Cell Environment

Question 1

What is function of the mitochondira?

Answer 1

Make ATP

Question 2

What is function of ER/Golgi?

Answer 2

Synthesis membrane and secreted proteins.

Question 3

What is function of lysosomes?

Answer 3

Protease-filled ‘stomach’ of the cell

Question 4

What is the function of vesicles?

Answer 4

Move molecules between compartments

Question 5

Explain the cell wall of bacteria, what breaks it down?

Answer 5

• Rigid cell wall (cannot change shape, but are strong)
• Made of polysaccharide cross linked with peptides, protects bacteria in the body

However:

• Penicillin blocks the transpeptidase
• Lysozyme digests the polysaccharide

Question 6

Animal cells have a cytoskeleton; how is this different to bacteria?

Answer 6

Cytoskeleton is inside the cell and provides structure and shape (which can change). However is is more fragile than bacteria, as it only has the phosobilipid layer protecting the cell.

Question 7

What are cytoskeletons made of? Explain them.

Answer 7

Protein polymers.

INTERMEDIATE filaments are rope-like and give mechanical strength to cells (rigid cell shape).

ACTIN filaments are helical polymers of actin protein; they give dynamic cell shape and movement.

MICROTUBULES are hollow polymers of tubulin protein; they are a framework for moving objects within a cell.

Question 8

What is a desmosome?

Answer 8

Connect epithelial cells together

Question 9

What is a hemidesmosome?

Answer 9

Connect epithelial cells to the underlying extracellular matrix.

Question 10

What are keratin filaments?

Answer 10

Intermediate filaments. In epithelial cells they span the cell forming a framework which supports the cell and links it mechanically to neighboring cells.

Question 11

What is “junctional epidermolysis bullosa (JEB)? A intermediate filament genetic disorder.

Answer 11

It is a genetic disease which reduces the function of keratin intermediate filaments in the skin. Defective keratin network results in skin tearing (dying) rather than distributing stress evenly and protecting the skin.

In horses “Red Foot Disease” or “Hairless Foal Syndrome”.

12% of Belgian Draft Horses carry the trait. Seen rarerly in dogs, sheep and cattle.

First signs are blistering of gingiva and tongue on nursing; followed by blistering of skin and shedding of hooves.

No treatment, however thoughtful breeding can prevent the disease passing to foals.

Question 12

What is the structure and function of actin filaments?

Answer 12

• Small globular proteins form a double helical structure.
• Bad strength (breaks easily) though very dynamic.
• 50:50 split of free and formed actin filaments

Protrusion and contraction:

• Cell moves (protrusion) by de and re polymerising actin filiaments.
• Cell contracts (back end of cell when moving) with myosin to contract.
• function in: cell migration, phagocytosis, cytokinesis

Mechanical support for the membrane:

Actin filaments form a mesh between plasma membrane, linked together by proteins (spectrin), providing strength (particularly red blood cells).

Question 13

What is the structure and function of microtubules?

Answer 13

A network to move stuff around.

Polymer of small tubulin monomers forming a hollow tube.

Grow from centre of the cell (MTOC) and radiate outwards to plasma membrane, connected to all organelles through motor proteins.

Constantly reaching out, retracting and then re positioning.

Question 14

Explain microtubule cytoskeleton rearrangement in mitosis?

Answer 14

1. MTs depolymerise
2. MTOC divides to form two centrosomes
3. MTs grow, forming mitotic spindle
4. Some attach to chromosome pairs, some overlap and hold spindle together
5. Astral MTs orientate and position the spindle in the centre
6. Motor proteins interact with spindle to regulate shape and position of chromosomes

Question 15

What is the structure and function of intermediate filaments?

Answer 15

• Rope like bundles.
• monomers (elongated) become dimers (head-to-head).
• Dimers form tetramers (head to tail) creating rope-like filaments.

Very strong, stable and insoluble.

Question 16

Reference a actin cytoskeleton genetic disease.

Answer 16

Mechanical support: Genetic disease “sperocytosis” rare in animals,
A defect in sprectrin (protein linking together actin filaments).
Shape of RBC spherical, leads to anemia.

Question 17

Why do microtubule cytoskeletion have to function prefectly in cytokinesis?

Answer 17

The MTs arrange the chromosomes, attaching the correct one to the correct tubucle.
If the MTs don’t get all, or they go to the wrong side,
then there are chromosomal abnormalities and genomic instability.

MTs separate chromosomes during mitosis, but also play a critical role in testing that the process will work before it happens.

Question 18

What is the basic structure and function of collagen?

Answer 18

Three separate protein chains, wound around each other to make a triple helix.
Interactions between the chains gives it great strength.
There are 26 different types of collagen. Its function is to provide mechanical strength.

