Download Cellular Metabolism

Cellular Metabolism
The Main Function of Metabolism
 Metabolism = living cells use nutrients in many chemical
reactions that provide energy for vital processes and
activity.
 Homeostasis = a healthy and relatively constant internal
environment.
 To maintain homeostasis, the body regulates its systems to
avoid dangerous lacks or excesses.
 Ex. You breathe to take in oxygen and expel carbon dioxide
 Normal metabolism helps make homeostasis possible
(allow body to maintain or regain an “even keel”
The Metabolic Process
 Chemical balance – just like a car who needs
hydrogen and carbon to run our body needs the
right balance of nutrients and other substances
in our body
 Oxygen – (like “burning of gasoline that make a
engine run) many metabolic processes require
oxygen to take place (breathing)
 Temperature – (a car wont start it it’s temp. is too
low) an organism’s body temperature must be
within a certain range
 Removal of waste products – (exhaust system to
rid water vapor and carbon monoxide) the waste
products of metabolism are water and carbon
dioxide, these are carried in the blood to the
Energy for Metabolism
 During metabolism, energy is both used and
produced
 Energy originates from the sun, plants trap
energy, humans eat plant they gain nutrients
which provide energy for metabolism
 Of the 6 essential nutrients, protein,
carbohydrates and fats supply energy for
metabolism
 Glycogen = the form of carbohydrates stored in the
muscles
 Remaining carbohydrates are converted to fat
 Protein is use for body mass, excess amounts are
converted to fat
Catabolism & Anabolism
 Metabolism is 2 separate process
 Catabolism = breaking down complex molecules into
simpler ones during chemical reactions
 Nutrients are broken down into simple material which can enter the
cell, which then releases energy
 Anabolism = the combining of molecules during
chemical processes in order to build the materials of
living tissue
 Molecules broken down by catabolism are reconstructed into body
cells ex. Protein in peanut butter becomes protein in your muscles
through anabolic reactions
 Cytoplasm = colloidal substance consisting of
organic and inorganic substances, including
proteins and water found in a living cell. This is
the main component of both animal and plant
cells.
 Catabolism breaks down food to make cytoplasm which the
body uses for maintenance during anabolic process
Catabolism and Anabolism
Catabolic Reaction (glycogen breaks down, which releases energy)
Glycogen
Glucose
Anabolic Reaction (glycogen is created, which takes energy)
Glucose
Glucose
Glycogen
The ATP Cycle
 Adenosine Triphosphate = Certain molecules serve as
energy warehouse
 ATP molecules combine the compound adenosine with 3
phosphate groups, forming a chain A-P-P-P
 Energy is carried in the bonds between phosphate groups
 When a cell needs energy the bond between the two
phosphate groups is broken and the third group transfers
to another molecule.
 With only 2 phosphate groups remaining ATP becomes
ADP which will latter turn back to ATP trough using
energy to link with another phosphate group reforming
ATP
Storing Energy – Energy is stored when a third phosphate group
bonds to ADP, forming ATP
ENERGY
P
A
P
P
A
P
P
P
Using Energy – When a cell needs energy, a phosphate bond in ATP
breaks, release energy and produces ADP and separate phosphate group
ENERGY
A
P
P
P
A
P
P
P
Chemical Balance during
Metabolism
 The cells in the body are mostly cytoplasm
walled in by:
 Membranes = thin layers of tissue (these are
semipermeable)
 Semipermeable = they allow varying amounts of
specific substances to pass through them
 The open door policy can lead to a chemical imbalance
 Osmosis = the movement of fluid through a semipermeable cell
membrane to create an equal concentration of solution on both
sides
 Metabolic rate = how fast the chemical
processes for metabolism takes place
Body Temperature
 We have mechanisms to keep our body temperature
fairly stable
 Ex. In a cold room, you shiver to increase body heat
 In cold-blooded creatures, (lizards) – body temperature is
more dependent on environmental temperature.
