Module 7 Flashcards
Metabolic pathways
difference between anabolic and catabolic processes
Anabolism converts simple sugars, amino acid, fatty acids, nitrogenous base to complex structures like polysaccharides,proteins, lipid and nucleic acid using ATP, NADH, NADPH and FADH2
Catabolism uses carbohydrates, fats, protein and convert to energy depleted end products like CO2, H2O, NH3 while producing energy like ATP etc
structures of the key energy transfer molecules of ATP
Phosphate group, main base is adenosine (2 cyclic nitrogenous base)
energy transfer molecules of CoA
acetly group, pantothenic acid(2 double O, 1 OH), beta-mercaptoethylamine(sulphide end) transfer molecule, Vitamine B5, adenosine base, phosphate connected to sugar
energy transfer molecules of FADH2/FAD
a pair of sugar with one adenosine and transfer molecule nicotinamide(cyclic with O double bond with NH2)
energy transfer molecules of NADH/NAD+
FMN, 3 cyclic at the end, nitrogen gains H
What is reaction 1 of glycolysis
Phosphorylation of Glucose
Glucose to glucose 6 phosphate, irreversible(ΔG is small), Mg 2+ needed
enzyme used : hexokinase in most tissue and glucokinase in liver
Reaction 2 of glycolysis
Isomerisation of Glucose-6Phosphate to Fructose-6-Phosphate(ring of 6 to 5), reversible, higher ΔG, Mg 2+ needed
Enzyme used: PHOSPHOHEXOSE ISOMERASE
Reaction 3 of glycolysis
Conversion of Fructose-6Phosphate to Fructose-1,6-bisphosphate, irreversible, ΔG small, first commited step(rate-limiting step) Mg 2+ needed
Enzyme used : PFK-1
Reaction 4 of glycolysis
Cleavage of F-1,6-bP
reversible( called aldol condensation), get 2 product, DHAP(dihydroxyacetone phosphat) and GA-3-P( glyceraldehyde 3-phosphate)
Enzyme used: aldolase
Reaction 5 of glycolysis
Isomerisation of DHAP to Glyceraldehyde-3-Phosphate
adding H to the =O, reversible. A special glutamate amino acid in the active site (Glu165) performs the transfer
Enzyme used: Triose Phosphate Isomerase
How many steps are there in the Payoff Phase
5
Reaction 6 of glycolysis
Oxidation of Glyceraldehyde-3-Phosphate to 1,3-Bisphosphoglycerate,
, generate NADH. Adding a phosphate, Rapid turnover of NAD+ is only achieved under anaerobic conditions
Enzyme used: Glyceraldehyde 3-Phosphate Dehydrogenase (3gpd)
Reaction 7 of glycolysis
Conversion of 1,3-Bisphosphoglycerate to 3-phosphoglycerate
Formation of ATP, transferring phospate. First ATP generated. irreversible. Mg2+ needed
Enzyme used: Phosphoglycerate Kinase
Reaction 8 of glycolysis
Mutase Reaction Converting 3-phosphoglycerate to 2-phosphoglycerate.
Moving the C3 phosphate to C2. Mg2+ needed
Enzyme used: Phosphoglycerate Mutase
Reaction 9 of glycolysis
Dehydration of 2phosphoglycerate to Phosphoenolpyruvate
remove the hydroxyl and hydrogen group to form PEP. For H2O.
