Metabolism - Websupport1

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Lecture 2
Insert figure 6.1 here
PowerPoint® Lecture Slides are prepared by Dr. Isaac Barjis, Biology Instructor
MCAT Prep. Exam
Enzymes
1
Metabolism

Cells break down organic molecules to
generate energy (ATP)
 Energy is used for: growth, cell division,
contraction, secretion, and other functions
 Metabolism is all the chemical reactions that
occur in an organism
 Chemical reactions provide energy and
maintain homeostasis:



metabolic turnover
growth and cell division
special processes, such as secretion, contraction, and
action potential propagation
Metabolism
Metabolic reactions could be either catabolic
(catabolism) or anabolic (anabolism)
 Anabolism

Anabolism is the formation of new chemical
bonds to produce new organic molecules
 New Organic molecules are needed for/to:

Performance of structural maintenance and repairs
 Support of growth
 Production of secretions
 Building of nutrient reserves

Metabolism

Catabolism
Catabolism is the metabolic reactions that
breaks down organic substrates in order to
release energy
 Catabolic reactions occur in series of steps
 Catabolic reactions generate energy by breaking
down large molecules to small molecule


Small molecules enter Mitochondria to release more
energy
Cells and Mitochondria




Cells provide small organic molecules for their
mitochondria
Mitochondria produce ATP that is used by the
cell to perform cellular functions i.e. cells feed
mitochondria nutrient and in return mitochondria
provide the cells with energy (ATP).
Mitochondria accept only specific organic
molecules e.g. Pyruvic Acid, acetyl coenzyme A
Large organic nutrients (e.g. Glucose) are
broken down into smaller fragments (e.g.
Pyruvic Acid) in the cytoplasm, before they
could enter mitochondria
Cells and Mitochondria

Mitochondria breaks down the molecules to
carbon dioxide, water, and generates more
energy (ATP) via two pathways:
1. TCA cycle
 2. Electron transport system (ETS)

Carbohydrate Metabolism

Glycolysis is the process of breakdown of
glucose into pyruvic acid
 Glycolysis occur in the cytoplasm and it
requires:


One molecule of glucose + 2 ATP + 4ADP + 2NAD +
inorganic phosphate + cytoplasmic enzymes
Glycolysis generates:


Two pryruvic acid + 4ATP +2ADP + 2NADH
The net gain of ATP of glycolysis is 2ATP (it produces 4ATP
but two of the ATP are used)
Carbohydrate Metabolism

Aerobic metabolism (cellular respiration)


•
•
Pyruvic acid will enter mitochondria and generate more ATP via
TCA cycle and ETS
Two pyruvates = 34 ATP
The chemical formula for this process is
C6H12O6 + 6 O2  6 CO2 + 6 H2O
Anaerobic metabolism (fermentation)
•
•
•
In the absence of oxygen pyruvic acid will not enter mitochondria
Pyruvic acid will go through the process of anaerobic respiration and
will be converted into Lactic acid
This process dose not generate any ATP
Glycolysis: Steps in Glycolysis
1)
2)
3)
4)
Glucose (a 6 carbon molecule)
enters the cell
As soon as glucose is inside the
cell, a phosphate is added to
carbon number 6, and the new
molecule is called glucose 6
phosphate. This reaction is called
phosphorylation and it requires
one ATP, enzyme called
hexokinase.
Glucose 6 phosphate goes
through the second
phosphorylation reaction and a
phosphate is added to carbone
number 1. The new molecule
produced as a result is called
Fructose 1,6 Bisphosphate
The Fructose 1,6 bisphosphate (6
carbon molecule with phosphates
attached to carbon 1 and carbon
6) will split into two 3 carbon
molecule:
1)
2)
5)
Glyceraldehyde 3
phosphate
Dihydroxyacetone
Each 3 carbon molecule will
become a pyruvic acid through
number of steps (see the diagram
on the left)
Mitochondrial ATP Production
(cellular respiration)

The two pyruvic acid molecules will enter
mitochondria
In the mitochondria pyruvic acid will join
Coenzyme A (CoA) to form acetyl CoA before
entering the TCA cycle.
 TCA cycle will break down pyruvic acid
completely



