systems to cells 1-5

Question 1

examples of energy dependent proccesses

Answer 1

1. Active transport (sodium/potassium pump)
2. muscle contraction
3. cellular respiration
4. protein synthesis
5. photosynthesis

Question 2

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why is glucose a good energy source

Answer 2

1. high energy content
2. solubility in water
3. as it undergoes complete oxidation
4. produces 36-38ATP molecules per glucose during aerobic respiration
5. can easily reserve it by storing it in the form of glycogen.

Question 3

how glucose is metabolised

Answer 3

1. gluocse is broken down into two molecules of pyruvate during glycolysis
2. this generates a net gain of 2ATP and 2NADH.
3. In aerobic conditions, glucose enters mitochondria and is converted into acetyl-Co-A which then enters citric acid cycle.
4. This cycle produces more NADH and FADH2 by oxidizing acetyl-Co-A, releasing C02 as a byproduct.
5. In oxidative phosphorylation, via electron transport chain, NADH and FADH2 donate electrons to produce lots of ATP and water.
6. under anaerobic conditions, pyruvate is converted to lactate.

Question 4

what has an absoloute requirement for glucose for energy

Answer 4

brain and nerves have an absolute requirement for glucose, if levels are too low brain begins to die.

Question 5

how and where glucose is stored as glycogen

Answer 5

1. glucose is stored as glycogen primarily in the liver and muscle cells.
2. glucose is converted into glycogen by glycogenesis.
3. when gluocose levels are high(after eating) insulin signals the cells to take up glucose.
4. An enzyme called glycogen synthase help convert glucose to glycogen
5. glycogenolysis is when glycogen isd converted back to glucose when needed(hunger)
6. the liver can break down glycogen and release glucose into blood stream to maintain levels.
7. glycogen is used directly within muscle cells.
8. important in liver for brain function
9. important in muscles for exercise energy

Question 6

what is hyperglycaemia and hypoglycaemia

Answer 6

hyperglycemia= high blood glucose (above normal)
hypoglycemia = low blood glucose (below normal)

Question 7

how carbohydrate metabolism is controlled at multiple levels

system/tissues/cells

Answer 7

1. systemic level = hormone regulation -> insulin and glucagon actions
2. tissue level = the role of organs (brain, muscles, liver)
3. cellular level = enzyme and transporter regulation -> hexokinase/glucokinase, glucose transporters(GLUT2..)

Question 8

discuss the contrasting roles of insulin and glucagon in blood glucose homeostasis

Answer 8

blood sugar levels are kept constant by a range of homeostatic mechanisms
1. insulin is released by the pancreatic b-cells when blood glucose levels are high. Lowers blood gluocose by promoting glucose uptake by fat and muscle cells where it is stored as glycogen, and inhibits glucose production in the liver.
2. Glucagon is released from pancreatic a-cells when blood glucose levels fall, raises blood glucose by stimulating glycogen breakdown and glucose production in the liver.

these proccesses keep glucose within the healthy range

Question 9

outline the effects of lowering or raising blood glucose on the b-cells of the pancreas and the liver

Answer 9

1. when blood glucose drops, pancreatic b-cells reduce insulin release and the liver when prompted by glucagon, increases glycogen breakdown and glucose productio to raise levels.
2. when blood glucose rises, pancreatic b-cells increase insulin secretion, promting the liver to store glucose as glycogen, and reduce glucose production, lowering levels.

Question 10

explain the role of glycogen

Answer 10

1. primary storage form of glucose
2. ensures body has a continueous supply of glucose

Question 11

what is gluconeogenesis

Answer 11

process that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate or amino acids
- glucagon stimulates this
- insulin inhibits it in the liver

Question 12

compare the flow of glucose to glycogen in the fed and fasted state

Answer 12

1. in the fed state = glucose directed towards glycogen storage, insulin facilitating proccess.
2. in fasted state = glycogen is broken down to glucose, glucagon facilitating the process.