Enzyme used: Enolase
Reaction 10 of glycolysis
Production of ATP from the Conversion of PEP to Pyruvate
Attaching the phosphate to ADP, irreversible
The enzyme used: Pyruvate Kinase
What does chemotherapeutic agent inhibit
hexokinase (eg. 2-deoxyglucose)
What is Warburg Hypothesis
most cancer cells produce energy by anaerobic glycolysis rather than by oxidation of pyruvate in the mitochondria
What are the enzyme used for glycolysis in chronological order
(1) HexoK
(2) PHI
(3) PFK1
(4) Aldolase
(5) TPI
(6) GAPDH
(7) PGK
(8) PGM
(9) Enolase
(10) PK
What are the 3 irreversible step of gluconeogenesis(GNG)
(1) Conversion of Pyruvate to PEP occurs via Oxaloacetate using mitochondrialPyruvate Carboxylase& cytosolicPEP carboxykinase
(2) Conversion of F-1,6-bisP to F-6P is catalyzed by Fructose 1,6bisphosphatase
(3) Conversion of G-6-P to Glucose occurs in the ER lumenusing Glucose-6-Phosphatase
step 1A of reversible step gluconeogenesis(GNG)
Pyruvate Carboxylase
Uses ATP to attach carboxylic acid to pyruvate using biotin as a cofactor. Change from pyruvate to oxaloacetate. Mitochondrial enzyme
Structure of pyruvate
CH3-C=-O,C=-O,O
Structure of glycerate
C3H5O4. carboxylic end, C2,3 with hydroxyl
step 1B reversible step of gluconeogenesis(GNG)
Adding phosphate to 2C oxaloacetate using GTP, lose the CO2. From oxaloacetate to phosphoenolpyruvate(PEP)
Enzyme used Phosphoenol pyruvate Carboxykinase(PEPCK)
step 2 reversible step of gluconeogenesis(GNG)
Fructose-1,6-bisphosphate is converted to Fructose-6-phosphate by Fructose-1,6-Bisphosphatase. Occurs in the cytosol
step 3 reversible step of gluconeogenesis(GNG)
Conversion of Glucose-6-Phosphate to Glucose by Glucose-6 Phosphatase
occurs in the lumen of the Endoplasmic Reticulum in hepatocytes of the Liver and in the cortex of the Kidney.
structure of substrates and products for the Cori cycle
Lactate>blood lactate>Lactate>glucose>blood glucose>glycogen>lactate
ATP produced when glycogen converts to lactate, used when converting Lactate to glucose
why is lactate dehydrogenase important during anaerobic glycolysis
Generating NAD+ in step 6
Describe the metabolic fate of lactate produced in the muscle and how this is linked to metabolism in the liver.
Lactate will be convert to blood lactate and transferred to Liver to using ATP to synthesis glucose during recovery
What can pyruvate turn into?
alanine, ethanol, lactate, oxaloacetate and acetyl CoA(last 2 are form inside the mitochondrial matrix)
chemical equation of fermentation
Pyruvate >(pyruvate decarboxylase) acetaldehyde > (alcohol dehydrogenase) ethanol
Anaerobic Glycolysis chemical equation
Pyruvate . L-Lactate using lactate dehydrogenase
LDH plays an important role in regenerating NAD+
High amounts of Lactic acid can produce acidosis.
Structure of L-Lactate
CH3—H, OH, C=-OO
What is the structure of glycogen
Glycogen is a polysaccharide comprised of α-D-glucose units linked via α1→4 glycosidic bonds withα1→6 branch points
What is the structure of starch
1,4 glycosidic bond, all R group are on the same side
What is the structure of cellulose
1,4 glycosidic bond, all R group are on the alternating side
What is glycogen
storage form of carbohydrate in the body
Why is glycogen important
critical during fasting, since liver glycogen provides a source of blood glucose
What is Muscle glycogen for
cannot give rise to blood glucose, but is used to power muscle contraction for extended periods of time
What is glycogenolysis for
breakdown of glycogen & involves the enzymes (1) Glycogen Phosphorylase, (2) Debranching enzyme and (3) Phosphoglucomutase
What is glycogenesis
synthesis of glycogen & involves the enzymes (1) UDP-glucose pyrophosphorylase, (2) Glycogen Synthase, (3) amylo (1 → 4) to (1 → 6) transglycosylase(glycogen-branching enzyme)
Which side the glycogenolysis cleave
The nonreducing end(left side)
What is the debranching enzyme for
oligo ( α 1 > 6) to ( α 1 > 4) glucan-transferase] transfers from the branch to the nearby nonreducing end , hydrolyzes the α1>6 linkage to release free glucose
What is the use of phosphoglucamutase
transfers a phosphoryl group on Glucose-1-Phosphate from C-1 to C-6 to form Glucose-6-Phosphate, which is freely reversible.
