P** (NOT 1,6bP), made by 6-phosphofructo-2-kinase (makes)/fructose 2,6-bisphosphatase (makes fructose-6-P) |
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Regulation rxn: F-2,6-bP
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Phosphofructokinase-2 and F-2,6-bisphosphotase located on same polypeptide
-regulated by covalent modification activates phosphofructokinase-1 to convert fructose6P to Fructose 1,6-bisphosphate **major regulatory step of glycolysis |
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Hormonal regulation of glycolysis:
Glucagon in liver |
Glucagon: picks up low Glc signal, deccelarate glycolysis
secreted by pancreas liver is main target tissue decreases F26bP levels decreases glycolysis and glycogen synthesis increases gluconeogenesis and glycogen degradation leads to accumulation and export of glucose In liver: inhibition of glycolysis, glucagon increases cAMP--> activates PKA--> PKA activates/phosphorylates F-2,6-bisphosphatase--> F-2,6bP decreases= glycolysis inhibited |
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Hormonal regulation of glycolysis:
Epinephrine in 1. liver and 2. muscle |
Epi= signals muscles to make energy to move
muscle is primary target (can target liver) in muscle: stimulates glycogen degradation to glc and increases F26bP levels= increase glycolysis In liver: glycogen degradation to glc decreases F26bP levels= decreases glycolysis and increases gluconeogenesis 1. In liver: epinephrine acts just as glucagon does in liver 2. In cardiac muscle: eprinephrine accelerates glycolysis. Isozyme of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase -Epi increases cAMP--> cAMP activates PKa--> *PKa activates 6-phosphofructo-2-kinase (difference from Epi affect in the liver)--> Fructose 2,6-bisP levels increase= glycolysis accelerated |
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glycolysis in erythrocytes
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RBC depends on glycolysis for energy..no Krebs, no organelles
-feeds Glucose 6P can make pentose phosphates or lactate -lactate and H leave RBC |
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glycolysis in brain
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requires 120g glc/day: large amount of energy required
-glycolysis feeds into Krebs and OP -pentose phosphates made from glc 6P |
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Other roles of glycolysis: intermediates of other pathways
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Intermediates of energy conservation:
-aerobic: ATP and NADH -anaerobic: ATP G6P: precoursor to glycogen biosynthesis and nucleic acid synth glyceraldehyde 3P and pyruate: precursors for lipid biosynthesis pyruvate: precursor for AA biosythesis (and lipid biosynthesis) |
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Regulation of glycolysis: insulin in the liver and muscle
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Insulin recognizes high Glc, signal to stop making glc
1. In liver: insulin decreases cAMP and inhibits PKa -activates phosphoprotein phosphatase--> PPP activates 6-phosphofructose 2-kinase (deactivate phosphotase)--> fructose2,6-bisP levels increase..glycolysis accelerated in liver (**phosphorylation=activation) -increases glycolysis and glycogen synthesis -decreases gluconeogenesis and glycogen degradation 2. In muscle: insulin increases glc entry into cells, increases glycogen synthesis All leads to reduction in glc conc. |
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Clinical correlation: alcohol and barbituates
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-alcohol intoxication is synergistic and increases senstitivity to barbituates
-combo could be lethal -ethanol inhibits metabolism of barbituates: inhibits hydroxylation of barbituates by the NADPH-dependent cytochrome p450 system of ER in liver -no excretion of barb. by kidney and bile, stays in body= increased CNS depression -sober alcoholic is less sensitive to barbituates but combo of alcohol and barbituates still as dangerous |
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Clinical correlation: arsenic poisoning
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-Arsenite: trivalent, more toxic than arsenate, forms stable complex with enzyme bound to lipoic acid: pyruvate dehydrogenase, alpha-ketogluterate
-arsenate: pentavalent, less ATP producted b/c it substitues for Pi on enzymes forming unstable arsenate esters; competes with Pi and binds to G3P dehydrogenase, glycolysis continues directly to 3-phosphoglycerate, bypassing 1,3-phosphoglycerate intermediate which makes ATP when converted to 3-phosphoglycerate, glycolysis continues but No net ATP is produced |
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Clinical correlation: fructose intolerance
deficiency result/effects |
-due to deficency in liver enzyme aldolase B that splits fructose 1,6-bis-P into dihydroxyacetone phosphate and glyceraldehyde (step 4 of glycolysis).
