Title: Camp 1
1Metabolism
2Key words
- Metabolism definition
- Catabolism and anabolism definition, example
- Identify/distinguish structure of coenzymes
- Identify structure of ATP
3What is Metabolism?
The study of the biochemical reactions in an
organism, including the coordination, regulation
and energy needs
- Definition Metabolism is the sum total of the
chemical reactions of biomolecules in an organism - Metabolism consists of
- catabolism the breakdown of larger molecules
into smaller ones an oxidative process that
releases energy - anabolism the synthesis of larger molecules from
smaller ones a reductive process that requires
energy
- Catabolism the oxidative breakdown of nutrients
- Anabolism the reductive synthesis of
biomolecules
4Terminology in Metabolism
- Metabolic pathway A sequence of reactions, where
the product of one reaction becomes the substrate
for the next reaction. - - either linear pathway or cyclic pathway
- - metabolic pathways proceed in many stages,
allowing for efficient use of energy - Metabolites intermediates in metabolic pathway
light
Eg. 6 CO2(g) 6 H2O(l) ? C6H12O6(aq) 6
O2(g) Anabolism
photosynthesis
C6H12O6 (aq) 6O2 (g) ? 6CO2 (g)
6H2O Catabolism
respiration
5 Metabolic pathway
6Metabolic pathway linear or cyclic
7A Comparison of Catabolism and Anabolism
- Metabolism is the sum total of the chemical
reactions of biomolecules in an organism
8Metabolism
- Metabolism involves the energy flow in the cell
- Photoautotroph via photosynthesis transfers the
energy to heterotrophs - Heterotrophs obtain the energy through
oxidation/reduction of organic compounds
(carbohydrate, lipid and proteins) - ? Food supplies the energy
- Energy ATP
9The Role of Oxidation and Reduction in Metabolism
- Oxidation-Reduction (redox) reactions are those
in which electrons are transferred from a donor
to an acceptor - oxidation the loss of electrons the substance
that loses the electrons is called a reducing
agent - reduction the gain of electrons the substance
that gains the electrons is called an oxidizing
agent - Carbon in most reduced form- alkane
- Carbon in most oxidized form- CO2 (final product
of catabolism)
Reduced
Oxidized
10Oxidation and Reduction in Metabolism
Reduction gain e
Oxidation less e
Oxidizing agent e acceptor
reducing agent e donor
11Metabolism Features
A group of noncovalently associated enzymes that
catalyze 2 or more sequential steps in
metabolic/biochemical pathway
- Metabolic pathway
- Enzymes multienzymes
- Coenzymes
- ATP produced or used
- Regulation of metabolic pathway
- Feedback inhibition or
- Feed-forward activation
12Metabolism Regulation
- Regulation of metabolic pathway
- Feedback inhibition product (usually ultimate
product) of a pathway controls the rate of
synthesis through inhibition of an early step
(usually the first step) - A ? B ? C ? D ? E ? P
- Feed-forward activation metabolite produced
early in pathway activates enzyme that catalyzes
a reaction further down the pathway - A ? B ? C ? D ? E ? P
E1
E2
E3
E4
E5
E1
E2
E3
E4
E5
13Coenzymes
- Coenzymes in metabolism
- NAD/NADH
- NADP/NADPH
- FAD/FADH2
- Coenzyme A (CoASH) activation of metabolites
Electron carriers
14NAD/NADH An Important Coenzyme
- Nicotinamide adenine dinucleotide (NAD) is an
important coenzyme - Acts as a biological oxidizing agent
- The structure of NAD/NADH is comprised of a
nicotinamide portion. - It is a derivative of nicotinic acid
- NAD is a two-electron oxidizing agent, and is
reduced to NADH
Reduced form, NADH carries 2 electrons
15NADP/NADPH Also comprised of nicotinamide
portion
- Nicotinamide adenine dinucleotide phosphate
(NADP) oxidizing agent - NADPH involves in reductive biosynthesis
- Differ with NAD at ribose (C2 contain a
phosphoryl group, PO32- - As electron carrier in photosythesis and pentose
phosphate pathway
Reduced form, NADPH carries 2 electrons
Anabolism
16The Structures Flavin Adenine Dinucleotide (FAD)
- FAD is also a biological oxidizing agent
- FAD can accept one-electron or two-electron
The terminal e acceptor (O2) can accept only
unpaired e (e must be transferred to O2 one at a
time)
FADH carries 1 electron, FADH2 carries 2 electrons
17FAD/FADH2
- FADH (semiquinone form) carries 1 electron,
- FADH2 (fully reduced hydroquinone form) carries 2
electrons
1
1
Formation of fully reduced hydroquinone form
bypass the semiquinone form
18Coenzyme A in Activation of Metabolic Pathways
- A step frequently encountered in metabolism is