Question 13

the pathway from glucose to glycogen

Answer 13

1. glucose is converted to glucose-6-phosphate by the enzyme hexokinase.
2. glucose-6-phosphate is converted into glucose-1-phosphate by the enzyme phosphoglucomutase (reversible step)
3. Glucose-1-phosphate is converted to glycogen by glycogen synthase(irreversible).
4. glycogen can be converted back to glucose-1-phosphate by glycogen phosphorylase (irreversible).

step 3 and 4 are very different, when one process is active the other on

Question 14

explain metabolic pathway flux, and the role of a regulatory enzyme in such a pathway

Answer 14

1. metabolic pathway flux = the rate at which substates flow through a metablic pathway, shows how effiecient the pathway is in converting reactants to products.
2. enzymes can control this flux by = changing activity, changing location or changing the rate of biosynthesis/degradation levels.

Question 15

Using the examples of Glycogen Synthase and Glycogen phosphorylase, contrast the actions of insulin and glucagon on glycogen synthesis.

Answer 15

1. in the presence of insulin, glucose-1-phosphate to glycogen by the enzyme glycogen synthase is turned on, glycogen back to glucose-1-phosphate by glycogen phosphorylase is turned off.
2. in the presence of glucagon, glucose-1-phosphate to glycogen is turned off and glcogen to glucose-1-phosphate is turned on

both are energetically favourable

Question 16

Explain what is meant by reversible covalent modification of an enzyme, and why it is important. Define ‘kinase’ and ‘phosphatase’.

Answer 16

1. reversible covalent modification of an enzyme = activity of enzyme is altered by addition or removal of specific chemical groups, most common is phosphorylation
2. important for regulating enzyme activity and allows rapid response to cellular changes
3. kinase = enzyme that catalyses the transfer of a phosphate group from ATP to a specific substrate group. (phosphorylation)
4. phosphatase = enzyme that removes phosphate group from a substrate (dephosphorylation) - reversible

Question 17

two main classes of kinase

Answer 17

1. those that phosphorylate Tyrosine residues
2. those that phosphorylate serine/ threonine residues

Question 18

Explain in outline the potential effects of phosphorylating a protein

Answer 18

1. altered enzyme activity
2. change in protein conformation
3. impact of stability
4. involvement in signalling pathways
5. cell cycle regulation

Question 19

Compare the action of insulin and glucagon on the enzymes involved in glycogen metabolism

Answer 19

1. Insulin = promotes activity of glycogen synthase, reduces activity of glycogen phosphorylase
2. Glucagon = decreases activity of glycogen synthase, increases activity of glycogen phosphorylase

Question 20

List some the action of insulin and glucagon on whole body metabolism

Answer 20

1. insulin = suppresses gluconeogenesis in the liver, turns on glycolysis, causes blood glucose levels to fall
2. glucagon = increases gluconeogenesis in the liver, turns off glycolysis, causes blood glucose levels to rise

Question 21

Explain what is meant by allosteric activation of enzyme activity

Answer 21

1. allosteric activation = effecor molecule binds to an enzyme at the allosteric site. Binding induces a conformational change in enzyme that can increase/inhibit enzyme activity.
2. Allosteric Activators: Increase enzyme activity by stabilizing the active form.
   Allosteric Inhibitors: Decrease enzyme activity by stabilizing the inactive form

Question 22

the rate determing step

Answer 22

is the slowest step of a chemical reaction that determines the speed(rate) at which the overall process proceeds.

Question 23

symptoms and prevalence of diabetes

Answer 23

1. symptoms = increased hunger/thirst, frequent urination,fatigue, unexplained weight loss
2. prevalence = approximately 537 million adults (aged 20-79 years) were living with diabetes in 2021, with projections estimating this number will rise to 643 million by 2030 and 783 million by 2045.