Question 19

What are the roles of vitamin C in collagen processing?

Answer 19

Vitamin C is the cofactor for hydroxylase enzymes.

Hydroxyproline interactions strengthen links between collagen chains.

Question 20

Is Vitamin C an essential vitamin in all animals?

Answer 20

Most animals can make Vitamin C from glucose in their liver or kidney (Humans and animals cannot).

Question 21

What is the link between genetic disease and correct collagen processing?

What is dermatosparaxis and Ehlers-Danlos syndrom?

Answer 21

A defect in collagen processing is “dermatosparaxis” (torn skin). Affects procollagen peptidase gene; propeptide ends are not cut off properly, impairing fibril formation (weak skin).

Seen in white dorper breed of (sheep). It has a thick skin and is suited to arid conditions. Selective breeding can be implemented to remove dematosparaxis mutation.

Ehlers-Danlos system is a defect in fibre formation.
In dogs: skin is unusually elastic. Joints are lax, can be bent further without pain. Animal can have fine white scars and an unhealable split in the skin.

Question 22

What is the function and purpose of lysine in collagen?

Answer 22

The amount of lysine in collagen is only 3 or 4% of total amino acids, but it has an important function in the constitution of the cross-links between the molecules to built the fibrils and the fibers of collagen. For this function, some lysine molecules must be hydroxylated.

Question 23

How is collagen is modified? What is the process?

Answer 23

Hydroxylation (the addition of an -OH group).
Collagen proteins contain many repeating “Gly-Pro-X” motifs.
Prolines are converted to hydroxyproline by enzyme prolyl hydroxylase.
Lysines are converted to hydroxylysine by enzyme lysyl hydroxylase.

Glycosylation: Hydroxylysine groups modified with addition of carbohydrates.
Collagen peptides assemble into procollagen triple helix
Collagen peptidase cuts off the propeptide ends
Lysly oxidase form strong covalent bonds between lysines in adjacent chains.

Collagen then assembles into fibrils, which then organise into fibres.
In tendon, these form a highly organised array that gives strength to the tissue.
In skin, collagen is arranged in different angles. Different mechanical properties result from different arrangement of the fibres.

Question 24

What are the consequences of a vitamin C deficiency?

Answer 24

Scurvy.
Weakened collagen structure as hydroxyprolines are not formed.
Sore gums, loose teeth, sores, swollen joints, rough coat.

Question 25

How do secreted proteins travel in the cell?

Answer 25

Proteins for secretion are synthesised into ER and travel in vesicles to the Golgi for glycosylation (addition of carbohydrate). Further vessicles transport proteins to the plasma membrane.

Question 26

How are secretory vesscles release?

Answer 26

Constituently (constant) or in the case of hormones, they are released on demand (regulated).

Question 27

How to epithelial cells secrete milk into mammary glands?

Answer 27

Golgi produces protein casein and sugar lactose. They travel in same vesicle and are secreted by epithelium into central luman. Fat is produced on the smooth ER (no ribosomes) and released into lumen.

Question 28

How does milk come out of the glands?

Answer 28

Myoepithelial cells surround epithelial cells contract (actin and myosin filaments) causing expulsion of milk.

Question 29

What is the purpose and function of propetide ends?

Answer 29

Propeptide ends prevent formation of collagen fibres. They're cleaved outside cell by peptidase which leads to self-assembly into collagen fibrils.

Question 30

Summarise the 9 steps of collagen processing

Answer 30

1. Synthesis of pro-alpha chain 2. Hydroxylation of selected prolines and lysines 3. Glycosylation of selected hydroxylysines 4. Self-assembly of three pro-alpha chains 5. Procollagen triple-helix formation 6. Secretion via vesicle 7. Clevage of propetides by peptidase 8. Self-assembly into fibril 9. Aggreation of collagen fibrils to form collagen fibre

Question 31

Summarise the 9 steps of collagen processing

Answer 31

1. Synthesis of pro-alpha chain 2. Hydroxylation of selected prolines and lysines (add -OH) 3. Glycosylation of selected hydroxylysines (add carbohydrate) 4. Self-assembly of three pro-alpha chains 5. Procollagen triple-helix formation 6. Secretion via vesicle 7. Clevage of propetides by peptidase 8. Self-assembly into fibril 9. Aggreation of collagen fibrils to form collagen fibre

Question 32

What is the composition of bone and cartilage, what cells are involved in making them?

