Metabolism 2 Flashcards
What enzymes inside the cell phosphorylate glucose?
Hexokinases
What hexokinases are low in affinity for glucose? Where are they found?
Hexokinase-4 (glucokinase)
Liver + pancreatic β cells
What hexokinases are high in affinity for glucose? Where are they found?
Hexokinase
Brain, RBCs + muscle
The affinity of a hexokinase for glucose matches the affinity of the ___ in that tissue.
GLUTs
Briefly describe the anaerobic oxidation of glucose as in erythrocytes.
- Glucose converted to G6P via HK
- G6P converted to F6P via isomerase
- F6P converted to F-1,6-BP via PFK
- At this point 2 ATPs have been utilised
- Aldolase breaks F-1,6-BP down into dihydroxyacetone-P + Glyceraldehyde-3P (isomerase can interconvert them)
- Further investment of inorganic phosphate
- Series of reactions with various phosphorylated trioses to produce pyruvate
- Without O2, pyruvate is converted to lactic acid
How many ATPs does anaerobic glycolysis produce?
2
How is glycolysis linked to other biosynthetic pathways?
- G6P can be converted to glycogen/glycoconjugates
- F6P can be converted to glycoconjugates too or enter the PPP to produce nucleotides (DNA, RNA)
- Dihydroxyacetone-P can be converted to glycerol-3-P + be used to make triglycerides + phospholipids in lipogenesis
- Pyruvate can go into the mitochondria + become involved in oxidation or biosynthesis OR make AAs -> proteins
Where is most ATP formed? What process is used to do this?
Inside the mitochondrial inner membrane (location of ATP synthase)
Oxidative phosphorylation (involves ETC to create a proton gradient across membrane)
What do NADH and FADH2 do?
Carry electrons (reducing power) from catabolic reactions to the site of ATP synthesis
When oxygen is present and mitochondria are present, what is oxidised to produce ATP?
NADH + pyruvate from glycolysis
Why are mechanisms needed to transfer NADH into mitochondria?
It is not permeable through the mitochondrial inner membrane + it needs to get across so cells can harvest its reducing power to form ATP aerobically
How do cancer cells use glucose?
Anaerobically even when O2 is present (Warburg effect) which means they need to use glucose at a very high rate as this is an inefficient process
How many ATPs can be produced aerobically?
~36
What happens to pyruvate once it is imported into the mitochondria?
Oxidative decarboxylation via coenzyme A to produce acetyl-CoA, NADH + CO2 (by-product)
What are the products of fatty acid β-oxidation?
Acetyl-CoA
FADH2
NADH
What happens in fatty acid β-oxidation briefly?
- Lipid joined to coenzyme A
- Series of reactions where the β-carbon changes position + single/double bonds around it
- β-carbon gains a OH group by adding O2 in oxidation
- β-carbon then gains a =O
- Parts of the lipid will produce Acetyl-CoA whilst the rest will join directly to coenzyme A
Explain the mutual inhibition of glucose and fatty acid oxidation.
Glucose oxidation inhibits use of FA oxidation + vice versa because both processes produce Acetyl-CoA so one pathway is downregulated to avoid overproduction
What are amino acids required for the synthesis of?
Proteins (structural, catalytic, signalling)
Peptides (intra- + inter-cellular communication)
Sources of carbohydrates during fasting, trauma + sepsis
What needs to happen before amino acids can be used for glucose/lipid synthesis?
Deamination via a series of transamination reactions before urea formation
What is urea?
Main nitrogen-containing compound excreted through the kidneys (less toxic than ammonia so requires less dilution + fluid excretion) so urea is the main route of excretion of AA groups
What occurs during amino acid degradation?
AA R group is swapped with the R group of a ketoacid by transaminases
How is urea synthesized in the urea cycle?
- AA transamination with α-ketoglutarate via aminotransferase producing glutamate
- NH3 (amine group) removed from glutamate via glutamate dehydrogenase (NAD -> NADH)
- Also, glutamate converted to glutamine by a synthase
- NH3 (amine group) removed from glutamine by glutaminase
- Amine groups contribute to urea synthesis
- Aspartate also contributes to urea synthesis
What does alanine do when produced?
Cycles between muscle + liver
What is the main aim of catabolic reactions of glucose, fatty acids and amino acids?
Formation of Acetyl-CoA (but not all AAs can give rise to this)
What is the main aim of the Tricarboxylic Acid (TCA) Cycle?
Oxidation of Acetyl-CoA as a source of NADH + FADH2 (electron carriers) to produce CO2 in mitochondrial space
What are the important stages of the Tricarboxylic Acid (TCA) Cycle?
- Acetyl-CoA (2Cs) + oxaloacetate (4Cs) = citrate (6Cs) + CoA recycled via citrate synthase
- Series of reactions changing citrate back to oxaloacetate (4C)
- 2Cs put in every cycle at beginning via Acetyl-CoA released as 2CO2s
- 3NADH, FADH2 + GTP produced
What else is the Tricarboxylic Acid (TCA) Cycle involved in?
Many other metabolic processes may involve only parts of it:
- Anapleurotic roles in the liver
- Acetyl-CoA used to make ketone bodies e.g. in liver too
- All AAs feed in to the cycle which generates energy, gluconeogenesis
+ lipid metabolism
What is anapleurosis?
Replenishing of intermediates in the TCA cycle that have been extracted for biosynthesis
How is the urea cycle linked to the Tricarboxylic Acid (TCA) Cycle?
Oxaloacetate from TCA cycle converted to aspartate which goes into urea cycle
Fumarate from urea cycle joins the TCA cycle
What is the main aim of the electron transport chain (ETC)?
Conversion of energy harnessed from oxidation processes as NADH (from TCA cycle, FA β-oxidation + malate shuttle in glycolysis) + FADH2 (from TCA cycle, FA β-oxidation + G3P shuttle in glycolysis) into a usable form of high energy compound; ATP
What occurs in the electron transport chain (ETC)?
- NADH comes in first as FADH2 is not as useful
- Electrons transferred into a chain in the membrane which carries electrons from high to low energy state
- Electrons go through series of carriers + inner mitochondrial membrane spanning transporters (I, III + IV (also II but not important))
- The energy gained from this used to pump protons (H+) against their concentration gradient into intermembrane space across matrix
- 2 electrons join with O2 + 2Hs = H2O (by-product)
- ATP synthase allows H+ to flow back down concentration gradient producing energy (ATP) through ADP phosphorylation
- ATP transported out of mitochondria, across inner membrane + into cytoplasm via a ATP-ADP carrier
How is the Electron Transport Chain (ETC) coupled to ATP synthesis?
For each 2 electrons transported across complex I + III, 4 proteins ejected across inner mitochondrial membrane by each complex
ATP synthase requires 3 proteins flowing down their concentration gradient to synthesize 1 ATP - 4th proton symported with each ATP across the inner membrane in exchange for 1 ADP
What is the Cori cycle briefly?
When lactate is produced from anaerobic glycolysis goes back to the liver + is converted back to glucose so glucose gets another change to gain more energy aerobically
What other intermediates can be produced by the Electron Transport Chain (ETC)?
ROS which can react with anything e.g. DNA causing cell damage + ageing
How can proton influx be uncoupled from ATP synthesis? What is the consequence of this?
UCP1
Dissipation of the proton (H+) gradients results in release of heat resulting in non-shivering thermogenesis in brown adipose tissue - useful as part of homeostasis if your cold as fat tissue takes the energy + uses it differently to create heat
