Cellular Metabolism Flashcards
How much free energy is required to hydrolyse ATP?
-31 Kjmol^-1
How much free energy is required for Glucose Combustion?
2872 Kjmol^-1
How much free energy is required for Glucose Metabolism?
-1178 Kjmol^-1
What is an oxidation-reduction reaction?
Electron transfer
What is ligation requiring ATP cleavage?
Formation of covalent bonds ie carbon carbon
What is isomerisation?
Rearrangement of atoms to form isomers
What is group transfer?
Transfer of functional group from one molecule to another
What is a hydrolytic reaction?
Cleavage of bonds by The addition of water
What is addition or removal of functional groups?
Addition to break a double bond or removal to form one
What reaction does hexokinase catalyse?
Glucose to Glucose-6-phosphate, produces H+ and ADP
How is Glucose-6-phosphate made? What is the significance of this step?
Glucose > Glucose-6-phosphate by hexokinase
Irreversible reaction, traps glucose inside cell by means of negative charge
What reaction does phosphoglucose isomerase catalyse?
Glucose-6-phosphate > Fructose-6-phosphate
How is Fructose-6-phosphate formed?
Glucose-6-phosphate > Fructose-6-phosphate via Phosphoglucose isomerase
How is Fructose-1,6-bisphosphate formed?
Fructose-6-phosphate > Fructose-1,6-bisphosphate via phosphofructo kinase
ADP is produced
What reaction does phosphofructo kinase catalyse?
Fructose-6-phosphate > Fructose-1,6-bisphosphate
What reaction does aldolase catalyse?
Fructose-1,6-bisphosphate into both Dihydroxy acetone phosphate and glyceraldehyde-3-phosphate
What is the role of TPI (triode phosphate isomerase)?
Dihydroxy acetone phosphate > glyceraldehyde-3-phosphate
What is the only glycolytic enzomyopathy that is fatal?
Deficiency in TPI, most die in the first 6 years
What is the role of G-3-P dehydrogenase?
Converts glyceraldehyde-3-phosphate into 1,3-biphosphoglycerate
Generates NADH
What is the role of Phosphoglycerate kinase?
1,3-biphosphoglycerate > 3-phosphopglycerate
Generates ATP
What is the role of Phosphoglycerate mutase
3-phosphopglycerate > 2-phosphpglycerate
What is the role of enolase?
2-phosphpglycerate > phosphoenal pyruvate
What is the role of pyruvate kinase?
Phosphoenal pyruvate > pyruvate
Generates ATP
What are the three products Pyruvate can form?
Ethanol
Lactate
Acetyl-CoA
How is ethanol made?
Pyruvate – (pyruvate decarboxylase)–> acetaldehyde – (alcohol dehydrogenase) –> ethanol
step 1 - H+ > CO2
step 2 - NADH + H+ > NAD+
How is lactate made?
Pyruvate – (Lactate dehydrogenase)–> lactate
NADH + H+ > NAD+
How is Acetyl-CoA made?
Pyruvate + HS-CoA – (pyruvate dehydrogenase complex)–> Acetyl-CoA + CO2
NADH is generated
Commits the acetyl CoA into the TCA cycle
What is the net result of glycolysis?
4 ATP and 2 NADH
What is the net result of glycolysis?
4 ATP and 2 NADH
Which two reactions generate NAD+ and why is this needed?
Alcohol fermentation and generation of lactate
Allows glycolysis to continue in time of oxygen depletion
- How much free energy is required to break down creatine phosphate?
-43 Kj/mol
What is thiamine pyrophosphate a cofactor of?
The PDH (Pyruvate Dehydrogenase) complex - used to convert pyruvate to acetyl co A committing it to kerbs
What condition does a deficiency in thiamine result in and what are the symptoms of this condition?
Beri-Beri
Damage to peripheral nervous system, weakness of musculature and decreased cardiac outpu
What is the net result of the Krebs cycle?
3 NADH
2 CO2
1 FADH2
1 GTP
What conditions does the Krebs cycle require?
Aerobic
What are the steps of the krebs cycle?
Pyruvate > citrate > isocitrate > a-ketoglutarate > Succinyl CoA > succinate > fumerate > Malate > oxaloacetate > pyruvate
(Can i kill someone soon for my own pleasure?)
What 7 molecules do all 20 amino acids degrade to?
- pyruvate
- Acetyle CoA
- a-ketoglutarate
- succinyl CoA
- fumarate
- oxaloacetate
What is a glucogenic amino acid ?
An amino acid that when degraded its molecule can be converted into glucose
Which two molecules do ketogenic amino acids degrade into?
Acetyl CoA and Acetoacetyl CoA
Which 5 molecules do glucogenic amino acids degrade to?
