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17,18,19
why is glucose important
good fuel, builds carbonskeletons
what can glucose build the carbon skeletons of
amino acids, lipids, nucleotides, cofactors
the first stage of glucose metabolism
• a sequence of enzyme-catalyzed reaction by which glucose is converted into pyruvate
• In the process, some of the free energy is captured by the synthesis of ATP and NADH
glycolysis
in glycolosis One molecule of glucose is converted to , which gives rise to two molecules of pyruvate
fructose-1,6- bisphosphate
true or false: for all the reactions of glycolysis, there is a requirement for O2!
false
what are the three fates of pyruvate after it is formed
anaerobic glycolysis, aerobic oxidation, anaerobic alcoholic oxidation
what does the presence of o2 determine for pyruvate
wheter it enters the citric acid cycle
list the aerobic conditions
need oxygen, citric acid cycle, over 30 atp per glucose molecule, co2 h2o byprducts, occurs in mitochondria
list the anerobic conditions
oxygen not required, makes lactate (animals) ethanol (yeast), 2 atp per glucose, byproducts lactate (animals) co2 ethanol (yeast), occurs in cytoplasm in cells with low o2
______ respiration dominates during normal activity
aerobic
every glucose yields…
2 atp and 2 pyruvate
for the glycolosis reaction we must supply 2 _____
ATP
what are the 2 phases of glycolosis
priming phase and payoff phase
what happens in the priming phase
2 atp consumed, glucose phosphorylated and makes FBP, fbp split to make 2 g3p
what happens in the payoff phase
2g3p converted to pyruvate, 4 atp and 2 NADH produced
what are the 10 steps of glycolosis (Pretty Iguanas Punch Cats; Intelligent Owls Teach Idiots Difficult Tricks)
phosphorylation, isomerization, phosphorylation, cleavage, isomerization, oxidation, transfer, isomerization, dehydration, transfer
What happens in step 1 of glycolosis (phosphorylation)
phosphorylation of glucose with atp creates glucose-6-phosphate
which hexokinases are invloved in step 1 of glycolosis
I and IV
found in many tissues (brain, muscle, white blood cells)
• High affinity for glucose (low Km)
• Hill Coefficient = 1
• Regulated by allosteric feedback inhibition of glucose-6-phosphate
hexokinases I, II, III
Found in the liver and pancreas
• Main function is to regulate blood glucose levels, especially after meals
• Low affinity for glucose (high Km)
• Hill coefficient = 1.5
• No product inhibition
• Glucose is high activity is turned on
• Normal glucose activity is reduced
hexokinase IV or glucokinase
what happend in step 2 of glycolosis (isomerization)
Isomerization of glucose-6-phosphate for fructose-6-phosphate, pyran ring to furan, enzyme Glucosephosphate isomerase
no atoms added or removed; molecular formula remains the same but chemical structure is changed
isomerization
what is step 3 of glycolosis (phosphorylation)
fructose-6-phosphate to fructose-1,6-bisphosphate with atp, enzyme Phosphofructokinase,
what is the rate limiting step in glycolosis
step 3
what happens in step 4 of glycolosis (cleavage)
fructose-1,6,-bisphosphate broken for glyceraldehyde-3-phosphate and dihyroxyacetone
phosphate, enzyme adolase
what happens in step 5 of glycolosis (isomerization)
dihyroxyacetone phosphate makes the 2nd glyceraldehyde-3-phosphate, enzyme triosephosphate, dhap to g3p
what is the energetics for the first 5 steps of glycolosis
2 kj/mol
which steps are irreversible for the priming phase
step 1 and 3
what is step 6 of glycolosis
Glyceraldehyde-3-phosphate is converted to 1,3- bisphosphoglycerate by electron transfer and addition of a phosphate group, enzyme Glyceraldehyde-3-phosphate dehydrogenase
what is the oxdizing agent in step 6 of glycolosis
NAD+
what happens in step 7 of glycolosis (transfer)
1,3-bisphosphoglycerate transfers a phosphate group to ADP forming ATP and 3-phosphoglycerate, enzyme Phosphoglycerate kinase
what happens in step 8 of glycolosis (isomerization)
Isomerization of 3-phosphoglycerate to 2- phosphoglycerate, enzyme Phosphoglycerolmutase
what happens in step 9 of glycolosis (dehydration)
