Cell Metabolism Flashcards
What does glycolysis produce?
2 x Pyruvate
2 x NADH
2 x Net ATP
What reaction is irreversible and commits the cell to glycolysis?
The conversion of glucose to glucose - 6 - phosphate
What is the complete reaction steps of glycolysis?
Glucose
Glucose - 6 - Phosphate
Fructose - 6 - Phosphate
Fructose - 1,6 - Bisphosphate –> dihydroxyacetone phosphate and
Glyceraldehyde - 3 - Phosphate
1,3 - Bisphosphoglycerate
3 - Phosphoglycerate
2 - Phosphoglycerate
Phosphenolpyruvate
Pyruvate
Which step of glycolysis does phosphofructokinase control?
The conversion of fructose - 6 - phosphate into fructose - 1,6 - bisphosphate
What does TPI stand for?
Triose phosphate isomerase
What does hexokinase catalyse?
The conversion of glucose into glucose - 6 - phosphate
What is the only glycolytic enzymopathy which is fatal?
Deficiency in TPI
Which reactions produce ATP?
The conversion of 1,3-Bisphosphoglycerate into 3-phosphglycerate and phosphenolpyruvate into pyruvate
What do kinases do?
Transfer phosphate groups to molecules
Which step in glycolysis needs NAD+?
Glyceraldehyde - 3 - phosphate into 1,3 - bisphosphoglycerate
Which steps of glycolysis require ATP?
Glucose -> glucose - 6 - phosphate
Fructose - 6 - phosphate -> Fructose - 1,6 - bisphosphate
Does glycolysis need oxygen to occur?
No - it is anaerobic
Where does glycolysis occur?
In the cytoplasm
Why are high energy phosphate groups added to some of the substrates involved in glycolysis?
Adding the phosphate groups makes them easier to split as they are more reactive
What are the three fates of pyruvate?
- Lactate generation
- Acetyl CoA Production
- Alcohol fermentation
What enzyme is needed to generate Acetyl CoA from pyruvate?
Pyruvate dehydrogenase complex
What does pyruvate dehydrogenase needed as a cofactor?
Thiamine
What does a deficiency in thiamine result in?
Beri - Beri
This is a condition which leads to muscle weakness
How is pyruvate converted into lactate?
Using lactate dehydrogenase complex
What does the fermentation of alcohol and lactate production both regenerate?
NAD+ - this is needed for glycolysis to continue occurring
What happens to the Acetyl CoA that is produced?
It enters into the Krebs Cycle
What are the stages of the Krebs Cycle?
Acetyl CoA combines with oxaloacetate to make Citrate
Then Alpha - keto glutarate
Succinyl CoA
Succinate
Fumerate
Malate
What does the Krebs cycle produce?
2 x CO2
1 x GTP
3 x NADH
1 x FADH
What reaction in the Krebs cycle produces FADH?
The conversion of succinate to fumerate
Where does the krebs cycle occur?
The mitochondrial matrix
What is a transamination reaction?
the process of removing an amine group from one amino acid and transferring it to a ketoacid, producing another ketoacid and amino acid
What are the seven things which can be produced from transamination reactions?
Pyruvate
Succinyl CoA
Acetoacetyl CoA
Acetyl CoA
Oxaloacetate
Alpha Keto Glutarate
Fumerate
Explain Alcoholic Fermentation of Pyruvate
Pyruvate is converted into Acetaldehyde using pyruvate decarboxylase. Then using alcohol dehydrogenase is used to convert the acetaldehyde into ethanol
Why is it essential that NAD+ is regenerated?
Needed for dehydrogenation of glyceraldehyde-3-phosphate to produce ATP
Allows glycolysis to occur anaerobically
What is the Warburg effect?
Mutations in genes of Fumerase, Succinate, Isocitrate Dehydrogenase, decreases Kreb’s Cycle activity which enhances anaerobic glycolysis
What are glucogenic amino acids?
Ones whose carbon skeletons are used to make glucose
What are ketogenic amino acids?
Amino acids which when they are broken down, form ketone body precursors like Acetyl CoA
During fasting, which type of metabolism dominates?
fat metabolism, resulting in the production of ketone bodies
What happens when the levels of Acetyl CoA is not equal to Oxaloacetate?
The excess Acetyl CoA is used to make ketone bodies
What are the names of the three ketone bodies?
Acetone, Acetoacetate and 3 - Beta - Hydroxy Butyrate
Why can ketone bodies be utilised by the brain but fatty acids cannot?
Fatty acids can’t cross the blood brain barrier
What is the purpose of the Glycerol Phosphate Shuttle
To carry electrons from NADH across the matrix - this is because the mitochondrial matrix is impermeable to NADH
Where in the body is the Glycerol-Phosphate Shuttle used?
brain and skeletal muscle
Explain how the Glycerol-Phosphate Shuttle works
Cytosolic glycerol-3-phosphate dehydrogenase transfers electrons from NADH to DHAP → Glycerol-3-Phosphate
The G-3-P is then converted back into DHAP, and FAD is reduced to form FADH2
The FADH2 electrons are then passed onto molecule Q which is in the electron transport chain
Where in the body is the Malate-Aspartate Shuttle used?
Liver, kidney and the heart
Outline the processes in the Malate-Aspartate Shuttle
Malate enters into the matrix NADH is generated from NAD+ which then regenerates oxaloacetate
What is a ligation requiring ATP cleavage reaction?
Formation of covalent bonds eg carbon-carbon bonds
What is an isomerisation reaction?
The rearrangement of atoms to form isomers
What is a group transfer reaction?
The transfer of a function group from one molecule to another
What is a hydrolytic reaction?
The cleavage of bonds by the addition of water
What are the two main concepts of glycolysis?