What is the final product of glycogenolysis
glucose 6-phosphate, to convert to glucose or 2 pyruvate for 2 ATP
UDP-Glucose Pyrophosphorylase
synthesizes UDP-glucose from UTP and Glucose-1-Phosphate and also produces pyrophosphate (PPi)
Glycogen Synthase
Elongation of glycogen
Glycogen Branching Enzyme
[Amylo (1>4) to (1>6) Transglycosylase]
catalyzes the transfer of a block of 6 or7 glucose residues from the nonreducing end of a glycogen branch having at least 11 residues to the C6 hydroxyl group of a glucose residue
Glycogenin
intitiate of a new glycogen chain. Glycogenin is both the primer on which new chains are synthesized and the enzyme that catalyzes their assembly.
PDH Complex
considered the 1stcontrol point of the Krebs cycle
E1 (pyruvate dehudrogenase), E2 (dihydrolipoyl transacetylase), E3 (Dihydrolipoyl dehydrogenase)
Low G, irreversible, converts from pyruvate to acetyl-CoA. producing NADH
Why are B group vitamins important?
Most are vital for energy storage, conversion
Steps of the citric cycle
1) condensation
2a) dehydration
2b) hydration
3) oxidative decarboxylation
4) oxidative decarboxylation
5) substrate-level phosphorylation
6) dehydrogenation
7) hydration
8) dehydration
What is the the reaction 1 of kreb cycle
formation of citrate from oxaloacetate and acetyl-CoA catalyzed by Citrate Synthase. highly exergonic because it involves the hydrolysis of a thio-ester(i.e.S-CoA) irreversible( low ΔG
What is the the reaction 2 of kreb cycle
Citrate is converted to isocitrate in two-steps (via a cis-aconitate intermediate) catalyzed by Aconitase
What is the the reaction 3 of kreb cycle
Isocitrate is then converted to α-ketoglutarate by Isocitrate dehydrogenase producing CO2 and also redox energy in the form of NADH that is equivalent to 2.5 ATP. 2nd control point
What is the the reaction 4 of kreb cycle
α-ketoglutarate is converted to succinyl-CoA by the
α -ketoglutarate
dehydrogenase complex and represents the 3rd & last control point in the cycle.
What does The sequence structure and functional similarities between PDH and α-KDH complexes suggest
divergent evolution
What is the the reaction 5 of kreb cycle
Succinyl-CoA is then converted to succinate by succinyl Co-A synthetase, which involves energy release in the form of hydrolysis of a thioester bond that is used to drive the synthesis of GTP. high GTP inhibits oxidative metabolism
What is the the reaction 6 of kreb cycle
succinate is converted to fumarate by Succinate Dehydrogenase which utilizes FAD as a cofactor and thus produces a FADH2
how many ATP does FAH2 equal to
1.5
What is the the reaction 7 of kreb cycle
Fumarateisconvertedto L-malate via a carbanion intermediate by the enzyme Fumarase (also known as Fumarate Hydratase)
Fumarase
The enzyme is highly stereospecific and thus cannot bind or react with cis isomer of fumarate (i.e. maleate) orthe D-malate isomer
What is the the reaction 7 of kreb cycle
conversion of malate to oxaloacetate by Malate Dehydrogenase produces another NADH
how many ATP does NADH equal to
2.5
Total number of ATP form in Aerobic Glycolysis, PDH Complex & Krebs Cycle
30-32
What is the sequence of product produced in the kreb cycle
acetyl-CoA > citrate > isocitrate > α-ketoglutarate > succinyl-CoA > succinate > fumarate > malate > oxaloacetate
What does Oxidative phosphorylation mean
process of transforming redox energy formed under aerobic conditions during Glycolysis and the Citric Acid Cycle (i.e. NADH and FADH2) into chemical energy in the form of ATP
How many major steps of Oxidative Phosphorylation
4
What is the step 1 of Oxidative Phosphorylation
Transfer of electrons from NADH to Complex I and/or from FADH2 to Complex II
What is the step 2 of Oxidative Phosphorylation
Flow of electrons through large multi-component inner mitochondrial membrane complexes and mobile electron transporters of the Electron Transport Chain
What is the step 3 of Oxidative Phosphorylation
Pumping of protons (H+) from the matrix to the intermembrane space (IMS) using the proton pumps of Complex I, III and IV as electrons flow through these complexes
What is the step 4 of Oxidative Phosphorylation
Flow of protons (H+) from the IMS through the F0 component of ATP Synthase (F0F1 ATPase) back into the matrix resulting in the rotation of the F0 component & γ subunit of F1 and the synthesis of ATP from ADP and Pi by the F1 component.
