L1 - Intro to metabolism and metabolic control Flashcards
Metabolism definition
Obtaining chemical energy by capturing solar energy or degrading energy-rich nutrients from the environment
Polymerize precursor molecules into macromolecules
Catabolic pathways: what do they do, what do they produce, and what forms do they take?
Catabolic pathways break down energy containing macromolecules to produce chemical energy in the form of ATP, NADH, NADPH, and FADH2.
Degradation, releases energy
Anabolic pathways: what do they do, what do they produce, and what forms does it take?
Anabolic pathways use these energy carriers to convert small precursor molecules into cellular macromolecules (proteins, etc)
Biosynthesis, requires energy
Where does glycolysis occur?
Cytosol
Citric acid cycle
Mitochondria
Gluconeogenesis
Liver tissue - cytosol mainly (?)
Fatty acid synthesis
Mitochondria
β-oxidation of fatty acids
Mitochondria
Triacylglycerol synthesis
ER
Phospholipid synthesis
ER
Amino acid synthesis
Cytoplasm/mitochondria
Occurs using intermediates gathered from the citric acid cycle
Amino acid degradation
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
Oxidative phosphorylation/ATP synthesis
Glycolysis - cytosol
Aerobic respiration - inner mitochondria membrane
Glycogen synthesis and breakdown: in what tissues do they occur?
Synthesis - liver/muscle mainly
Breakdown - liver mainly
Protein synthesis
Extracellular - ribosomes on the ER
Intracellular - cellular 70s (?) ribosomes
Lipoprotein synthesis
ER
Which pathways involve several subcellular compartments?
- 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)
Maintaining overall metabolical balanced
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
Reaction flux: what is it and what affects it?
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
The 10 key factors that affect enzyme activity
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
Extracellular signals: what is an example and what can they do?
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
Transcription of specific genes
May be influenced by intra or extracellular signals
mRNA degradation
mRNA degradation - should result in less production
mRNA translation of ribosome
mRNA translation - should result in increased production
Protein degradation
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)
Movement of the enzyme between subcellar compartments
Movement of metabolites between compartments can also be a point of regulation
Example - Glucokinase regulatory protein sequesters hexokinase IV (glucokinase) in the nucleus (ePBL)
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?
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
Allosteric activation/inhibition: what are the molecules that cause allosteric effects, do they activate or inhibit, and how do they do their function?
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
(de)phosphorylation: what are they caused by, what specific components of substances are affected, and what is their effect?
- 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
Regulatory protein binding: what is it and what is the example?
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
Compartmentalisation: why is it useful?
Anabolic/catabolic pathways of substances can be separated and regulated without interfering with one another
How much of the genome is regulatory?
Thought to be up to 10%!
This is because the importance of keeping homeostasis
