Download Introduction to metabolism. Specific and general pathways of

Introduction to metabolism. Specific and
general pathways of carbohydrates, lipids
and proteins metabolism.
• 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 carboncontaining compounds.
Heterotrophs are divided into aerobs and anaerobs.
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)
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:
(a) Linear
(b) Cyclic
(c) Spiral pathway
(fatty acid
biosynthesis)
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.
Anabolism and catabolism are coupled by energy
Metabolism Proceeds by Discrete Steps
• Multiple-step pathways
permit control of energy
input and output
Single-step vs multi-step
pathways
• Catabolic multi-step
pathways provide energy
in smaller stepwise
amounts
• Each enzyme in a multistep 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
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
Levels of Metabolism Regulation
1. Nervous system.
2. Endocrine system.
3. Interaction between organs.
4. Cell (membrane) level.
5. Molecular level
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
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
Regulatory role of a protein kinase,
amplification by a signaling cascade
The initial signal may be amplified by the “cascade” nature of this signaling
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.
Glycerol
Catabolism
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.
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)
Compartmentation of metabolic processes
The chemistry of metabolism
There are about 3000 reactions in human cell.
All these reactions are divided into six categories:
1. Oxidation-reduction reactions
2. Group transfer reactions
3. Hydrolysis reactions
4. Nonhydrolytic cleavage reactions
5. Isomerization and rearrangement reactions
6. Bond formation reactions using energy from ATP
Experimental Methods
for Studying Metabolism
• Add labeled substrate to tissues, cells, and
follow emergence of intermediates. Use
sensitive isotopic tracers (3H, 14C etc)
• Verify pathway steps in vitro by using
isolated enzymes and substrates
• Study of the mutations in genes associated
with the production of defective enzymes
• Use metabolic inhibitors to identify
individual steps and sequence of enzymes in
a pathway