Download Metabolism

Metabolism

Metabolism is all the chemical reactions that occur in an
organism

Nearly all the reactions in the living system are catalyzed by
enzymes

Metabolic pathways are a series of 2-20 enzyme catalyzed
steps that direct chemical reactions

Each of the participants in the chain of reactions is a
metabolite

Cellular respiration – food fuels are broken down within
cells and some of the energy is captured to produce ATP
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Catabolism

Conversion of large complex molecules into simpler,
smaller ones

Some of the reactions release chemical energy

A portion of this energy is captured as ATP (40%) and
the rest is released as heat

Cells break down excess carbohydrates first, then lipids

Cells conserve amino acids because anabolism require
more amino acids than lipids and only few
carbohydrates.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Anabolism

Conversion of small molecules to larger ones in the
process of biosynthesis

Require chemical energy

In general, biosynthesis is not a simple reversal of its
pathway for catabolism

Anabolism is used for:

Performance of structural maintenance and repair

Support of growth

Production of secretions

Building of nutrient reserves
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Oxidation, reduction and energy transfer
•
Oxidation is loss of electrons; Reduction is gain of
electrons
•
•
•
oxidation can also be the loss of H and reduction is the
gain of H
In oxidation/reduction reactions, one chemical is
oxidized, and its electrons are passed to another
(reduced, then) chemical.
The 2 reactions are always paired – when electrons pass
from a molecule to another, the electron donor is
oxidized and the electron recipient is reduced.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Oxidation, reduction and energy transfer
•
In a typical oxidation-reduction reaction, the reduced
molecule gains energy and Oxidized substances lose energy
•
Not all energy is gained by the reduced molecule because
some is released as heat and some is used to form ATP
http://www.emc.maricopa.edu/faculty/farabee/biobk/BioBookEnzym.html
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Cellular respiration: Coenzymes

When a substance is oxidized, the liberated hydrogen atoms do
not remain free but are transferred immediately by coenzyme to
another compound

Coenzymes act as hydrogen (or electron) acceptors

Many of the metabolic processes require the removal of
hydrogen - these reactions often involve a dehydrogenase
enzyme

Two coenzymes are commonly used to carry hydrogen atoms:


Nicotinamide adenine dinucleotide (NAD)
Flavin adenine dinucleotite (FAD) – a derivative of vitamin
B2
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
http://www.emc.maricopa.edu/faculty/farabee/biobk/BioBookEnzym.html
ATP shuttles chemical energy within the cell

In cellular respiration, some energy is stored in ATP molecules

ATP powers nearly all forms of cellular work

A typical cell has about a billion molecules of ATP, each last
for less than a minute before it is used

Rearrangement of atoms will either store or release energy
chemical reaction = rearrangement of atoms
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
This reaction supplies energy for cellular work:
Adenine
Phosphate
groups
Hydrolysis
Energy
Ribose
Adenosine triphosphate

Adenosine diphosphate
(ADP)
Two mechanisms to “capture” energy and make ATP


Substrate-level phosphorylation – phosphat groups are
transferred directly from a substrate
Oxidative phosphorylation – chemiosmotic process
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Mechanisms of ATP Synthesis: Substrate-Level
Phosphorylation

High-energy
phosphate groups are
transferred directly
from phosphorylated
substrates to ADP

ATP is synthesized via
substrate-level
phosphorylation in
glycolysis and the
Krebs cycle
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 24.4a
Mechanisms of ATP Synthesis:
Oxidative Phosphorylation

Uses the chemiosmotic
process whereby the
movement of substances
across a membrane is
coupled to chemical
reactions

Is carried out by the
electron transport
proteins in the cristae of
the mitochondria
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Cellular respiration
•
In cellular respiration, the chemical energy in various
nutrients, such as glucose, is transferred to ATP.
•
Cellular respiration can be divided into three metabolic
processes each occurs in a specific region of the cell.
•
Glycolysis occurs in the cytoplasm – breakdown of
glucose to pyruvic acid.
•
The Krebs cycle takes place in the matrix of the
mitochondria.
•
Oxidative phosphorylation via the electron transport
chain is carried out on the inner mitochondrial
membrane.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Carbohydrate Metabolism

Polysaccharides are
hydrolyzed into
monosaccharides

80% glucose

Hepatocytes convert
fructose and some of
galactose to glucose

Glucose is the preferred source
for ATP production

It is also used for the synthesis
of amino acids, glycogen and
triglycerides
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Aerobic respiration is the use of oxygen in cells.