activation - activation the formation of a more reactive
substance - A metabolite is bonded to some other molecule and
the free-energy change for breaking the new bond
is negative. - Causes next reaction to be exergonic
19Coenzyme A (CoASH)
- Coenzyme A functions as a carrier of acetyl and
other acyl groups - Has sulfhydryl/thiol group
Thioester bond
CoASH
Acetyl-CoA is a high-energy compound because
of the presence of thioester bond hydrolysis
will release energy
20ATP- high energy compound
- ATP is essential high energy bond-containing
compound - Phosphorylation of ADP to ATP requires energy
-
- Hydrolysis of ATP to ADP releases energy
nucleotide
Phosphorylation the addition of phosphoryl
(PO32-) group/Pi (inorganic phosphate)
21Metabolism (2)
22ATP- high energy compound
- ATP is essential high energy bond-containing
compound - Phosphorylation of ADP to ATP requires energy
-
- Hydrolysis of ATP to ADP releases energy
nucleotide
Phosphorylation the addition of phosphoryl
(PO32-) group/Pi (inorganic phosphate)
23The Phosphoric Anhydride Bonds in ATP are High
Energy Bonds
- High Energy bonds-
- bonds that require or release convenient amounts
of energy, depending on the direction of the
reaction - Couple reactions the energy released by one
reaction, such as ATP hydrolysis, provides energy
for another reactions to completion in
metabolic pathway
Phosphoanhydride /
24Couple reaction example
25Role of ATP as Energy Currency
Phosphorylation of ADP requires energy from
breakdown of nutrients (catabolism)
The energy from hydrolysis of ATP will be used in
the formation of products (anabolism)
26Metabolism of Carbohydrate
Catabolism Anabolism
27Major pathways of carbohydrate metabolism.
Fig 8.1 3rd ed
28Key words
- Glycolysis, the fate for pyruvate
- Substrate-level phosphorylation and oxidative
phosphorylation
29Glycolysis
- Glycolysis is the first stage of glucose
metabolism - Glycolysis converts 1 molecule of glucose to 2
units of pyruvate (three C units) and the process
involves the synthesis of ATP and reduction of
NAD (to NADH) - The pathway has 10 steps/reactions
- Glycolysis are divided into 2 stages/phases,
- Phase 11st 5 reactions
- Phase 22nd 5 reactions
Linear pathway
30Glycolysis
- Glycolysis are divided into 2 stages/phases,
- Phase 11st 5 reactions
- Energy investment
- A hexose sugar (glucose) is split into
- 2 molecules of three-C metabolite
(glyceraldehyde-3-phosphate GAP). The process
consume 2 ATP - Phase 22nd 5 reactions
- Energy recovery
- The two molecules of GAP are converted to 2
molecules of pyruvate with the generation of 4
ATP and 2 NADH. - Overall equation
- Glucose 2 NAD 2 ADP 2Pi ?
- 2 pyruvate 2 NADH 2 ATP 2 H2O 4H
Glycolysis has a net profit of 2 ATP per
glucose
31The Reactions of Glycolysis
glucokinase
1
- Phosphorylation of glucose to give
glucose-6-phosphate - Isomerization of glucose-6-phosphate to give
fructose-6-phosphate - Phosphorylation of fructose-6-phosphate to yield
fructose-1,6-bisphosphate - Cleavage of fructose-1,6,-bisphosphate to give
glyceraldehyde-3-phosphate and dihydroxyacetone
phosphate - Isomerization of dihydroxyacetone phosphate to
give glyceraldehyde-3-phosphate isomerase enzyme
Use ATP
2
Use ATP
3
phosphofructokinase
4
5
32The Reactions of Glycolysis (Contd)
- Oxidation of glyceraldehyde-3-phosphate to give
1,3-bisphosphoglycerate - Transfer of a phosphate group from
1,3-bisphosphoglycerate to ADP to give
3-phosphoglycerate - Isomerization of 3-phosphoglycerate to give
2-phosphoglycerate - Dehydration of 2-phosphoglycerate to give
phosphoenolpyruvate - Transfer of a phosphate group from
phosphoenolpyruvate to ADP to give pyruvate
Glyceraldehyde-3-P dehydrogenase
oxidation
6
Electron acceptor NAD
transfer
7
Phosphorylation of ADP to ATP
isomerization
8
dehydration
9
transfer
10
Phosphorylation of ADP to ATP
33Glycolysis
- Dephosphorylation of ATP
- Phosphorylation of ADP
- Oxidation of intermediates and reduction of NAD
to NADH by dehydrogenase reactions - - step 6
- - glyceraldehyde-3-phosphate dehydrogenase
-
By kinase enzyme at step 1, 3, 7 and 10
34ATP production
- ATP is produced by phosphorylation of ADP - is
through substrate-level phosphorylation - Substrate-level phosphorylation the process of
forming ATP by phosphoryl group transfer from
reactive intermediates to ADP - 1,3-bisphosphoglycerate and phosphoenolpyruvate
high-energy intermediates/compounds - Oxidative phosphorylation the process of
forming ATP via the pH gradient as a result of
the electron transport chain.
