L1 - Intro to metabolism and metabolic control

Question 1

Metabolism definition

Answer 1

Obtaining chemical energy by capturing solar energy or degrading energy-rich nutrients from the environment

Polymerize precursor molecules into macromolecules

Question 2

Catabolic pathways: what do they do, what do they produce, and what forms do they take?

Answer 2

Catabolic pathways break down energy containing macromolecules to produce chemical energy in the form of ATP, NADH, NADPH, and FADH2.

Degradation, releases energy

Question 3

Anabolic pathways: what do they do, what do they produce, and what forms does it take?

Answer 3

Anabolic pathways use these energy carriers to convert small precursor molecules into cellular macromolecules (proteins, etc)

Biosynthesis, requires energy

Question 4

Where does glycolysis occur?

Answer 4

Cytosol

Question 5

Citric acid cycle

Answer 5

Mitochondria

Question 6

Gluconeogenesis

Answer 6

Liver tissue - cytosol mainly (?)

Question 7

Fatty acid synthesis

Answer 7

Mitochondria

Question 8

β-oxidation of fatty acids

Answer 8

Mitochondria

Question 9

Triacylglycerol synthesis

Answer 9

ER

Question 10

Phospholipid synthesis

Answer 10

ER

Question 11

Amino acid synthesis

Answer 11

Cytoplasm/mitochondria

Occurs using intermediates gathered from the citric acid cycle

Question 12

Amino acid degradation

Answer 12

Liver mainly (17/20) but also in:
* Kidney
* Skeletal muscle
* Muscle
* Adipose tissue
* Small intestines

Valine, leucine, and isoleucine occur in the tissues above as they are branched chain amino acids - cannot be transaminated in the liver

Question 13

Oxidative phosphorylation/ATP synthesis

Answer 13

Glycolysis - cytosol

Aerobic respiration - inner mitochondria membrane

Question 14

Glycogen synthesis and breakdown: in what tissues do they occur?

Answer 14

Synthesis - liver/muscle mainly
Breakdown - liver mainly

Question 15

Protein synthesis

Answer 15

Extracellular - ribosomes on the ER
Intracellular - cellular 70s (?) ribosomes

Question 16

Lipoprotein synthesis

Answer 16

ER

Question 17

Which pathways involve several subcellular compartments?

Answer 17

• Urea synthesis - mitochondria/cytosol
• Release of glucose from glycogen - mitochondria/cytosol
• Cholesterol synthesis - cytosol/endoplasmic reticulum
• Long-chain fatty acids - cytoplasm (FAS2 type I) and in mitochondria (FAS type II)

Question 18

Maintaining overall metabolical balanced

Answer 18

Requires equal production and consumption of intermediates

v₁ v₂
A->S->P

A -
S -
P -
v - metabolic rate/flux

When v₁ and v₂ are equal, [S] is equal - homeostasis

Question 19

Reaction flux: what is it and what affects it?

Answer 19

Enzyme-catalyzed reaction rate

• Number/concentration of enzyme molecules
• -Catalytic activity of each enzyme molecule

Both can be modulated to increase or decrease the total activity of an enzyme

Question 20

The 10 key factors that affect enzyme activity

Answer 20

1–5 - change the number of molecules of the enzyme:
* Extracellular signals
* Transcription of specific genes
* mRNA degradation
* mRNA translation of ribosome
* Protein degradation

6 – movement of the enzyme between subcellar compartments

7–10 change the catalytic activity of the enzyme:
* Enzyme-substrate binding
* Allosteric activation/inhibition
* (de)Phosphorylation
* Regulatory protein binding

Question 21

Extracellular signals: what is an example and what can they do?

Answer 21

Hormones - carried in the bloodstream from endocrine gland (e.g. pancreas) to target cells or organs (e.g. liver)

Bring about changes in target cell, change in transcription of genes encoding metabolic enzymes or may cause altered activity of existing enzyme

Question 22

Transcription of specific genes

Answer 22

May be influenced by intra or extracellular signals

Question 23

mRNA degradation

Answer 23

mRNA degradation - should result in less production

Question 24

mRNA translation of ribosome

Answer 24

mRNA translation - should result in increased production

Question 25

Protein degradation

Answer 25

Once synthesised, protein molecules have finite lifetime, the rate of degradation differs from one enzyme to another Liver enzymes: <1 hour - > 1 week Degradation can be regulated to alter enzyme concentration Example: HMG-CoA reductase (cholesterol biosynthesis)

Question 26

Movement of the enzyme between subcellar compartments

Answer 26

Movement of metabolites between compartments can also be a point of regulation Example - Glucokinase regulatory protein sequesters hexokinase IV (glucokinase) in the nucleus (ePBL)

Question 27

Enzyme-substrate binding: how does substrate concentration affect the rate, what is kₘ, when does kₘ reaction rate depend on the substrate concentration, and what is the typical enzyme kₘ?

Answer 27

The rate is more sensitive to increase due to substrate concentration at low concentrations - the frequency of substrate meeting the enzyme is limiting The rate becomes insensitive at high substrate concentrations - the enzyme is nearly saturated with substrate kₘ - the concentration of substrate that allows the enzyme to achieve half vₘₐₓ * When [substrate] < Km * If Km is greater than physiological [substrate], changes in [substrate] will alter reaction rate Many enzymes have Km near or greater than the physiological [substrate], meaning that changes in [substrate] will cause changes in reaction rate

Question 28

Allosteric activation/inhibition: what are the molecules that cause allosteric effects, do they activate or inhibit, and how do they do their function?

Answer 28

Allosteric effectors or modulators are generally small molecules - often metabolites, intermediates, or end-products of a pathway Allosteric effectors can be activators or inhibitors Bind non-covalently to a specific regulatory site that is different to the active site

Question 29

(de)phosphorylation: what are they caused by, what specific components of substances are affected, and what is their effect?

Answer 29

* Phosphorylation is catalysed by protein kinases * Dephosphorylation is catalyzed by protein phosphatases (can be spontaneous) Specific amino acids are phosphorylated The phosphate group alters properties e.g. structure leading to change in activity

Question 30

Regulatory protein binding: what is it and what is the example?

Answer 30

The binding of regulatory protein subunits can affect the specificity E.g. phosphoprotein phosphatase 2A (PP2A) * Recognizes several substrate proteins * Specificity is determined by regulatory subunit *Creates unique substrate binding site - conferring specificity

Question 31

Compartmentalisation: why is it useful?

Answer 31

Anabolic/catabolic pathways of substances can be separated and regulated without interfering with one another

Question 32

How much of the genome is regulatory?

Answer 32

Thought to be up to 10%! This is because the importance of keeping homeostasis