Water is eliminated from 2-phosphoglycerate to form phosphenolpyruvate (PEP), better phosphoryl donor made, increased double bonds more unstable more phosphate release,
what happens in step 10 of glycolosis (transfer)
Phosphoenolpyruvate transfers a phosphate group to ADP forming ATP and pyruvate, enzyme Pyruvate kinase, inhibited by excess atp
glycolosis is ______ and releases _____ kj/mol
exergonic, 73.3 kj/mol
what are the three control points in glycolosis that undergo decreases in free energy and the enzymes are under allosteric control
step 1 hexokinsae inhibited by g6p, step 3 phosphofrcuctoskinase inhibited by ATP, step 10 pyruvate kinase inhibited by atp
NAD+ is requierd for ______ of glyolosis and is then recycled back into NADH
step 6
If O2 is available (aerobic), NADH is re-oxidized by the ___________ during oxidative
phosphorylation
electron transport chain
If O2 is unavailable (anaerobic), NADH is re-oxidized by the __________ to either lactate or ethanol
reduction of pyruvate
under anaerobic conditions what is the most important process for the regenration of NAD+ and what enzyme helps
pyruvate to lactate, Lactate dehydrogenase
skeletal muscle, supports anaerobic, favor pyruvate to lactate to regenerate NAD+
lactate dehydrogenase subunit
LDH5 (M4)
heart muscle, supports aerobic, More likely to convert lactate back to pyruvate to favor TCA cycle
lactate dehydrogenase subunit
LDH1 (H4)
lactate builds up in the muscle, leading to fatigue as it creates an acidic environment that inhibits
________________
muscle contraction
After exercise (O2 available),lactate is transported to liver and converted back to _______ and then ______
pyruvate, glucose
what are the steps of NADH being reoxidized to NAD+ for anaerobic alcohol fermentation (yeast)
decarboxylation of pyruvate, reduction of acetaldehyde accepts 2 electrons 1 proton and regenerates NAD+ to make ethanol
glucose units (a1-4) are attached by
linear glycosidic bonds
glucose units (a1-6) are attached by
branching glycosidic bonds
what is the role of glycogen
store glucose or supply glucose to glycolosis pathway
Glycogen synthesis or _______– process where glycogen is formed from glucose molecules
glycogenesis
________ is a highly branched polymer of glucose
glycogen
what are the 5 steps of glyogen synthesis (Ugly Iguanas Fight Enormous Bears)
glucose uptake phosphorylation, isomerization to glucose1phosphate, formation udp glucose, chain elongation, branching enzyme
what happens in step 1 of glycogen synthesis (uptake)
glucose transporters take glucose from blood and bring to cytosol, phosphorylated to glucose 6 phosphate
what enzymes are used in step 1 of glycogen synthesis
Glucokinase in liver, Hexokinase in muscle
Found in the liver, pancreas, and kidneys
glucose transporter
GLUT2
muscle and adipose tissue-Higher affinity for glucose
glucose transporter
GLUT4
what happens in step 2 of glycogen synthesis (isomerization)
Isomerization of glucose-6-phosphate to glucose-1-phosphate, enzyme Phosphoglucomutase
Glucose-1-phosphate + UTP=
UDP glucose +2Pi
why is udp glucose created in the 3rd step of glycogen synthesis
substrate and energy for enzyme glycogen synthase that will link glucose units
is the formation of UDP glycogen endergonic or exergonic
exergonic
What is UDP glycogen made up of
Uracil base + pentose sugar + 2 Phosphates
what happens in the first part of step 3 in glycogen synthesis
transfer UMP to g1P releases PPi, enzyme UDP-glucose pyrophosphorylase
what happens in the second part of step 3 in glycogen synthesis
PPi hysrolosis into PO4 3-, enzyme inorganic Pyrophosphatase
what happens in step 4 of glycogen synthesis (elongation)
Transfer of glucose from UDP- glucose to Tyr-194 of glycogenin, repeat until 8 glucose and glycogen synthase takes over, uses UDP glucose to add the glucose unit to non reducing end of existing glycogen chain makes a(1,4) glycosidic bond
primer protein initiates the first few glucose units called glycogen primer
glycogen synthesis elongation
Glycogenin
true or false: glycogen chain detaches from glycogenin protein in elongation
false
what does glycogen synthase require
growing glucose chain with free hydroxl at C4 on terminal glucose and UDP glucose
what is step 5 of glycogen synthesis