Answer 32

Type I collagen (35%) - elasticity Hydroxyapatite (65%) mineral content, calcium - strength Cartilage: Type II collagen (smooth), proteoglycans (bouncy, cushion). Cells involved: chondroblasts/chondrocytes, secrete type II collagen and proteoglycans. Form cartilage template in shape of final bone. Caritlage remains at smooth service of articulated joints. Chondroblasts eventually become surrounded by ECM and differentiate into chrondrocytes. osteoblasts, Secrete Type I collagen and calcium and phosphate to mineralise the bone. osteoclasts. Secreate proteases and acid to break down bone. Seal themselves to the bone surface, forming a digestive zone. Required for bone remodelling - a constant process.

Question 33

How do long bones grow in development, what is the function of the growth plate?

Answer 33

1. Formation of bone collar around hyaline cartilage template. 2. Cavitation of the hyaline cartilage within the template; primary ossification centre enlargens 3. Spongey bone formation, blood vessel of periosteal bud 4. Formation of the medulla cavity as primary ossification continues. Appearance of the secondary ossification centre in the epiphyses. 5. Ossification of the epiphyses. When complete, hyaline cartilage remains only at arthro surface and in epiphyseal plates (growth plates). Growth plate function is to elongate the long bones in juvenile animals. Chondroblasts and osteoblasts continue to create cartilage and convert into bone, continuing into puberty, terminated by the onset of sex hormones estrogen and testosterone (which switches off the process) and minerlises the growth plates into bone, and bone length is fixed forever.

Question 34

How do Osteoblasts make bone matrix?

Answer 34

Osteoblasts attach to the ECM produced by chondrocytes, and secrete collagen type I, forming tough fibres called osteoid, which provide the elastic strength of bone. Osteoblasts also secrete vesicles containing calcium and phosphate into the extracellular space, bursting open and become seed sites for the formation of hydroxyapatite (and insoluble calcium salt) Ca10(PO4)6(OH)2.

Question 35

How does chondrodysplasia affect animal size?

Answer 35

Extra copy of FGF4 gene. Converts growth place to bone too fast, limiting growth. Affects daschunds, corgis, bulldogs. As age, predisposition to osteoarthritis, particularly spinal arthritis. Normal size head and body, though legs are shorter as they stop growing earlier than other dogs. A second cause can arise from mechanical shock to the bone (Injuries when puppies should be avoided) German shepherds and Malamutes can arise from new (or recessive) mutations.

Question 36

What are the role of osteoclasts in remodelling bone?

Answer 36

Osteoclasts degrade bone (controlled). H+ and Cl- secrete into the sealing zone (bound by integrin interactions). Lysososomes inside the osteoclast fuse with plasma membrane and release protease (to digest protein content of bone collagen). The ruffled border with increased surface area absorbs phosphate and calcium ions and amino acids from bone digestion for use elsewhere.

Question 37

How does the repair of fractures reactive pathways of bone development?

Answer 37

Bone repair involves all three cell types. 1. Chondrocytes activate to secrete new cartilage into fracture site. 2. Osteoblasts secrete new bone onto cartilage to form callus 3. Osteoclasts remodel the callus to remove excell bones 4. Osteoblasts remodel the callus bone to make stronger, woven bone.

Question 38

What is the clinical relevance of disuse osteoperosis?

Answer 38

Mechanical stress stimulates osteoblasts and inhibits osteoclasts. Immodilisation leads to osteoprosis. Bone density occurs due to lack of mechanical loading (stimulation of osteoclasts and inhibiton of osteoblasts. Laying hens: Calcium balance affects bone density. Laying hens calcium store for egg shell production is the medullary (centre) bone. Thus, old cage systems, inactivity and high egg yield triggered onset of osteoperosis and accounted for 30% mortality "cage layer fatigue".

Question 39

How do Osteoblasts make bone matrix?

Answer 39

Osteoblasts attach to the ECM produced by chondrocytes, and secrete collagen type I, forming tough fibres called osteoid, which provide the elastic strength of bone. Osteoblasts also secrete vesicles containing calcium and phosphate into the extracellular space, bursting open and become seed sites for the formation of hydroxyapatite (and insoluble calcium salt).

Question 40

What determines the overall mechanical properties of a bone?

Answer 40

Collagen:mineral. More collagen = more elastic More mineral = more strength

Question 41

How is bone density controlled?

Answer 41

A balance of osteoblast and osteoclast activity. Mechanical stress stimulates osteoblasts and inhibits osteoclasts. Parathyroid hormone is the major controller of blood calcium levels in mammals, increasing osteoclast activity leading to loss of bone density. Calcitonin antagonises PTH by decreasing osteoclast activity and inhibiting the production of new osteoclasts. Vitamin D increases bone re absorption by increasing osteoclast number, but also promotes calcium uptake in the intestine. Oestrogen inhibits osteoclast activity and promotes osteoblast activity. Exposes women post menopause to osteoperosis.