 Lizard metabolic rate rises as it lies in the sun – thus the
metabolic rate varies more in a given day than a healthy
human’s rate
Body Size
 Small animals like a rabbit have more surface area so
they lose body heat more quickly, thus their metabolic
rate is much higher.
 In one minute a mouse breathes 150 times, elephant 6 times
and a human 16 times.
 In 2005 61% of the US population is considered overweight (I
am sure it’s higher now)
Questions
1. How is metabolism related to homeostasis?
2. Describe an environment in which
metabolism can occur.
3. How do humans get energy?
4. How are carbohydrates metabolized?
5. How are anabolism and catabolism related?
6. How is energy transferred from nutrients to
the body’s cells?
Questions Continued
7. How does a body maintain its supply of ATP?
8. Why is osmosis necessary for metabolism?
9. Why is your metabolic rate different from an
alligator’s?
10. How does your metabolic rate compare to
small animals?
11. Do you use energy while sleeping? – Explain.
12. How will your body respond if you start
skipping meals?
13. How can you prevent lactic acid buildup?
Why do these techniques work?
Cellular Metabolism
 Cellular metabolism refers to all of the
chemical processes that occur inside living
cells.
Energy
 Energy can exist in two states:
 Kinetic energy – energy of motion.
 Potential energy – stored energy.
 Chemical energy – potential energy stored in
bonds, released when bonds are broken.
 Energy can be transformed form one state to
another.
Energy
 The ultimate source
of energy for most
living things is the
sun.
Free Energy
 Free energy – the energy available for doing
work.
 Most chemical reactions release free energy – they
are exergonic.
 Downhill
 Some reactions require the input of free energy –
they are endergonic.
 Uphill
Enzymes
 Bonds must be destabilized before any reaction
can occur – even exergonic.
 Activation energy must be supplied so that the
bond will break.
 Heat – increases rate at which molecules collide.
 Catalysts can lower activation energy.
Enzymes
 Catalysts are chemical substances that speed
up a reaction without affecting the products.
 Catalysts are not used up or changed in any
way during the reaction.
 Enzymes are important catalysts in living
organisms.
Enzymes
 Enzymes reduce the
amount of activation
energy required for a
reaction to proceed.
 Enzymes are not
used up or altered.
 Products are not
altered.
 Energy released is
the same.
Enzymes
 Enzymes may be pure proteins or proteins
plus cofactors such as metallic ions or
coenzymes, organic group that contain groups
derived from vitamins.
Importance of ATP
 Endergonic reactions require energy to
proceed.
 Coupling an energy-requiring reaction with an
energy-yielding reaction can drive endergonic
reactions.
 ATP is the most common intermediate in
coupled reactions.
Importance of ATP
 ATP consists of
adenosine (adenine
+ ribose) and a
triphosphate group.
 The bonds between
the phosphate
groups are high
energy bonds.
 A-P~P~P
Importance of ATP
 Phosphates have
negative charges.
 Takes lots of energy
to hold 3 in a row!
 Ready to spring
apart.
 So, ATP is very
reactive.
Importance of ATP
 A coupled reaction
is a system of two
reactions linked by an
energy shuttle – ATP.
 Substrate B is a fuel
– like glucose or lipid.
 ATP is not a
storehouse of energy
– used as soon as
it’s available.
Cellular Respiration
 Cellular respiration – the oxidation of food
molecules to obtain energy.
 Electrons are stripped away.
 Different from breathing (respiration).
Cellular Respiration
 Aerobic versus Anaerobic Metabolism
 Heterotrophs
 Aerobes: Use molecular oxygen as the final
electron acceptor
 Anaerobes: Use other molecules as final electron
acceptor
 Energy yield much lower ATP yield
Cellular Respiration
 When oxygen acts as the final electron
acceptor (aerobes):
 Almost 20 times more energy is released than if
another acceptor is used (anaerobes).
 Advantage of aerobic metabolism:
 Smaller quantity of food required to maintain
given rate of metabolism.