Glycolysis - Step 7 and 10
35Fates of Pyruvate From Glycolysis
- Once pyruvate is formed, it has one of several
fates - In aerobic metabolism- pyruvate will enter the
citric acid cycle, end product in aerobic
metabolism CO2 and H2O - In anaerobic metabolism- the pyruvate loses CO2
- produce ethanol alcoholic fermentation
- produce lactate anaerobic glycolysis
36Anaerobic Metabolism of Pyruvate
- Under anaerobic conditions, the most important
pathway for the regeneration of NAD is reduction
of pyruvate to lactate - Lactate dehydrogenase (LDH) is a tetrameric
isoenzyme consisting of H and M subunits H4
predominates in heart muscle, and M4 in skeletal
muscle
In muscle, during vigorous exercise demand of
ATP ? but O2 is in short supply ? is largely
synthesized via anaerobic glycolysis which
rapidly generates ATP rather than through slower
oxidative phosphorylation
37Alcoholic Fermentation
In anaerobic bacteria
- Two reactions lead to the production of ethanol
- Decarboxylation of pyruvate to acetaldehyde
- Reduction of acetaldehyde to ethanol
- Pyruvate decarboxylase is the enzyme that
catalyzes the first reaction - This enzyme require Mg2 and the cofactor,
thiamine pyrophosphate (TPP) - Alcohol dehydrogenase catalyzes the conversion
of acetaldehyde to ethanol
38NAD Needs to be Recycled to Prevent Decrease in
Oxidation Reactions
39Structure of cell
Cytoplasm/ Cytosol
40 41Where does the Glycolysis Take Place?
Cytosol
Glycolysis is universal!
42Citric Acid Cycle Krebs Cycle, Tricarboxylic
acid Cycle (TCA)
43Metabolism Features
A group of noncovalently associated enzymes that
catalyze 2 or more sequential steps in
metabolic/biochemical pathway
- Metabolic pathway
- Enzymes multienzymes
- Coenzymes
- ATP produced or used
44Couple reaction example
45Coenzymes
- Coenzymes in metabolism
- NAD/NADH
- NADP/NADPH
- FAD/FADH2
- Coenzyme A (CoASH) activation of metabolites
Electron carriers
46Glycolysis
- Glycolysis are divided into 2 stages/phases,
- Phase 11st 5 reactions
- Energy investment
- A hexose sugar (glucose) is split into
- 2 molecules of three-C metabolite
(glyceraldehyde-3-phosphate GAP). The process
consume 2 ATP - Phase 22nd 5 reactions
- Energy recovery
- The two molecules of GAP are converted to 2
molecules of pyruvate with the generation of 4
ATP and 2 NADH. - Overall equation
- Glucose 2 NAD 2 ADP 2Pi ?