Describe how the Electron Transport Chain is linked to the Krebs Cycle.
It uses NADH made in kreb to drive ATP synthesis as it pumps H+ into the intermembrance space
Where does the electron transport chain occur
pumping of protons from the matrix into the intermembrane space (IMS)creates a proton gradient that is used to drive ATP synthesis
Function of complex I
Uses H from NADH, pump 4H+ to the intermembrance space. attaching 2H to coenzyme Q
What is coenzyme Q
lipophillic inner mitochondrial membrane dwelling mobile electron carrier that transfers electrons from Complex I and Complex II to Complex III.
What is the oxidised form of Q
ubiquinone
What is the reduced form of Q known as
the reduced form (QH2) is referred to as ubiquinol
What is enzyme II called
succinate dehydrogenase, not a H+ pump
What does complex III compromised of
Cytochrome c and cytochrome b
What is the cytochrome c protein for
soluble protein that resides in the inter membrane space that accepts electrons from Complex III and donates them to Complex IV
What does cytochrome c contain
prosthetic group Heme C with a central Fe3+ atom that becomes reduced to Fe2+ after accepting an e- from Complex III, and returns to Fe3+ when the e- is donated to Complex IV
What does complex IV do
Pumps 2H+ use ½ O2 per 2e i.e. per NADH or FADH2 and converts to H2O
How is ATP synthase synthesise ATP
Mitochondrial ATP Synthase uses the H+ gradient formed via the pumping of protons by Complexes I, III & IV to drive the unfavourable synthesis of ATP from ADP + Pi
What does ATP synthase compromised of
FO (stalk) & a F1 (head) component
What does the inner mitochondrial membrane compromised of
α, β, γ, δ, ε subunits
What mechanic is used to drive the ATP synthesis
rotational catalysis mechanism
What are the components of F1 in ATP synthase
3 nonequivalent adenine nucleotide-binding sites, one for each α/βpair.
What is β-ATP conformation in ATP synthase for
binds ATP tightly, a second is in the β-ADP conformation, which binds ADP + Pi. third is in the β-empty conformation
What causes the rotation of the γ subunit
proton motive force as H+ is pumped through the Fo component
What is phosphate transocase for
to pump phosphate hydrogen into the mitochondria. a symporter
How many Protons is required for ATP for yeast
10 protons are required to turn the ATPsynthase through one complete cycle to synthesize 3 ATP and 3 H to pump 3 Pi in.
How many Protons is required for ATP for mammals
8 protons are required to turn the ATP synthase through one complete cycle. 3 H to pump 3 Pi in.
How many protons are pumped into IMS per NADH
10, 2.5 ATP
How many protons are needed to make 1 ATP
approx 4
How many protons are pumped into IMS per FADH2
6, 1.5 ATP
How many H+ are pump in complex I
4
How many H+ are pump in complex III
4
How many H+ are pump in complex IV
2
What is adenine nucleotide translocase for
transport ATP out and ADP in, antiporter
Where does FADH2 oxidised
complex II