Question 24

contrast type 1 and type 2 diabetes

Answer 24

1. type 1 = caused by destruction of pancreatic b-cells due to an autoimmune process or unknown aetiology. Insulin is not produced. 10% of population have this type.
2. type 2= results from a defect in insulin action, insulin resistence. 90% of population have this type.

risk factors = obesity, age, diet, genetics, lazy

Question 25

process of preproinsulin molecule to final folded insulin

Answer 25

1. preproinsulin = the initial translation product of insulin mRNA, consists of n terminus, signal sequence, peptide B chain, connecting polypeptide, peptide A chain, C terminus. (chains are made up amino acids in varied lengths)
2. the signal sequence is cleaved off by signal peptidase changing preproinsulin into proinsulin.
3. Disulphide bonds form between the A and B chain, removing the connecting polypeptide, forming insulin.
4. A and B chains are parallel to each other.
5. this occurs in endoplasmic reticulum.
6. mature insulin is stored in secretory vesicles until needed.

They ensure that insulin is correctly synthesized, folded, and activated

Question 26

Outline the stages in protein synthesis that lead to the insertion of insulin into the ER.

Answer 26

1. ribosome sees mRNA and starts to read along
2. when signal sequence is identified, ribosome is paused, Translation pause signal.
3. signal sequence is recognised by SRP(signal recognition particle). Grabs the signal sequence.
4. By the SPR receptor, ribosome passed to complex of proteins called Sec61 translocon complex(protein pore).
5. this is a gateway to get insulin into ER lumen
6. translation is now carried on
7. insulin peptide is co-translationally passed through membrane and into cytosol of ER.
8. signal sequence is now cleaved off by singal peptidase complex.

summary: gene transciption , RNA proccessing, mRNA export, translation i

Question 27

Name and explain the functions of SRP,SRP-receptor and Sec61 channel in the ER.

Answer 27

1. SRP = when a ribosome synthesizes a protein, SRP binds to the signal sequence and pauses translation. This helps direct the ribosome to the ER.
2. SPR receptor = protein located in ER-membrane that recognizes the SRP-ribosome complex and can bind to it.
3. Sec61 channel = protein complex that forms a translocation channel in the ER membrane. When ribosome reaches it, translation can continue, allowing polypetide chain to enter the ER lumen.
4. insulin can only fold to active form properly in the lumen of the ER.

Question 28

how ER, Golgi, Endosomes, Vacuoles and the plasma membrane are related/linked.

Answer 28

1. nucleus = where transcription of insulin gene occurs
2. rough ER = Ribosomes attached to the rough ER synthesize preproinsulin, which is then processed in the ER. (site of protein synthesis)
3. golgi apparatus = Proteins from the rough ER are transported to the Golgi apparatus in transport vesicles.
4. secretory vesicles = after golgi, proteins packed in secretory vesicles
5. endosomes = can receive vesicles from membrane and golgi
6. vacuoles = can store substances, receieve materials for degradation
7. plasma membrane = where proteins are secreted

Question 29

trans-golgi network

Answer 29

= is the sorting point where proteins can go to different places eg endosomes, lysosomes

Question 30

insulin in the secretory vesicles

Answer 30

1. once insulin is packaged into vesicles, enzymes can cut out the c peptide from insulin leaving mature insulin.
2. insulin is only released upon presence of a signal (blood sugar increasing)
3. the signal casues vesicles to fuse with the plasma membrane and release their content

Question 31

define regulated exocytosis

Answer 31

the release of hormones from vesicles and fusion with plasma membrane

Question 32

what is glucokinase

Answer 32

adds phosphate onto ADP
1. phosphorylates glucose to glucose-6-phosphate only in b-cells
2. alternative form of hexokinase

Question 33

Explain the steps involved in the regulated release of insulin from beta-cells in response to elevated glucose

summarised

Answer 33

1. glucose uptake by GLUT2 transporters
2. glucose metabolism increases ATP production
3. ADP:ATP ratio increases, closing potassium ATP channels, leading to membrane depolarization
4. calcium channels open, calcium influx from outside to inside the cell
5. calcuim influx triggers the fusion of secretory vesicles with the cell membrane.