- 2 pyruvate 2 NADH 2 ATP 2 H2O 4H
Glycolysis has a net profit of 2 ATP per
glucose
47Fates of Pyruvate From Glycolysis
- Once pyruvate is formed, it has one of several
fates - In aerobic metabolism- pyruvate will enter the
citric acid cycle, end product in aerobic
metabolism CO2 and H2O - In anaerobic metabolism- the pyruvate loses CO2
- produce ethanol alcoholic fermentation
- produce lactate anaerobic glycolysis
Glycolysis in cytoplasm
48Key words
- Definition citric acid cycle
- Explain the citric acid cycle
- Distinguish between glycolysis and citric acid
cycle - Understand ?-oxidation catabolism of lipid
-
49Citric acid cycle
- Requires aerobic condition
- Amphibolic (both catabolic anabolic)
- Serves 2 purposes
- Oxidize Acetyl-CoA to CO2 to produce energy (ATP
reducing power of NADH FADH2)-involved in the
aerobic catabolism of carbohydrates, lipids and
amino acids - Supply precursors for biosynthesis of
carbohydrates, lipids, amino acids, nucleotides
and porphyrins
50Citric Acid Cycle Krebs Cycle Tricarboxylic
acid Cycle (TCA)
51 TCA
- Circular pathway
- Two-carbon unit needed at the start of the citric
acid cycle - The two-carbon unit is acetyl-CoA
- Involves 8 reactions
- The overall reaction from 1 acetyl-CoA produce 3
NADH, 1 FADH2, 2 CO2 and 1 GTP (equivalent to 1
ATP)
52Pyruvate is converted to Acetyl-CoA activation
of pyruvate
- Pyruvate dehydrogenase complex is responsible for
the conversion of pyruvate to acetyl-CoA - Five enzymes in complex
- Requires the presence of cofactors TPP (thymine
pyrophosphate), FAD, NAD, and lipoic acid and
coenzyme A (CoA-SH) - The overall reaction of the pyruvate
dehydrogenase complex is the conversion of
pyruvate, NAD, and CoA-SH to acetyl-CoA, NADH
H, and CO2
Oxidation of pyruvate and reduction of NAD
3C
Pyruvate pyruvic acid
2C
Thioester, high energy compound
53Coenzyme A (CoASH)
- Coenzyme A functions as a carrier of acetyl and
other acyl groups - Has sulfhydryl/thiol group
Thioester bond
CoASH
Acetyl-CoA is a high-energy compound because
of the presence of thioester bond hydrolysis
will release energy
54Features of TCA
Mitochondrial matrix
Electron acceptor NAD and FAD
- Circular pathway
- Two-carbon unit needed at the start of the citric
acid cycle - The two-carbon unit is acetyl-CoA
- Involves 8 reactions
- The overall reaction from 1 acetyl-CoA produce 3
NADH, 1 FADH2, 2 CO2 and 1 GTP (equivalent to 1
ATP)
X 2
How about 1 molecule of glucose?
55Citric acid cycle - features
- Oxidation decarboxylation
- - CO2 leaves at step 3 and 4
- Oxidation of intermediates and reduction of NAD
to NADH by dehydrogenase reactions - - step 3, 4 and 8
- - isocitrate dehydrogenase
- - a-ketoglutarate dehydrogenase
- - malate dehydrogenase
- Oxidation of intermediates and reduction of FAD
to FADH2 by succinate dehydrogenase reaction - - step 6
- Phosphorylation of GDP to GTP step 5
56Where does the Citric Acid Cycle Take Place?
- In eukaryotes, cycle takes place in the
mitochondrial matrix
In prokaryotes?
Cytoplasm
57The Central Relationship of the Citric Acid Cycle
to Catabolism
- TCA involves 8 series of reactions that oxidizes
the acetyl group of acetyl-CoA to 2 molecules of
CO2 and the energy is conserves in NADH, FADH2
and high-energy compound, GTP - Acetyl-CoA synthesize from pyruvate
(glycolysis product)
Guanosine Tri-Phosphate
58Aerobic catabolism
- NADH, FADH2 from glycolysis and TCA will enter
the Electron Transport Chain (ETC) to produce
more ATP (oxidative phosphorylation) - 1 NADH 2.5 ATP,
- 1 FADH2 1.5 ATP
- ETC take place in mitochondria - inner
membrane (eukaryotes)
In ETC
In prokaryotes?