Decarboxylation
Hydrogen atoms passed to coenzymes

Oxidative phosphorylation
The TCA Cycle Steps
1)
2)
3)
4)
5)
6)
7)
8)
9)
Pyruvic acid combine with coenzyme
A to form acetyl coenzyme A. This
reaction releases NADH and carbon
dioxide
Acetyl is a 2 carbon molecule. Acetylcoenzyme A will give the two carbon
molecule (acetyl) to the 4 carbon
molecule (oxaloacetic acid)
The 4 carbon molecule will become a 6
carbon molecule (citric acid)
Citric acid will go through number of
steps and will become back a 4 carbon
molecule .
The TCA cycle will begin with
formation of citric acid and end with
formation of oxaloacetic acid.
The TCA cycle will run twice for one
molecule of glucose, because one
molecule of glucose produces two
pyruvic acid and each pyruvic acid
turns once cycle
Each cycle of TCA will generate 3NADH,
1FADH2, and 1GTP
NADH and FADH2 will enter the electron
transport system and generate ATP
One NADH = 3ATP and one FADH2 = 2ATP
(see ETS)
The TCA Cycle
•
Pyruvic acid (a 3 carbon molecule) requires NAD and Coenzyme to form Acetyl coenzyme A
•
This reaction will generate NADH, carbon dioxide and acetyl coenzyme A. Notice that pyruvic
acid is a 3 carbon molecule , in this reaction one of the carbons was released as carbon
dioxide is formed and two carbon is left as a acetyl
•
Acetyl coenzyme A will transfer the acetyl to oxaloacetic (a 4 carbon molecule)
acid and coenzyme A will becomee free. 4 carbon molecule from oxaloacetic acid
and two carbon from acetyl will generate a 6 carbon molecule (citric acid)
•
•
The free coenzyme A will be reused by another pyruvic acid.
Citric acid will go through number of steps (e.g. it will become isocetric acid then
ketoglutaric acid and so on)and eventually will become oxaloacetic acid
The TCA Cycle
•
Citric acid will go through number of steps (e.g. it will become isocetric acid then
ketoglutaric acid and so on)and eventually will become oxaloacetic acid
Oxidative phosphorylation and the
ETS
Requires coenzymes and consumes oxygen
 Key reactions take place in the electron
transport system (ETS)



Cytochromes of the ETS pass electrons to
oxygen, forming water
The basic chemical reaction is:
2 H2 + O2  2 H2O
Electron Transport System (ETS)
ETS is sequence of proteins called
cytochromes
 Each cytochrome has:

A protein - embedded in the inner membrane of
a mitochondrion,
 A pigment

Electron Transport System (ETS)





STEP1: coenzyme strips a pair of hydrogen atoms from a
substrate molecule.
STEP2: NADH and FADH2 deliver hydrogen atoms to
coenzymes embedded in the inner membrane of a
mitochondrion.
STEP3: Coenzyme Q accepts hydrogen atoms from FMNH2
and FADH2 and passes electrons to cytochrome b.
STEP4: Electrons are passed along the electron transport
system, losing energy in a series of small steps. The
sequence is cytochrome b to c to a to a3.
STEP5: At the end of the ETS, an oxygen atom accepts the
electrons, creating an oxygen ion (O–). This ion has a very
strong affinity for hydrogen ions (H+); water is produced.
Oxidative Phosphorylation
Energy yield of glycolysis and cellular
respiration

Per molecule of glucose entering these
pathways
Glycolysis – has a net yield of 2 ATP
 Electron transport system – yields approximately
28 molecules of ATP
 TCA cycle – yields 2 molecules of ATP

The Energy Yield of Aerobic
Metabolism
The Energy Yield of Aerobic
Metabolism
The Energy Yield of Aerobic
Metabolism
The Energy Yield of Aerobic
Metabolism
The Energy Yield of Aerobic
Metabolism
The Energy Yield of Aerobic
Metabolism
The Energy Yield of Aerobic
Metabolism
A Summary of the Energy Yield of
Aerobic Metabolism
Synthesis of glucose and glycogen