Aerobic Respiration
 In aerobic respiration, ATP forms as electrons are
harvested, transferred along the electron transport chain
and eventually donated to O2 gas.
 Oxygen is required!
 Glucose is completely oxidized.
 C6H12O6 + 6O2
Glucose
Oxygen
6CO2 + 6H2O + energy (heat
or ATP)
Carbon
Water
Dioxide
Cellular Respiration - 3
Stages
 Food is digested to break it into
smaller pieces – no energy
production here.
 Glycolysis – coupled reactions
used to make ATP.
 Occurs in cytoplasm
 Doesn’t require O2
 Oxidation – harvests electrons
and uses their energy to power
ATP production.
 Only in mitochondria
 More powerful
Anaerobic Respiration
 Anaerobic respiration occurs in the absence
of oxygen.
 Different electron acceptors are used instead of
oxygen (sulfur, or nitrate).
 Sugars are not completely oxidized, so it doesn’t
generate as much ATP.
Glycolysis
 Glycolysis – the first stage in cellular
respiration.
 A series of enzyme catalyzed reactions.
 Glucose converted to pyruvic acid.
 Small number of ATPs made (2 per glucose
molecule), but it is possible in the absence of
oxygen.
 All living organisms use glycolysis.
Glycolysis
 Uphill portion primes the fuel
with phosphates.
 Uses 2 ATPs
 Fuel is cleaved into 3-C
sugars which undergo
oxidation.
 NAD+ accepts e-s & 1 H+ to
produce NADH
 NADH serves as a carrier to
move high energy e-s to the
final electron transport chain.
 Downhill portion produces 2
ATPs per 3-C sugar (4 total).
 Net production of 2 ATPs per
glucose molecule.
Glycolysis
 Summary of the enzymatically catalyzed
reactions in glycolysis:
Glucose + 2ADP + 2Pi + 2 NAD+
2ATP
2 Pyruvic acid + 2 NADH +
http://www.youtube.com/watch?v=3GTjQTqUuOw&list=FL9N_Px072WuVorSwDfqf-9w&index=4&feature=plpp
Harvesting Electrons form
Chemical Bonds
 When oxygen is available, a second oxidative
stage of cellular respiration takes place.
 First step – oxidize the 3-carbon pyruvate in the
mitochondria forming Acetyl-CoA.
 Next, Acetyl-CoA is oxidized in the Krebs cycle.
Producing Acetyl-CoA
 The 3-carbon pyruvate
loses a carbon producing
an acetyl group.
 Electrons are transferred
to NAD+ forming NADH.
 The acetyl group
combines with CoA
forming Acetyl-CoA.
 Ready for use in Krebs
cycle.
The Krebs Cycle
 The Krebs cycle is the next stage in oxidative
respiration and takes place in the mitochondria.
 Acetyl-CoA joins cycle, binding to a 4-carbon molecule
to form a 6-carbon molecule.
 2 carbons removed as CO2, their electrons donated to
NAD+, 4-carbon molecules left.
 2 NADH produced.
 More electrons are extracted and the original 4-carbon
material is regenerated.
 1 ATP, 1 NADH, and 1 FADH2 produced.
The Krebs Cycle
 Each glucose provides 2 pyruvates, therefore 2
turns of the Krebs cycle.
 Glucose is completely consumed during
cellular respiration.
The Krebs Cycle
Acetyl unit + 3 NAD+ + FAD + ADP + Pi
NADH + FADH2 + ATP
http://www.youtube.com/watch?v=-cDFYXc9Wko
2 CO2 + 3
Using Electrons to Make ATP
 NADH & FADH2
contain energized
electrons.
 NADH molecules carry
their electrons to the
inner mitochondrial
membrane where they
transfer electrons to a
series of membrane
bound proteins – the
electron transport
chain.
Building an Electrochemical
Gradient
 In eukaryotes, aerobic metabolism takes place
in the mitochondria in virtually all cells.
 The Krebs cycle occurs in the matrix, or
internal compartment of the mitochondrion.