Aerobic respiration can release energy from a molecule of
glucose to produce 36 ATP, shown in this equation.
C6H12O6+6O2 --Enzymes---> 6CO2+6H2O+36ATP

this formula gives energy for cell activities
Glucose
Oxygen
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Carbon
dioxide
Water
Energy
Glycolysis (anaerobic metabolism)

Glycolysis breaks a six-carbon glucose into two three-carbon
molecules - two molecules of pyruvic acid that moves to the
Krebs cycle

Glycolysis consume 2 ATP molecules but produces 4 ATP
molecules – net gain of 2 ATP

During the first half of the process ATP is “invested” to split
the glucose

The second half of the process the pyruvate is formed and
ATP is generated

During the process 2 molecules of NAD+ are reduced to form
2 NADH and 2H+ (NAD+ is the oxidized form – less energy
and NADH is the reduced form – more energy)
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
1st half – ATP “invested”
2nd half – ATP generated
2 Pyruvic acid
Glucose
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

The 2 ATP molecules that were generated during glycolysis
represent only 3% of the energy that is contained in the glucose
molecule

The pyruvic acid contain 90% of the energy that was originally
in the glucose molecule

The subsequent process of breaking down the pyruvate is
aimed to release this energy

The fate of pyruvic acid depends on the availability of oxygen:

In an anaerobic environment (no oxygen) it will be
converted into lactic acid. Lactic acid diffuses out of the
cells, arrives via bloodstream to the liver where it is
converted back into pyruvic acid

In aerobic environment, pyruvic acid will enter the Krebs
cycle
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
The tricarboxylic acid (TCA)/citric acid/Krebs cycle

The significance of the TCA cycle is that it takes the 3-carbon leftover from glycolysis (pyruvic acid) and breaks it down in such a
way as to yield a large amount of useable energy.

The pyruvic acid has three carbons. Before it enters the TCA
cycle, it is reduced to two carbons as acetate attached to
coenzyme-A (CoA). The combination is called acetyl-CoA.

During this process 1 molecule of CO2 and 2 of NADH are
released
CoA
2
Pyruvic
acid
Acetic
acid
1
CO2
3
Coenzyme A
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Acetyl-CoA
(acetyl-coenzyme A)
The tricarboxylic acid (TCA)/citric acid/Krebs cycle

Acetyl CoA (2 carbons) is attached to a 4-carbon oxaloacetic acid
molecule to form a 6-carbon citric acid.

The CoA is released intact and can bind another acetyl group

The citric acid is converted to a 4-carbon molecule releasing 2
molecules of CO2 and hydrogen atoms that are removed by NAD
(transform to NADH)

Than the 4-carbon molecule is being transformed and by that
releasing CO2 and H2O

The main goal of this process is to transfer
energy from the pyruvic acid to coenzymes
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Krebs Cycle


An eight-step cycle in which each acetic acid is
decarboxylated and oxidized, generating:

Three molecules of NADH + H+

One molecule of FADH2

Two molecules of CO2

One molecule of ATP
For each molecule of glucose entering glycolysis, two
molecules of acetyl CoA enter the Krebs cycle
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Input
Output
2
1 Acetic acid
2 CO2
ADP
3
Krebs
Cycle
3 NAD
4
FAD
5
6
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 6.11
Oxidative phosphorylation / Electron transfer system

Requires coenzymes and consumes oxygen

Key reactions take place in the electron transport system
(ETS)

