1. Cellular Metabolism

2. 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”

3. 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 lungs where you exhale them

4. During metabolism, energy is both used and produced
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

5. 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

6. Catabolism and Anabolism
Catabolic Reaction (glycogen breaks down, which releases energy)
Glycogen
Glucose
ENERGY
Anabolic Reaction (glycogen is created, which takes energy)
Glycogen
ENERGY
Glucose
Glucose

7. 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

8. Storing Energy – Energy is stored when a third phosphate group bonds to ADP, forming ATP
Using Energy – When a cell needs energy, a phosphate bond in ATP breaks, release energy and produces ADP and separate phosphate group
ENERGY P P P A P P P A

9. 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

10. 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

11. 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 % of the US population is considered overweight (I am sure it’s higher now)

12. Questions How is metabolism related to homeostasis?
Describe an environment in which metabolism can occur.
How do humans get energy?
How are carbohydrates metabolized?
How are anabolism and catabolism related?
How is energy transferred from nutrients to the body’s cells?

13. Questions Continued How does a body maintain its supply of ATP?
Why is osmosis necessary for metabolism?
Why is your metabolic rate different from an alligator’s?
How does your metabolic rate compare to small animals?
Do you use energy while sleeping? – Explain.
How will your body respond if you start skipping meals?
How can you prevent lactic acid buildup? Why do these techniques work?

14. Cellular Metabolism
Cellular metabolism refers to all of the chemical processes that occur inside living cells.

15. 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.

16. Energy
The ultimate source of energy for most living things is the sun.

17. 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

18. 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.

19. 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.

20. 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.

21. Enzymes
Enzymes may be pure proteins or proteins plus cofactors such as metallic ions or coenzymes, organic group that contain groups derived from vitamins.

22. 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.

23. 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

24. 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.

25. 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.

26. Cellular Respiration
Cellular respiration – the oxidation of food molecules to obtain energy.
Electrons are stripped away.
Different from breathing (respiration).

27. 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

28. 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.

29. 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 6CO2 + 6H2O + energy (heat Glucose Oxygen Carbon Water or ATP)
Dioxide

30. 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

31. 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.

32. 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.

33. 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.

34. Glycolysis
Summary of the enzymatically catalyzed reactions in glycolysis:
Glucose + 2ADP + 2Pi + 2 NAD Pyruvic acid + 2 NADH + 2ATP

35. 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.

36. 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.

37. 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.

39. The Krebs Cycle
Each glucose provides 2 pyruvates, therefore 2 turns of the Krebs cycle.
Glucose is completely consumed during cellular respiration.

40. The Krebs Cycle
Acetyl unit + 3 NAD+ + FAD + ADP + Pi 2 CO NADH + FADH2 + ATP

41. 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.

42. 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.

43. Electron Transport Review

44. 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

45. Glucose + 2 ATP + 36 ADP + 36 Pi + 6 O2 6CO2 + 2 ADP + 36 ATP + 6 H2O

46. 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.

47. 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.

48. Metabolism of Proteins
Ammonia is highly toxic, but soluble.
Can be excreted by aquatic organisms as ammonia.
Terrestrial organisms must detoxify it first.

49. 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).

50. 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.

51. Stem cells
2. Other differentiated cells arise from a pool of undifferentiated stem cells.
Stem cells have 3 properties:
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.

52. 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.

53. 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.

54. 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.

55. 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.

56. 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.

57. 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).

58. 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.

59. 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.

60. 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.

61. 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.

62. 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.

63. 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.

64. 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.