 Protons (H+) are pumped out of the matrix into
the intermembrane space.
Electron Transport Review
http://www.youtube.com/watch?v=kN5MtqAB_Yc&list=FL9N_Px072WuVorSwDfqf-9w&index=2&feature=plpp
Review of Cellular Respiration
 1 ATP generated for each proton pump
activated by the electron transport chain.
 NADH activates 3 pumps.
 FADH2 activates 2 pumps.
 The 2 NADH produced during glycolysis must
be transported across the mitochondrial
membrane using 2 ATP.
 Net ATP production = 4
Glucose + 2 ATP + 36 ADP + 36 Pi + 6 O2
6CO2 + 2 ADP + 36 ATP + 6 H2O
Metabolism of Lipids
 Triglycerides are broken down into glycerol and
3 fatty acid chains.
 Glycerol enters glycolysis.
 Fatty acids are oxidized and 2-C molecules
break off as acetyl-CoA.
 Oxidation of one 18-C stearic acid will net 146 ATP.
 Oxidation of three glucose (18 Cs) nets 108 ATP.
 Glycerol nets 22 ATP, so 1 triglyceride nets 462 ATP.
Metabolism of Proteins
 Proteins digested in the gut into amino acids
which are then absorbed into blood and
extracellular fluid.
 Excess proteins can serve as fuel like
carbohydrates and fats.
 Nitrogen is removed producing carbon skeletons
and ammonia.
 Carbon skeletons oxidized.
Metabolism of Proteins
 Ammonia is highly
toxic, but soluble.
 Can be excreted by
aquatic organisms
as ammonia.
 Terrestrial
organisms must
detoxify it first.
Cell differentiation and regeneration
Red and white blood cells in a large vessel
The number of cells
from any organism
ranges from one to
trillions.
However, even the
most complex
organisms have a
relatively small (~200)
catalog of
differentiated cell
types with specialized
function (bone,
muscle, nerve).
Cell differentiation: the process by which an undifferentiated cell reaches
its specialized function. It occurs during histogenesis. Cell differentiation
is stable. Most differentiated cells cannot transform into other cell types (it
can happen during regeneration).
Cell division and differentiation
Cell differentiation occurs continuously in adult organisms. Most organisms
live much longer than the individual cells from which they are composed. As
cells die, new cells differentiate for replacement.
The rate of cell turnover differs dramatically in different tissues. The lining of
the small intestine is completely replaced every few days. However, neurons
are long lived and don’t recycle.
Differentiated cells are produced by 2 methods:
1. Some differentiated cells
divide. Hepatocytes are liver
cells that make bile and detoxify
chemicals. They are long lived
and divide slowly.
However, after damage by
toxins or injury, hepatocytes
grow rapidly. If you remove 2/3
of the liver, it regenerates in 1-2
weeks.
Stem cells
2. Other differentiated cells arise from a pool of undifferentiated stem cells.
Stem cells have 3 properties:
1.
2.
3.
They are undifferentiated.
They have a capacity for self
renewal and divide slowly.
They form committed progenitor
cells that divide a few times but are
committed to form a specific tissue.
Renewal by stem cell differentiation is
common (blood cells, epithelia, and
spermatogonia).
Stem cells are usually hidden in a safe,
sequestered site away from injury. Stem
cells of the intestine lie at the base of
the Crypts. They continuously release
committed progenitor cells that form
the intestinal villi.
Differentiation of blood cells
Hematopoiesis: (hemat = blood, poien = to make), the blood of vertebrates
contains many different types of cells with distinct functions. All mature
blood cells are short lived and must be replaced continuously from stem
cells. In humans, the hematopoietic stem cells produce billions of blood
cells each hour to replace the aging cells.
Hemangioblast: an embryonic stem cell that gives rise to blood vessels
and universal blood stem cells.
Universal blood stem cells: form myeloid and lymphoid precursors.