The basic chemical reaction is:
2 H2 + O2  2 H2O
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Oxidative phosphorilation

Each carrier in the chain is reduced as it picks up electron
and than oxidized as it gives it up

The electron transfer release energy that is used to form ATP

Energy from the NADH is used to pump H+ from the matrix
of the mitochondria into the intermembrane space (proton
pump)

That results in high H+ concentration in the intermembrane
space

These are moved through special channels and the movement
results in energy release that is used to form ATP
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Electronic Energy Gradient

The transfer of energy from NADH + H+ and FADH2 to
oxygen releases large amounts of energy

This energy is released in a stepwise manner through the
electron transport chain

The electrochemical proton gradient across the inner
membrane:


Creates a pH gradient

Generates a voltage gradient
These gradients cause H+ to flow back into the matrix via
ATP synthase
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Summary of ATP Production
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 24.11
Glycogenesis and Glycogenolysis


Glycogenesis – formation
of glycogen when glucose
supplies exceed cellular
need for ATP synthesis
Glycogenolysis –
breakdown of glycogen in
response to low blood
glucose
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 24.12
Lipid Metabolism - classes of lipids in the human body

Triglycerides

main storage form of metabolic fuel (9 kcal/g).

Can supply weeks or months of starvation (stored
carbohydrates can supply about a day)

This molecule is composed of three molecules of
fatty acid (which may all be the same or all different)
attached to a glycerol molecule.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
phospholipids

Phospholipids have only two
molecules of fatty acid attached to
glycerol with the third hydroxyl
group on glycerol bonded to a
phosphate and then to a polar
alcohol group.

This gives the molecule the
structure with a polar "head" (the
phosphate and alcohol) and a long
non-polar
"tail",
the
latter
contributed by the fatty acid
molecules.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Steroids

Steroids DO NOT contain fatty acids.

They contain a mostly hydrocarbon structure, but
instead of being linear like fatty acids, they are
composed of ring structures.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Fatty acids

Fatty acids consist of a long
hydrocarbon chain with a
terminal carboxyl group.

The hydrocarbon chain
commonly contains 15-20
carbons.

This type of structure is highly
non-polar and hence water
insoluble.
stearic acid palmitic acid oleic acid
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Lipid catabolism - lipolysis


Lipids broken down into pieces that can be converted
into pyruvate

Triglycerides are split into glycerol and 3 fatty acids

Glycerol enters TCA cycle after being broken to
pyruvic acid in the cytosol.
Fatty acids enter the mitochondrion
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Fatty acid activation
•
Fatty acids must be activated before they can be carried
into the mitochondria, where fatty acid oxidation occurs.
•
Once activated, the fatty acyl CoA is transported into the
mitochondrial matrix.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Lipid catabolism - lipolysis

Long chain fatty acyl CoA is degraded by Beta-oxidation.

The products of beta-oxidation are:



acetyl CoA

FADH2, NADH and H+
Fate of acetyl CoA

Oxidation by the Krebs cycle to CO2 and H2O.

In liver only, acetyl CoA may be used for ketone body
synthesis.
Fate of the FADH2 and NADH + H+

FADH2 and NADH + H+ are oxidized by the mitochondrial
electron transport system, yielding ATP.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Lipids and energy production

Lipids are stored as droplets in the cytoplasm which
make them more difficult to access than carbohydrate
reserves

Lipids are processed in the mitochondria and the
mitochondrial activity is limited by the availability of
oxygen

As a result, lipids cannot provide large amounts in
ATP in a short amount of time
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Lipid synthesis (lipogenesis)

Almost any organic molecule can be used to form
glycerol

Essential fatty acids cannot be synthesized and must be
included in diet


Linoleic and linolenic acid come from plants

They are used for prostaglandins and some
phospholipids production
Lipogenesis occur in the liver and adipose tissue
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
ketogenesis

Ketogenesis occurs in the mitochondrial matrix in the liver

When carbohydrate intake is inadequate the body starts to break down
lipids.