Pyruvate a-ketoglutarate Succinyl CoA Fumarate Oxaloacetate
Explain Transamination with an example
Allows production of non-essential amino acids by transferring amine group to keto acids
Alanine + alpha-ketoglutarate → pyruvate + glutamate
(Amine and oxygen switched to form glutamate and pyruvate)
Amino Acid —(NH4+)→ Keto acid Group Transfer
Pyruvate then enters Kreb’s cycle and glutamate is reconverted into alpha-ketoglutarate by glutamate dehydrogenase to form the amino group
What is the purpose of the Glycerol Phosphate Shuttle
To carry electrons from NADH from the cytosol into the matrix of mitochondria in skeletal muscle and the brain
Where in the body is the Glycerol-Phosphate Shuttle, used?
Skeletal Muscle
Brain
Explain how the Glycerol-Phosphate Shuttle works
- Cytosolic glycerol-3-phosphate dehydrogenase transfers electrons from NADH to DHAP
dihydroxyacetone phosphate > Glycerol-3-Phosphate - membrane bound form of same enzyme transfers electrons to FAD to get passed to Coenzyme Q (part of the electron transport chain), also reforming DHAP
Where in the body is the Malate-Aspartate Shuttle used?
Liver
Kidney
Heart
How does the malate aspartate shuttle work
Aspartate — (aspartate transaminase converts a-ketoglutarate into glutamate)—> oxaloacetate —(malate dehydrogenase converts NADH to NAD+)—> malate
Malate is transported into the mitochondria by the malate-a-ketoglutarate antiporter
malate –(malate dehydrogenase converts NAD+ to NADH)—> oxaloacetate —(aspartate transaminase converts glutamate into a-ketoglutarate)—> Aspartate
Glutamate-aspartate antiporter takes aspartate into the cytosol
What is the Warburg Effect?
Mutations in genes of Fumerase, Succinate dehydrogenase, Isocitrate Dehydrogenase, decreases Kreb’s Cycle activity which enhances anaerobic glycolysis
Preferential generation of lactate from glucose even in increased O2 availability
this can turn cells into malignant cancerous cells
In which three areas can amino acids feed in to be metabolised?
Pyruvate, acetyl CoA or straight into the ETC
What are the three basic steps for beta oxidation?
- make acyl CoA (outer mitochondrial membrane)
- transport Acyl CoA into the matrix via the carnitine shuttle
- beta oxidation itself
Which transporter allows the carnitine shuttle to work?
Translocase
What enzyme turns carnitine into acyl carnitine and which side does this occur?
Acyl transferase I
(acyl CoA > CoA)
Cytoplasmic side
What enzyme turns acyl carnitine into carnitine and which side does this occur?
acyl transferase II
(CoA > acyl CoA)
matrix side
What is used and generated in each beta oxidation cycle?
used - FAD, NAD+ and H2O
made - FADH2, NADH and acetyl CoA
What is primary carnitine deficiency?
Autosomal recessive disorder
symptoms appear during infancy or early childhood and include encephalopathies, (cardiomyopathies, muscle weakness and hypoglycaemia)
Mutations in a gene SLC22A5 which encodes a carnitine transporter results in reduced ability of cells to take up carnitine needed for beta oxidation
Name the four reactions in beta oxidation.
Oxidation
hydration
Oxidation
thialysis
What are the four steps of fatty acid synthesis and which enzyme is used for it?
CoA carboxylase Condensation ketoreductase Reduction dehydratase Dehydration enolreductase Reduction crazy calm Kangaroos run down ‘da’hills every ramadan
What molecules are first condensed in fatty acid synthesis? What product forms at the end?
Malonyl-CoA3 and activated acetyl group
forms activated acyl group linked to acyl carrier protein ( two carbon atoms longer)
What are the three distinctions between fatty acid synthesis and degradation?
carriers- ACP v CoA
reducing power: NADPH v FAD/NAD+
location: Cytoplasm v mitochondrial matrix
When does acetyl CoA generated by B oxidation enter the TCA cycle?
What happens if it doesn’t occur?
When b oxidation. and carbohydrate metabolism are. balanced
When fat breakdown predominates - ie during fasting- acetyl CoA forms acetoacetate, D-3-hydroxybutarate and acetone (ketone bodies)
Describe the process of lipogenesis
FA are formed sequentially by decarboxylative condensation reactions, involving the molecules acetyl-CoA and malonyl CoA
Following a round of elongation, the FA undergoes reduction and dehydration by ketoreductase, dehydratase and enol reductase
The growing fatty acyl group is linked to an acyl carrier protein
What enzyme catalyses the initial step in each cycle of beta oxidation within the mitochondrial matrix?
Acyl-CoA-dehydrogenase
What is MCADD
medium chain acyl-coenzyme A dehydrogenase deficiency
autosomal recessive condition
patients should not go longer than 10-12 hours without food and adhere to a high carb diet
Explain the process of ketone body formation?
Acetyl Co-A → acetoacetyl CoA → 3-hydroxy-3-glutaryl CoA → acetoacetate → D-3-hydroxybutyrate and acetone