Myeloid precursors form several types of differentiated cells including red
blood cells which transport O2 and CO2. They also make platelets for
coagulation of blood, and monocytes / granulocytes that serve a protective
role.
Lymphoid precursors make lymphocytes that are involved in B and T cell
immunity.
The overall scheme for
hematopoiesis.
The embryonic stem cell,
the hemangioblast, gives
rise to angioblasts that
make both vessels and
universal blood stem cells.
The universal stem cells
renew and also form the
myeloid and lymphoid
precursors.
How is hematopoiesis regulated?
Blood cells and vessels are derived from mesoderm. BMP-4 is a protein that
promotes ventral development. It combines with other cytokines including
fibroblast growth factor and activin to induce hematopoesis.
The SLC gene was discovered as over
expressed in human leukemia, and it
appears to be required early in the process
of stem cell development. Knock out the
gene in mice = they fail to form blood cells.
Pluripotent stem cells and progenitor cells
express transcription factors/switch genes
that direct pathways of differentiation.
GATA proteins regulate the decision to form
progenitors or remain as stem cells.
GATA-1 induces RBCs. GATA-2 blocks RBC
differentiation and induces stem cells.
Colony stimulating factors (CSF-1) are
cytokines that direct expression of specific
transcription factors for myeloid cells.
Erythrocytes mature in bone marrow from precursors called erythroblasts.
Step 1: erythrocyte burst-forming cell forms
from the myeloid stem cells and can make up
to 5000 erythrocytes (red blood cells) if the
CSF IL-3 is present.
Step 2: the burst-forming cells respond to
another CSF known as erythropoietin, which
controls the total number of divisions.
More erythropoietin is made when a person
requires more O2. For example, when one is
high above sea level or sick with anemia.
The erythroblast is filled with hemoglobin and
loses organelles including the nucleus to form
the mature red blood cell.
Billions of old red blood cells are removed
from the blood each day by apoptosis
(programmed cell death) and must be replaced.
Genetic control of muscle cell differentiation
Myo D is a master regulator of muscle cell differentiation. If you inject
Myo D DNA into a fibroblast it turns into a muscle cell. It is a member of a
myogenic family (Myo D, myogenin, myf-5, and MRF-4).
These are transcription factors (basic helix-loop-helix) and activate genes
that are needed for muscle cell differentiation.
The basic region binds to DNA, the HLH region causes dimer formation with
other HLH proteins such as E proteins = induces muscle differentiation.
Another member of the HLH family is id. This is an inhibitor of
differentiation. It has the HLH domain but there is no basic region to bind
DNA. It binds to other HLH proteins and blocks their function = prevents
muscle cell differentiation.
Knock out mice have confirmed the importance of these genes in muscle
cell differentiation. Myo D- / myf-5- mice die after birth due to a lack of
skeletal muscle. Myogenin– mice also die at birth due to disorganized
muscle fibers (fibers are not aligned and don’t work properly).
Adult stem cells have unexpected potency
Recently, it was discovered that adult stem cells can produce a variety of
differentiated cell types. They are not limited to the cell types in the tissue
from which they are derived.
Ependymal cells line the fluid
filled ventricles of the brain
and appear to be stem cells.
When mouse neural stem cells
are injected into the
bloodstream, they form
myeloid cells and
lymphocytes. The injected
cells were labeled with a
reporter gene for b-galacto
sidase so they could be
distinguished from host cells.
Stem cells from bone marrow
can give rise to a variety of
tissues such as liver,
adipocytes, and chondrocytes.
Medical importance
The ability of stem cells to multiply and produce a wide range of differentiated
cell types is potentially of great medical importance.
When signals that direct stem cell differentiation become better understood, it
may be possible to use the cells to replace damaged or diseased tissue.
Examples include Alzheimer’s disease, Parkinson’s disease, loss of brain
tissue after stroke or injury, inducing b cells to treat diabetes, and restoring
cartilage that is damaged by arthritis.
Human embryonic stem cells are particularly interesting. They are found in the
inner cell mass of the early blastula. They divide infinitely and produce many
types of differentiated cells.