Ketone bodies are produced when:

fasting or starvation conditions

or after a meal rich in triglycerides

not enough insulin in the blood

Breaking lipids will result in excess acetyl CoA

The ability of acetyl CoA to enter the Krebs cycle is limited

The result is accumulation of acetyl CoA

The acetyl CoA is then used in ketogenesis (synthesis of keton
bodies/ketones)

Ketone bodies are produced in small quantities in healthy persons.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Low CHO intake,
insufficient insulin
Fatty acids flood the liver
Acetyl-CoA
Many Acetyl-CoA
Limited
Acetyl-CoA
Ketone
Citric Acid
Bodies
Cycle
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Lipid transport and distribution

Lipids are hydrophobic molecules that need to be transported
carried by proteins

Lipoproteins are lipid-protein complexes.

Each type has a different function, but all are transport “vehicles”

The superficial coating of phodpholipids and proteins make the
complexes soluble



Proteins in the outer shell are called apoproteins
The inner core is built out of lipids
Lipoprotein are categorized by their density which results from
the ratios between lipids (low density) and proteins (high
density)
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Lipoproteins types

General categories of lipoproteins, listed in order from larger and less
dense (more fat than protein) to smaller and more dense (more
protein, less fat):

Chylomicrons

carry ingested triglycerides (fat) from the intestine to the liver and to
adipose tissue for storage.

Enter lacteals and carried by lymph into systemic circulation.

Lipoprotein lipase - enzyme that breaks down complex lipids because
the chylomicrons are too big to diffuse across capillary walls

Found in capillary walls of liver, adipose tissue, skeletal and cardiac
muscle

Releases fatty acids and monoglycerides that diffuse to interstitial
fluids
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
•Retrieved from "http://en.wikipedia.org/wiki/Lipoprotein"
Lipid Transport and Utilization
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 25.11a
Lipoproteins types - Very Low Density lipoproteins
(VLDL)

form by the hepatocytes

carry newly synthesized triglycerides from the liver to adipose tissue
for storage

After depositing some of their triglycerides they are converted to
LDLs
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Lipoproteins types - Low Density Lipoproteins (LDL)

carry 75% of cholesterol from the liver to cells of the body.

LDL enters the cells where it is being broken down to
release cholesterol

when a cell has sufficient cholesterol it will prevent by
negative feedback the entrance of LDL into it

When present in excessive amount, LDL deposit
cholesterol in and around smooth muscle fibers in the
arteries (that is why sometimes it is referred to as the "bad
cholesterol" lipoprotein).
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Lipoproteins types - High Density Lipoproteins (HDL)

collects cholesterol from the body's tissues and
brings it back to the liver.

Sometimes referred to as the "good cholesterol"
lipoprotein
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Protein metabolism

Body can synthesize 100,000-140,000 different proteins

Each protein contain a combination of the same 20
amino acids

Cellular proteins are continuously recycled in the
cytoplasm
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Protein Metabolism

Excess dietary protein results in amino acids being:

Oxidized for energy

Converted into fat for storage

Amino acids must be deaminated prior to oxidation for
energy

Deaminated amino acids are converted into:


Pyruvic acid

One of the keto acid intermediates of the Krebs cycle
These events occur as transamination,
deamination, and keto acid modification
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
oxidative
Oxidation of Amino Acids

Transamination – switching of an amine group from an amino
acid to a keto acid (usually -ketoglutaric acid of the Krebs
cycle)



Typically, glutamic acid is formed in this process
Oxidative deamination – the amine group of glutamic acid is:

Released as ammonia

Combined with carbon dioxide in the liver

Excreted as urea by the kidneys
Keto acid modification – keto acids from transamination are
altered to produce metabolites that can enter the Krebs cycle
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Synthesis of Proteins


Amino acids are the most important anabolic nutrients,
and they form:

All protein structures

The bulk of the body’s functional molecules
A complete set of amino acids is necessary for protein
synthesis

All essential amino acids must be provided in the
diet
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings