OC2 - main concepts of human metabolism

Question 1

what is a metabolic pathway?

Answer 1

metabolic pathways are a series of interconnected biochemical reactions that convert a substrate molecule or molecules step-by-step through a series of metabolic intermediates, eventually yielding a final product or products
a specific enzyme catalyses each step of a metabolic pathway.

Question 2

what are the type of metabolic pathway?

Answer 2

anabolic
catabolic
amphibolic
linear
cyclic branched
cpiral
multi-enzyme complexes

Question 3

what is an anabolic metabolic pathway?

Answer 3

builds up complex molecules from simple molecules
requires energy - ATP > ADP + Pi
endergonic

Question 4

what is a catabolic metabolic pathway?

Answer 4

breaks down complex molecules into simple molecules
release energy (for anabolism)
provides the energy for ADP + Pi > ATP
exergonic

Question 5

what is an amphibolic metabolic pathway?

Answer 5

comprised of both anabolic and metabolic pathways

Question 6

what is a linear metabolic pathway?

Answer 6

series of independent enzymes
product is the substrate for the next reaction
e.g. glycolysis

Question 7

what is a cyclic metabolic pathway?

Answer 7

intermediates are regenerated every turn
e.g. citric acid cycle

Question 8

what is a spiral metabolic pathway?

Answer 8

same set of enzymes are used repeatedly
polymerisation reactions
e.g. fatty acid synthesis

Question 9

what are the key junctions in human metabolism?

Answer 9

glucose-6-phosphate
pyruvate
acetyl CoA

Question 10

how is metabolism regulated?

Answer 10

reciprocal regulation
compartmentation
multi-enzyme complexes

Question 11

what is reciprocal regulation?

Answer 11

allosteric inhibition (non-competitive) occurs
when one process is highly active the other one is inhibited

Question 12

what is the advantage of reciprocal regulation?

Answer 12

prevents concurrent activity in two closely parallel pathways, as these would waste ATP is allowed to run freely
used because if two processes occur simultaneously there would be a net amount of ATP molecules that are made and then used up so none would be produced

Question 13

what is an example of reciprocal regulation?

Answer 13

glycolysis and gluconeogenesis
production of and breakdown of glucose occurring at the same time is counterintuitive

Question 14

what is compartmentation?

Answer 14

controls metabolism by segregating opposing reactions - enzyme is in one compartment and the substrate is in another

Question 15

what is the advantage of compartmentation?

Answer 15

prevents the reaction saving energy and resources

Question 16

what is an example of compartmentation?

Answer 16

gluconeogenesis bypass I
oxaloacetate is in the mitochondria where as gluconeogenesis occurs in the cytoplasm

Question 17

what is a multi-enzyme complex?

Answer 17

enzymes of a particular pathway are frequently organised spatially so that metabolic channeling can occur

Question 18

what is metabolic channeling?

Answer 18

the passing of intermediates from enzyme to enzyme

Question 19

what is the advantages of a multi-enzyme complex?

Answer 19

increased efficiency
concentration of reactions in one location
preventing unwanted side reactions
protection of intermediates
channeling substrates from one enzyme to the next

Question 20

what is an example of a multi-enzyme complex?

Answer 20

electron transport chain

Question 21

what is the role of ATP?

Answer 21

ATP is the principle molecule for storing and transferring energy in cells
ATP is kinetically stable and it degrades/ hydrolyses very slowly

Question 22

what is the structure of ATP?

Answer 22

adenosine triphosphate
adenine base + ribose sugar + 3x phosphate

Question 23

what are phosphoanhydride bond?

Answer 23

between the phosphate groups
high energy bonds
broken by hydrolysis
ATP > ADP > AMP

Question 24

what are ATP and ADP?

Answer 24

nucleotides
coenzymes

Question 25

what is the role of ATP as an energy currency?

Answer 25

ATP shuttles energy between catabolic and anabolic processes in the cell
catabolic processes involve ATP synthesis
energy provided from catabolism is given to anabolism
energy from catabolism converts ADP + Pi > ATP, which is the formation of a high energy phosphoanhydride bond
energy is provided to anabolism by ATP hydrolysis

Question 26

what are endergonic reactions?