In the future, it may be possible to clone the cell of a patient who has suffered a
heart attack. This could be used to create a blastocyst by nuclear transfer to an
oocyte. Stem cells from the inner cell mass could be harvested and induced to
form cardiac muscle. These could be transplanted into the patient’s heart
muscle to repopulate the scar.
Currently, research with embryonic stem cells is not funded by the US
government, and political issues prevent rapid progress in this area by US
scientists.
Recent work has questioned the value of adult stem cells
Over the past two years, evidence has mounted that adult cells may be
almost as malleable as embryonic cells. For example, blood precursor cells
can form other tissues, such as brain cells, if they are first incubated with
embryonic stem cells.
Several recent studies (within the last several months) have raised doubts
about the validity of those results. Rather than switching their fate — a
phenomenon known as transdifferentiation — the adult cells might actually
be fusing with the embryonic cells to become an entirely new type of cell.
Fused cells might be too abnormal to be of medical use.
The fusion argument is likely to come up in the Senate in debates there
over a bill introduced by Sam Brownback (Republican, Kansas) that would
ban human cloning. The nuclear-transfer procedure used in cloning could
also be used to produce genetically compatible embryonic stem cells for
treating disease in individual patients. Therapeutic cloning versus
reproductive cloning of new individuals.
Brownback has argued that adult stem cells make this unnecessary, as
they can be taken directly from the patient.
Regeneration
Many animals have an extraordinary ability to regenerate body structures
(starfish or newts). There are 2 basic types of regeneration:
Epimorphosis: characteristic of regenerating limbs. It is characterized by
dedifferentiation of remaining tissue, increased cell division to make more
tissue, and differentiation into all of the cell types that are needed.
Morphallaxis: occurs exclusively through repatterning of tissues and requires
no new cell division. Often makes a smaller structure.
Epimorphic regeneration
How does regeneration work in salamanders? When a limb is amputated, the
remaining cells construct a new limb to exactly match the previous one.
After amputation a plasma clot forms. Adjacent cells migrate to cover it and
form an apical ectodermal cap. In contrast to mammals, no scar forms.
Cells beneath the cap dedifferentiate (bone, muscle, blood) and detach from
one another. The mass of unifferentiated cells is a regeneration blastema.
The undifferentiated cells proliferate
and resemble the progress zone of a
growing embryonic limb. There is a
similar pattern of Hox gene expression
and growth factor expression
including FGF and SHH.
Retinoic acid is produced by the
blastema and specifies the proximal
position on which to build. Too much
retinoic acid causes excess limb
growth.
Morhallactic regeneration
Hydra is a small fresh water organism
with a tube body, a hypostome (head
region), and a basal disc (foot). These
organisms can produce sexually, but
they usually multiply by budding.
When a hydra is cut in half, both ends
regenerate a new body. If a slice is cut
out of the middle, both ends
regenerate a hypostome and foot.
However, there is no cell growth, so
the organism will be much smaller.
The remaining cells simply reorganize
to form a new, smaller hydra.
Medical advances in regeneration
Humans can regenerate some tissues (liver,
peripheral nerve). Children even retain the ability to
regenerate finger tips. However, most tissues cannot
be regenerated. The ability to regenerate human
tissue would be a major medical breakthrough.
Bone regeneration: bone heals but it can’t regenerate
to fill in a gap. A new technique involves grafting a gel
containing parathyroid hormone. This stimulates
bone regeneration and is used successfully in dogs.
Nerve regeneration: CNS has no ability to regenerate
neurons but peripheral nerves do. When an axon of a
peripheral nerve is cut, the remaining cell
regenerates. This follows the Schwann cells (cells
that insulate axons) to find the proper synapse.
When the spinal cord is damaged, oligodendrocytes
release factors that block axon regeneration leading
to permanent paralysis. Two genes, Nogo-1 and MAG,
are responsible. Antibodies to these proteins support
partial regeneration.