Bioenergetic processes: biological oxidation.

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• Bioenergetic processes biological oxidation.

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• Metabolism - the entire network of chemical
  reactions carried out by living cells. Metabolism
  also includes coordination, regulation and energy
  requirement.
• Metabolites - small molecule intermediates in the
  degradation and synthesis of polymers

Most organism use the same general pathway for
extraction and utilization of energy. All living
organisms are divided into two major
classes Autotrophs can use atmospheric carbon
dioxide as a sole source of carbon for the
synthesis of macromolecules. Autotrophs use the
sun energy for biosynthetic purposes.
Heterotrophs obtain energy by
ingesting complex carbon-containing
compounds. Heterotrophs are divided into aerobs
and anaerobs.
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Common features of organisms
1. Organisms or cells maintain specific internal
concentrations of inorganic ions, metabolites and
enzymes 2. Organisms extract energy from external
sources to drive energy-consuming reactions 3.
Organisms grow and reproduce according to
instructions encoded in the genetic material 4.
Organisms respond to environmental influences 5.
Cells are not static, and cell components are
continually synthesized and degraded (i.e.
undergo turnover)
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A sequence of reactions that has a specific
purpose (for instance degradation of glucose,
synthesis of fatty acids) is called metabolic
pathway.
Metabolic pathway may be
(c) Spiral pathway (fatty acid biosynthesis)
(a) Linear (b) Cyclic
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Metabolic pathways can be grouped into two paths
catabolism and anabolism
Catabolic reactions - degrade molecules to create
smaller molecules and energy Anabolic reactions
- synthesize molecules for cell maintenance,
growth and reproduction
Catabolism is characterized by oxidation
reactions and by release of free energy which is
transformed to ATP. Anabolism is
characterized by reduction reactions and by
utilization of energy accumulated in ATP
molecules.
Catabolism and anabolism are tightly linked
together by their coordinated energy
requirements catabolic processes release the
energy from food and collect it in the ATP
anabolic processes use the free energy stored in
ATP to perform work.
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Anabolism and catabolism are coupled by energy
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Metabolism Proceeds by Discrete Steps
Single-step vs multi-step pathways

• Multiple-step pathways permit control of energy
  input and output
• Catabolic multi-step pathways provide energy in
  smaller stepwise amounts
• Each enzyme in a multi-step pathway usually
  catalyzes only one single step in the pathway
• Control points occur in multistep pathways

A multistep enzyme pathway releases energy in
smaller amounts that can be used by the cell
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Metabolic Pathways Are Regulated

• Metabolism is highly regulated to permit
  organisms to respond to changing conditions
• Most pathways are irreversible
• Flux - flow of material through a metabolic
  pathway which depends upon (1) Supply of
  substrates (2) Removal of products (3) Pathway
  enzyme activities

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• Levels of Metabolism Regulation
• Nervous system.
• Endocrine system.
• Interaction between organs.
• Cell (membrane) level.
• Molecular level

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Feedback inhibition

• Product of a pathway controls the rate of its own
  synthesis by inhibiting an early step (usually
  the first committed step (unique to the
  pathway)

Feed-forward activation

• Metabolite early in the pathway activates an
  enzyme further down the pathway

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Covalent modification for enzyme regulation

• Interconvertible enzyme activity can be rapidly
  and reversibly altered by covalent modification
• Protein kinases phosphorylate enzymes ( ATP)
• Protein phosphatases remove phosphoryl groups

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Regulatory role of a protein kinase,
amplification by a signaling cascade
The initial signal may be amplified by the
cascade nature of this signaling
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Stages of metabolism
Catabolism
Stage I. Breakdown of macromolecules (proteins,
carbohydrates and lipids to respective building
blocks. Stage II. Amino acids, fatty acids and
glucose are oxidized to common metabolite (acetyl
CoA) Stage III. Acetyl CoA is oxidized in citric
acid cycle to CO2 and water. As result reduced
cofactor, NADH2 and FADH2, are formed which give
up their electrons. Electrons are transported via
the tissue respiration chain and released energy
is coupled directly to ATP synthesis.
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Glycerol
Catabolism
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Catabolism is characterized by convergence of
three major routs toward a final common
pathway. Different proteins, fats and
carbohydrates enter the same pathway
tricarboxylic acid cycle.
Anabolism can also be divided into stages,
however the anabolic pathways are characterized
by divergence. Monosaccharide synthesis begin
with CO2, oxaloacetate, pyruvate or lactate.

Amino
acids are synthesized from acetyl CoA, pyruvate
or keto acids of Krebs cycle.

Fatty acids are constructed
from acetyl CoA. On the next stage
monosaccharides, amino acids and fatty acids are
used for the synthesis of polysaccharides,
proteins and fats.
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Compartmentation of Metabolic Processes in Cell

• Compartmentation of metabolic processes permits
• - separate pools of metabolites within a cell
• - simultaneous operation of opposing metabolic
  paths
• - high local concentrations of metabolites
• Example fatty acid synthesis enzymes (cytosol),
  fatty acid breakdown enzymes (mitochondria)

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Compartmentation of metabolic processes
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The chemistry of metabolism

• There are about 3000 reactions in human cell.
• 
  
  All these reactions
  are divided into six categories
• Oxidation-reduction reactions
• Group transfer reactions
• Hydrolysis reactions
• Nonhydrolytic cleavage reactions
• Isomerization and rearrangement reactions
• Bond formation reactions using energy from ATP

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1. Oxidation-reduction reactions
Oxidation-reduction reactions are those in which
electrons are transferred from one molecule or
atom to another
Enzymes oxidoreductases

• oxidases
  - peroxidases
  - dehydrogenases
  -oxigenases

Coenzymes NAD, NADP, FAD, FMN
Example
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2. Group transfer reactions
Transfer of a chemical functional group from one
molecule to another (intermolecular) or group
transfer within a single molecule (intramolecular)
Enzymes transferases
Examples
Phosphorylation
Acylation
Glycosylation
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3. Hydrolysis reactions

• Water is used to split the single molecule into
  two molecules

Enzymes hydrolases
- esterases -
peptidases
- glycosidases
Example
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4. Nonhydrolytic cleavage reactions

• Split or lysis of a substrate, generating a
  double bond in a nonhydrolytic (without water),
  nonoxidative elimination

Enzymes lyases
Example
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5. Isomerization and rearrangement reactions
Two kinds of chemical transformation 1.
Intramolecular hydrogen atom shifts changing the
location of a double bond.

2. Intramolecular rearrangment of
functional groups.
Enzymes isomerases
Example
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6. Bond formation reactions using energy from ATP

• Ligation, or joining of two substrates
• Require chemical energy (e.g. ATP)

Enzymes ligases (synthetases)