Gluconeogenesis

Synthesis of glucose from noncarbohydrate
precursors such as lactic acid, glycerol, amino acids


Liver cells synthesis glucose when carbohydrates are
depleted
Glycogenesis

Formation of glycogen


Glucose stored in liver and skeletal muscle as glycogen
Important energy reserve
Key Concepts
Process
Location
Molecules produced
ATP
NADH
FADH
CO2
Glycolysis
cytoplasm
4
2
0
0
Fermentation/anaerobic
respiration
cytoplasm
0
0
0
0
Transition/Intermediate
steps (Pyruvate to Acetyl
CoA)
Mitochondria
0
1
0
1
TCA
Mitochondria
1
3
1
2
ETS
Mitochondria (inner
Mitochondrial
Membrane
NADH
= 3ATP
FADH2
= 2ATP
0
0
0
28
Carbohydrate Breakdown and Synthesis
Lipid catabolism

Lipolysis
Lipids broken down into pieces that can be
converted into pyruvate
 For example triglycerides are split into glycerol
and fatty acids

Glycerol enters glycolytic pathways
 Fatty acids enter the mitochondrion

Lipid catabolism

Beta-oxidation


Breakdown of fatty acid molecules into
2-carbon fragments
Lipids and energy production

Used when glucose reserves are limited
Beta Oxidation
•
•
•
•
In beta oxidation long chain of fatty acids are broken down into fragments of two
carbons.
Say we have a fatty acid chain that is 18 carbon long. During beta oxidation
fragments of two carbon will be removed from the chain of fatty acid. So after the
first round of reaction (as shown in the figure) a fatty acid chain that is 16 carbon
long will remain, after the second round of reactions a fatty acid chain that 14
carbon long will remain
For each round of reaction two carbon will be removed from the chain. As two
carbons are removed from the chain, NADH, FADH2 and Acetyl CoA will be
generated.
The steps in beta oxidation:
1)
2)
Coenzyme A bind to fatty acid. This step requires one ATP
This reaction will prepare fatty acid for beta oxidation and generate a fatty
acid attached to CoA
Beta Oxidation
3)
The first round of beta oxidation will generate one NADH, one FADH2
and one Acetyl CoA
4) Acetyl CoA will enter TCA cycle and generate 3NADH, 1FADH and 1GTP.
3NADH = 9ATP, 1FADH2 = 2ATP, and GTP = 1ATP.
Beta Oxidation
5)
NADH and FADH2 will enter the ETS and generate ATP
1NADH = 3ATP
1FADH2 = 2ATP
Summary :
one round of beta oxidation will generate :
NADH = 3ATP
FADH2 = 2ATP
Acetyl CoA = 12ATP
So if each round of beta oxidation produces 17ATP, then one molecule of
fat will produce a lot more ATP (energy) than one molecule of glucose.
Remember that glucose produced 2ATP in glycolysis and 34/36ATP via
TCA and ETS
Protein Metabolism
Amino acid catabolism




If other sources inadequate, mitochondria can break down
amino acids
 TCA cycle
The first step in amino acid catabolism is the removal of the
amino group (-NH2)
The amino group is removed by transamination or
deamination
 Transamination – attaches removed amino group to a
keto acid
 Deamination – removes amino group generating NH4+
Proteins are an impractical source of ATP production
Oxidation, Reduction, and Energy
Transfe








Enzymatic steps of oxidative phosphorylation involve oxidation and
reduction
The loss of electrons is oxidation; the acceptance of electrons is
reduction
Electron donor is oxidized (loss energy) and electron recipient
reduced (gain energy)
Reduced molecule does not acquire all the energy released by
oxidized molecule – thus some energy is released as heat, and
formation of ATP
Coenzyme acts as intermediary that accepts electrons from one
molecule and transfer it to another
In Kreb Cycle NAD and FAD remove hydrogen atoms from organic
substrates
NADH and FADH2, the reduced forms of NAD and FAD, transfer their
hydrogen to other coenzymes
Protons are released, and the electrons, which carry the chemical
energy, enter a sequence of oxidation–reduction reactions
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