Question 34

how does a membane protein move a polar solvent across a non-polar membrane

Answer 34

by the use of transporters = has a hydrophobic side so can interact with the tail of plasma membrane, has a hydrophiilic core that can interact with glucose.
- glucose is a polar molecular and interacts with water so it is surrounded by water
- lower energy input when transporter is used
- glucose transporters are facilitative diffusion transporters.

Question 35

how the structure of a transporter and a channel differ

Answer 35

transporters= mediate the movement of one solute molecule
channels= ‘open’ and allow flow of many ions quickly.

Question 36

consequences of a high Km transporter for glucose in a beta-cell

Answer 36

1. a high Km value indicates a transporter has a low affinity for glucose. only allows glucose to be transported into b-cells when blood glucose levels are elevated.
2. . GLUT2 only efficiently transports glucose into the cell when levels are high, which allows β-cells to gauge blood glucose concentration and respond by secreting insulin.
3. • The cell must be able to sense the extracellular concentration of glucose and adjust intracellular metabolism to the direct proportion of glucose outside the cell.
4. GLUT2= high Km transporter

Question 37

michelis- menten curve

Answer 37

v max= theoretically maximum velocity
1/2 v max= half maximum velocity
Km = measure of affinity of that enzyme for its substrate (high Km, low affinity, vise versa)

Question 38

signal for insulin release

Answer 38

the signal for insulin release is directly proportional to blood glucose levels

Question 39

key targets for insulin

Answer 39

1. muscle(increases glucose uptake for energy)
2. liver (promotes glucose storage as glycogen)
3. fat (store glucose as fat)
   - insulin binds to a specific receptor expressed only on the surface of these tissues

Question 40

structure and function of insulin receptor

Answer 40

1. receptor has 2 alpha(external) and 2 beta subunits(internal), held together by disulphide bonds.
2. insulin binds to alpha subunits, inducing conformational change
3. transmits signal to beta subunits, altering conformation
4. this activates an intrinsic tyrosine kinase domain that initiates signal within the cell

Question 41

what is autophosphorylation

Answer 41

1. adding a phosphate group to itself
2. When insulin binds, it induces autophosphorylation of the receptor’s tyrosine residues in its intracellular domains.

Question 42

Briefly outline the signalling pathway from the insulin receptor to Akt

Answer 42

1. specific ligand binds to specific receptor
2. autophosphorylation of specific tyrosine residues
3. recruits SH2 domain-containing proteins to the receptor
4. different receptors recruit different SH2 domain containing proteins
5. different SH2 domains recognise P-Tyr in different sequence contexts

Question 43

amplification

Answer 43

= a single molecule of insulin can activate kinase that can phosphorylate many target molecules.

Question 44

Explain how Insulin stimulates glucose transport in fat and muscle cells

Answer 44

1. Glut4 (only expressed in these cell types) moves to the cell surface in response to insulin binding its receptor, this is triggered by activation of Akt.
2. Glut4 is packaged into secretory vesicles, waiting for the insulin signal
3. requires ATP
4. on addition of insulin, vesicles dock and fuse with plasma membrane and Glut4 is inserted/trafficked into plasma membrane.

Question 45

Akt

Answer 45

= a serine threonine kinase
- is a key enzyme activated by insulin
- leads to the amplification of all signalling pathways

Question 46

how insulin signals to glycogen synthesis enzymes

Answer 46

1. Insulin binds to its receptor, activating a cascade of phosphorylation events.
2. IRS proteins are phosphorylated, leading to the activation of PI3K and the production of PIP3.
3. Akt (PKB) is activated by PIP3, which inactivates GSK-3.
4. Dephosphorylation of Glycogen Synthase: This leads to the activation of glycogen synthase, promoting glycogen synthesis.
5. Enhanced Glycogen Storage: Increased glycogen synthesis helps lower blood glucose levels and store energy for future use.

Question 47

Discuss the utility of genetic mouse models to explain human physiology

Answer 47

1. genetically similar to humans
2. controlled experiment
3. behavioural studies
4. understanding development and ageing
5. disease modelling