Plasma membrane
59Oxidation of Pyruvate Forms CO2 and ATP
Aerobic metabolism is more efficient than
anaerobic metabolism
60Citric acid cycle - amphibolic
- Amphibolic (both catabolic anabolic)
- Serves 2 purposes
- Oxidize Acetyl-CoA to CO2 to produce energy (ATP
reducing power of NADH FADH2)-involved in the
aerobic catabolism of carbohydrates, lipids and
amino acids - Supply precursors for biosynthesis (anabolism) of
carbohydrates, lipids, amino acids, nucleotides
and porphyrins
Replenish TCA- catabolism of amino a. and fatty
a. Anabolic pathway
Require aerobic condition
61Differences between glycolysis TCA cycle
- Glycolysis is a linear pathway TCA cycle is
cyclic - Glycolysis occurs in the cytosol and TCA is in
the mitochondrial matrix - Glycolysis does / does not require oxygen TCA
requires oxygen (aerobic)
62Lipids are Involved in Generation and Storage of
Energy
- The oxidation of fatty acids (FA)in
triacylglycerols are the principal storage form
of energy for most organisms - Their carbon chains are in a highly reduced form
- The energy yield per gram of fatty acid oxidized
is greater than that per gram of carbohydrate
oxidized
63Catabolism of Lipids - triacylglycerol
- Lipases catalyze hydrolysis of bonds between
fatty acid and the rest of triacylglycerols - Phospholipases catalyze hydrolysis of bonds
between fatty acid and the rest of
phosphoacylglycerols - May have multiple sites of action
64Catabolism of fatty acid - ?-Oxidation
- ?-Oxidation a series of reactions that cleaves
carbon atoms two at a time from the carboxyl end
of a fatty acid - The complete cycle of one ?-oxidation requires
four enzymes/steps - Take place in mitochondria matrix
Spiral pathway
1 round of ?-oxidation yield 1 NADH, 1 FADH2
and 1 acetyl-CoA
65REVISION
66- Catabolism the oxidative breakdown of nutrients
- Anabolism the reductive synthesis of biomolecules
- Catabolism features
- Release energy (ADP? ATP)
- Oxidizing agent (NAD, FAD)
- Anabolism features
- Use energy (ATP ? ADP)
- Reducing agent (NADH ,FADH2)
Metabolism the sum total of biochemical
reaction carried out by organism
67Metabolism
- Metabolism involves the energy flow in the cell
- Photoautotroph via photosynthesis transfers the
energy to heterotrophs - Heterotrophs obtain the energy through
oxidation/reduction of organic compounds
(carbohydrate, lipid and proteins) - ? Food supplies the energy
- Energy ATP
68Major pathways of carbohydrate metabolism.
Fig 8.1 3rd ed
69Glycolysis
Linear pathway
- Glycolysis is the first stage of glucose
metabolism - Glycolysis converts 1 molecule of glucose to 2
units of pyruvate (three C units) and the process
involves the synthesis of ATP and reduction of
NAD (to NADH) - The pathway has 10 steps/reactions
- Glycolysis are divided into 2 stages/phases,
- Phase 11st 5 reactions
- Phase 22nd 5 reactions
70Fates of Pyruvate From Glycolysis
- Once pyruvate is formed, it has one of several
fates - In aerobic metabolism- pyruvate will enter the
citric acid cycle, end product in aerobic
metabolism CO2 and H2O - In anaerobic metabolism- the pyruvate loses CO2
- produce ethanol alcoholic fermentation
- produce lactate anaerobic glycolysis
Glycolysis in cytoplasm
71ATP- high energy compound
ATP energy carrier / an energy transfer agent
- ATP is essential high energy bond-containing
compound - Phosphorylation of ADP to ATP requires energy
-
- Hydrolysis of ATP to ADP releases energy
nucleotide
Phosphorylation the addition of phosphoryl
(PO32-) group/Pi (inorganic phosphate)
72Coenzyme A (CoASH)
- Coenzyme A functions as a carrier of acetyl and
other acyl groups - Has sulfhydryl/thiol group
Thioester bond
CoASH
Acetyl-CoA is a high-energy compound because
of the presence of thioester bond hydrolysis
will release energy
73 TCA
- Circular pathway
- Two-carbon unit needed at the start of the citric
acid cycle - The two-carbon unit is acetyl-CoA
- Involves 8 reactions
- The overall reaction from 1 acetyl-CoA produce 3
NADH, 1 FADH2, 2 CO2 and 1 GTP (equivalent to 1
ATP)
74Citric acid cycle - amphibolic
- Amphibolic (both catabolic anabolic)
- Serves 2 purposes
- Oxidize Acetyl-CoA to CO2 to produce energy (ATP
reducing power of NADH FADH2)-involved in the
aerobic catabolism of carbohydrates, lipids and
amino acids - Supply precursors for biosynthesis (anabolism) of
carbohydrates, lipids, amino acids, nucleotides
and porphyrins
Replenish TCA- catabolism of amino a. and fatty
a. Anabolic pathway
Require aerobic condition
75Where does the Citric Acid Cycle Take Place?
- In eukaryotes, cycle takes place in the
mitochondrial matrix
In prokaryotes?
Cytoplasm