glycogen branching enzyme transfers 7 glucose units to site to produce a(1-6) glycosidic bond (branch point)
what are the rules for step 5 of glycogen synthesis
7 glucose residues is taken from chain of at least 11, branch point must be at least 4 residues away from other branch point
Glycogen breakdown or ________– process where glycogen is released back into glucose units and energy
glycogenolysis
what are the steps for glycogen breakdown (really interesting racoons)
release glucose1phosphate, isomerization g1p to g6p, remodeling glycogen
what is step 1 of glycogen breakdown
Glucose is cleaved from glycogen and reacts with Pi to make glucose-1- phosphate, enzyme glycogen phosphorylase
uses phosphate instead of water to cleave the glycosidic bond
phosphorolysis
what enzyme is used for the isomerization of g1p to g6p
phosphoglucomutase
why is aa remodeling step needed for glycogen breakdown
glycogen phosphorlyase cant break 1,6 branch points a debranching enzyme is needed
what 2 reactions are catalyzed in glycogen breakdown
transferase activity - shift block of three glucose connects from one branch to another, a16 glucosidase activity- hydrolsis of a16 glycosidic bond releases glucose
glycogen Phosphorylase ___ - phosphorylated, active, phosphorylation control
a
glycogen Phosphorylase ____ - dephosphorylated, less active, phosphorylation control
b
how does an organism control the glycogen synthesis and breakdown pathway
dual regulation-covalent modification (phosphorylation) allosteric control
glycogen ___ form - tense, less active, allosteric control conformation
t
glycogen ___-form - relaxed, more active, allosteric control conformation
r
why in phosphorylase A (phosphorylated), glucose favors the transition to the T-form (less active)
high glucose decreases need for cell to break down glycogen
explain what the t form does
exposes serine 14 (phosphorylation site) and permits dephosphorylation by phosphoprotein phosphatase
In phosphorylase B (dephosphorylated) ATP and/or Glucose-6-phosphate favor the T-form because…
ATP or G6P decreases need for cell to breakdown glycogen into glucose
in phosphorylase b why does amp favor the r form
high levels of amp indicate low energy status
what are the enzymes that can phosphorylate glycogen synthase
glycogen synthase kinase 3 (GSK3), protein kinase (PKA), and AMP-activated protein kinase (AMPK)
Glycogen synthase can be dephosphorylated by enzyme
protein phosphatase I
the body controls two opposite processes in opposite directions so they don't happen at the same time
reciprocal regulation
Pathway by which glucose is synthesized from pyruvate or other non-carbohydrate precursors during times of fasting, prolonged exercise, or low carbohydrate intake
gluconeogenesis
why is gluconeogenesis not a simple reversal of glycolosis
because of the three irreversible steps
what is the reverse of step 10 glycolosis
pyruvate+ATP→ oxaloacetate + GEP → PEP, Enzymes Pyruvate Carboxylase and PEP Carboxykinase, occurs in mitochondria| and mito cytoplasm, requires biotin atp acetyl coa activator, and |GTP
what is the reverse of step 3 glycolosis
F-1,6-BP → F-6-P enzyme Fructose- 1,6-Bisphosphatase
what is the reverse of step 1 glycolosis
G-6-P → Glucose enzyme Glucose-6-phosphatase
how does oxaloacetate get to the cytoplasm in the reversal of step 10 glycolosis
turns into malate and then converted back
Effectors (substrates, products, or coenzymes) of a pathway inhibit or activate an enzyme. (Responds rapidly to external stimuli.)
allosteric
Inhibition or activation of an enzyme depends on formation or breaking of a bond, frequently by phosphorylation or dephosphorylation. (Responds rapidly to external stimuli.)
covalent modification
Two opposing reactions, such as formation and breakdown of a given substance, are catalyzed by different enzymes, which can be activated or inhibited separately. (Responds rapidly to external stimuli.)
substrate cycles
as a regulator of metabolism high atp
inhibits glycolosis
the reversal of glycolosis is…
endergonic
gluconeogensis is…
exergonic
as a regulator of metabolism high amp
accelerates glycolysis, inhibits gluconeogenesis