Answer 26

products have greater free energy than reactants
ΔG is positive
require input of energy
anabolic reactions

Question 27

what are exergonic reactions?

Answer 27

products have lower free energy than reactants
ΔG is negative
release energy and can occur spontaneously
catabolic reactions

Question 28

what is substrate level phosphorylation?

Answer 28

a phosphate group is transferred directly from a substrate to ADP
occurs in the cytoplasm and the mitochondrial matrix
direct phosphorylation
e.g. creatine phosphate

Question 29

what is oxidative phosphorylation?

Answer 29

uses the energy release from the electron transport chain to generate ATP
occurs in the inner membrane of the mitochondria
indirect phosphorylation
e.g. electron transport chain

Question 30

what is the creatine phosphate substrate level phosphorylation example?

Answer 30

creatine phosphate is a high energy phosphate supply in the brain and skeletal muscle
creatine phosphate + ADP > creatine + ATP
enzyme = creatine kinase

Question 31

what is the process of binding of water soluble hormones?

Answer 31

water soluble hormones cannot diffuse through the cell membrane so bind to a surface cell membrane receptor
1. water-soluble hormones are lipid insoluble. they bind to membrane receptors
2. the binding activates a G-protein
3. the activated G-protein activates adenylyl cyclase
4. adenylyl cyclase catalyses the conversion of ATP to cAMP - the second messenger
5. cAMP activates protein kinase A
6. protein kinase a phosphorylates proteins in the cytoplasm activating them and allowing them to alter cell activity.

Question 32

what is the process of binding lipid soluble hormones?

Answer 32

directly initiates the production of proteins within a target cell
1. lipid-soluble hormone diffuse through the cells plasma membrane
2. hormone binds with receptor in the cytoplasm, forming a receptor-hormone complex
3. receptor-hormone complex enters the nucleus and triggers gene transcription by binding to the target gene on the DNA
4. transcribed mRNA is translated into proteins that alter cell activity

Question 33

what is insulin?

Answer 33

produced in the beta cells in the islets of langerhans in the pancreas
insulin is secreted in response to elevated blood glucose levels
main effects of insulin increase are on muscle, fat and liver cells
increased insulin increases glycogenesis

Question 34

what is the insulin signal transduction pathway?

Answer 34

1. insulin binds to the tyrosine kinase insulin receptor which triggers phosphorylation of the tyrosine receptors
2. phosphorylation activates tyrosine kinase which triggers a signal transduction pathway activating other protein kinases - specifically protein kinase B (PKB)
   2.1 PKB triggers the translocation of glucose transporter (GLUt-4) containing vesicles to the cell membrane to facilitate the diffusion of glucose into the cell
   2.2 PKB phosphorylates glycogen synthase kinase which inhibits the enzyme so glycogen is synthesised.
   PKB starts the process of glycogenesis
   once an insulin molecule has effected its action it may be released back into the extracellular environment, or, be degraded by endocytosis using insulin degrading enzyme in the liver

Question 35

what is glucose stimulated insulin secretion?

Answer 35

1. glucose is transported into the beta cell by facilitated diffusion through a glucose transporter
2. due to the TCA cycle the intracellular ATP:ADP ratio is increased
3. this closes the ATP-sensitive potassium channels leading to membrane depolarisation
4. due to depolarisation, voltage-gated calcium ion channels open and calcium ions move into the cell by facilitated diffusion
5. increase in intracellular calcium triggers exocytosis of insulin containing secretory granules
6. insulin is secreted into the blood

Question 36

what is the glucagon GPCR process?

Answer 36

1. glucagon binds to the GPCR causing a conformational change
2. G-protien is activated by GDP being replaced with GTP
3. the ⍺- subunit dissociates and activates adenylyl cyclase which catalyses the formation of cyclic AMP from ATP
4. cAMP activates protein kinase A which exists in a R2C2 complex and binding of 4 cAMP molecules to the two regulatory subunits activating a phosphorylation cascade (phosphorylase kinase - PPK)
5. phosphorylase a (PYGa) enzyme releases glucose-1-phosphate from glycogen polymers
6. this process is reversible as PKA regulates the activity of glycogen synthase (GYSa > GYSb) which in turn regulates conversion of glucose to glycogen