-consumption of fructose= accumulation of F1P and depletion of Pi and ATP in liver -depletion of Pi= liver mitochondria cannot generate ATP by OP..ATP levels fall..liver cannot do its normal functions. -liver damage due to inability to mainatain normal ion gradients by the ATP-dependent pumps. cells swell= osmotic lysis -normal humans also have limited capacity to handle fructose -excessive fructose can deplete Pi and ATP |
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Clinical correlation: diabetes mellitus
Oral glucose tolerance test |
-derangements in carbs, fat, and protein metabolism
-oral glucose tolerance test for people without fasting hyperglycemia -after 2 hrs of eating, normally blood glc levels return to normal, but with the disease they stay elevated longer -stress, recent high carb consumption, and infection can mess up test -glc uptake by muscle and adipose is decreased due to lack of insulin or insulin resistance= GLUT4 transporter not moving glc into cells from blood (hyperglycemia) -liver parenchymal cells do not require insulin for glc uptake, but has diminished capacity to remove glc from blood w/o insulin -decreased glucokinase activity and other enyzmes of glycogenesis and glycolytic pathway |
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Clinical correlation: pickled pigs and malignant hyperthermia
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-sarcoplasmic reticulum has abnormal ryanodine receptor, a Ca2+ release channel
Taking HALOTHANE (anesthetic) causes dramatic rise in temperature, metabolic and respiratory acidosis, hyperkalemia, and muscle rigidity by causing excess Ca release and uncontrolled stimulation of myosin ATPase, glycogenolysis, glycolysis, and cyclic uptake and release of Ca2+ by mitochondria and SR -permenant damage to muscles from overheating, lactic acidosis, and ATP loss -skeletal muscles generate heat and lactic acid -dominantly inherited abnormality, death may occur at first exposure -death may not occur with icepacking and danthrolene for anti-acidosis -occurs in pigs= porcine stress syndrome, pale watery very low pH of meat= almost pickled |
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clinical correlation: Angina pectoris and myocardial infarction
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"strangling pain in the chest"
-due to imbalance b/t demand for and supply of blood flow to cardiac muscles -caused by narrowing arteries by artherosclorosis or spasm, blod clots commonly form -radiating pain/pressure in shoulder, arm, jaw, neck -treated: nitroglcerin/nitrates to relieve pain, causes dialation of arteries, improve O2 delivery and washes out lactic acid., produces NO that relaxes smooth muscle and reduces energy requirement of heart pumping and lowers oxygen requirement -calcium channel blockers and B-adrenergic blockers= prevent myocardial O2 increase induced by stimulation of Sympathetic NS (exercise). -coronary artery bipass is last resort |
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clinical correlation: pyruvate kinase deficiency and hemolytic anemia
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-anemia due to excessive RBC destruction
-most commonly caused by pyruvate kinase deficiency= lower ATP conc. in RBC -ATP needed for Na/K ion pumps, maintains shape of RBC, essential to function -pyruvate and lactate conc. decreases -BPG increases: decreased Hb affinity -Normal ATP levels in reticulocytes b/c they have mitochondria and can make ATP via OP -RBC depend soley on glycolysis= loss of mature cells from circulation |
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clinical correlation: hypoglycemia and premature infants
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-neonate brain is almost completely dependent on glc from liver glycogenolysis and gluconeogenesis
-premature's have smaller glycogen stores -PEP carboxykinase levels are very low few hrs after birth= limits glucose synthesis from lactate and alanine in the liver -newborns have limited capacity for ketogenesis= long-chain fatty acid transport into liver mitochondria is poorly developed, limited use of ketone bodies -also they have larger brain/body ratio and brain requires a greater amount of glc then rest of body |
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Clinical correlation: hypoglycemia and alcohol intoxication
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-intoxication in undernurished person or after strenous exercise can cause hypoglycemia
-inhibits hepatic gluconeogenesis -liver cannot handle reducing biproducts of ethanol oxidation fast enough= blocks conversion of lactose to glc, and promotes conversion of Ala to lactate=> lactate accumulation in blood -inox. can affect children and insulin-treated diabetics more severly |