The formation of a high energy compound, and the splitting of this compound
Why is the generation of NADH useful?
NADH is generated here which can be later used to generate yet more ATP within the mitochondria in a process known as oxidative phosphorylation
Why is creatine phosphate used as a buffer?
In muscle, the amount of ATP needed during exercise is only enough to sustain contraction for around one second.
Describe how creatine phosphate is used to generate ATP?
Creatine phosphate -> creatine + ATP
How is creatine used by athletes?
As a dietary supplement
How is Acetyl CoA able to donate the acetate group (2C) to other molecules?
The thioester linkage which it contains is a high energy linkage so is readily hydrolysed
What are the symptoms of Beri Beri?
damage to the peripheral nervous system, weakness of the musculature and decreased cardiac output.
What enzyme is used in the transamination reaction of alanine?
Alanine (C3) undergoes transamination by the action of the enzyme alanine aminotransferase.
What does the transamination of alanine produce?
Pyruvate and glutamate
What type of reaction is occuring in the Malate-Aspartate Shuttle?
Transamination reaction
Mutations in which TCA genes have been shown to decrease TCA activity and enhance aerobic glycolysis?
Isocitrate dehydrogenase
Succinate dehydrogenase
Fumerase
How many ATP does the oxidation of one Acetyl CoA produce?
12
How many ATP molecules are formed by the reoxidation of each NADH?
3
How many ATP molecules are formed by the reoxidation of each FADH?
2
What is the name of the process of fatty acid metabolism?
Beta oxidation
where does beta oxidation occur?
In the mitochondria
How are fatty acids converted into an Acyl CoA Species?
Using Acyl CoA synthetase
Where does the generation of Acyl CoA occur?
In the outer mitochondrial membrane
What is the name of the shuttle used to transport Acyl CoA species into the miatrix?
Carnitine shuttle
Describe how the carnitine shuttle works?
Acyl CoA is coupled to the molecule carnitine to form acyl carnitine - this is done using an enzyme carnitine acyltransferase 1
The acyl carnitine is then shuttle across the membrane via translocase
The acyl Carnitine is then converted back into carnitine and Acyl CoA
What is used as a supplement when you have primary carnitine deficiency?
Carnitor / levocarnitine
What type of deficiency is primary carnitine deficiency?
Autosomal recessive disorder
What are some symptoms of primary carnitine deficiency?
encephalopathies, cardiomyopathies, muscle weakness; and hypoglycaemia
Describe the mutations involved in primary carnitine deficiency?
Mutations in a gene known as SLC22A5 which encodes a carnitine transporter result in reduced ability of cells to take up carnitine, needed for the β-oxidation of fatty acids.
What are the four reactions in Beta-oxidation?
oxidation, hydration, oxidation and thiolysis
What does one cycle of beta oxidation result in?
The produce of Acetyl CoA and an Acyl CoA species which is 2 carbons shorter than the original
Write the overall equation for the Beta-Oxidation of palmitoyl CoA?
palmitoyl CoA + 7 FAD + 7 NAD+ + 7 H2O + 7 CoA —-> 8 acetyl CoA + 7 FADH2 + 7 NADH
What happens to the acetyl CoA generated through beta-oxidation?
Enters the TCA cycle only if Beta oxidation and carbohydrate metabolism are balanced, as oxaloacetate is needed for entry
What does Acetyl CoA form during fasting?
D-3-hydroxybutyrate, Acetone and Acetoacetate
What is fatty acid biosynthesis known as?
Lipogenesis
What are the two enzymes involved in fatty acid biosynthesis?
Acetyl CoA Carboxylase and fatty acid synthesis
What are the three enzymes which are involved in lipogenesis?
Ketoreductase, dehydratase and enol reductase
During lipogenesis, what is the growing fatty acid group linked to?
An Acyl carrier protein
What are the differences in carriers between synthesis and degradation of fatty acids?
Carriers - synthesis uses Acyl Carrier Protein while degradation uses CoA
What are the differences in reducing powers between synthesis and degradation of fatty acids?
Synthesis uses NADPH but degradation uses FAD/NAD+
What are the differences in location between synthesis and degradation of fatty acids?
Synthesis occurs in the cytoplasm, but fatty acids degradation occurs in the mitochondrial matrix
What is the overall reaction of lipogenesis, to form Palmitate?
Acetyl CoA (C2) + 7 Malonyl CoA (C3) + 14 NADPH +14 H+
—-> Palmitate (C16) + 7 CO2+ 6 H2O + 8 CoA-SH + 14 NADP+
What does the desaturation of fatty acids required?
the action of fatty acyl-CoA desaturases
What is the enzyme that creates oleic acid and palmitoleic acid from stearate and palmitate, respectively called?
∆-9 desaturase
In adults where is de novo Faty acid biosynthesis restricted to?
The liver, adipose tissue and lactating breasts
What is meant by Acyl-CoA-dehydrogenase specificity?
Each acyl-CoA-dehydrogenase can bind a fatty acid chain of varying lengths
What is MCADD?
Medium chain Acyl CoA dehydrogenase deficiency
What type of diet should patients with MCADD sick to?
A high carbohydrate diet
What must patients with MCADD need it their illness manifests as apetite loss or severe vomiting?
i.v glucose to make sure their body is not dependant on fatty acids for energy
How can MCADD be treated?
Lifestyle adaptations
How are fats stored in the adipocytes?
As triglycerides
What are triglycerides broken down into?
glycerol and fatty acids using lipase
How many ATP does the generation of the Fatty Acyl CoA need?
2
What is the net gain of ATP per molecules of palmitoyl?
129 ATP
How many NADH and FADH2 does beta oxidation produce?
1 of each
What is TPI needed for?
Converstion of DHAP into G-3-P
What is the only fatal enzyme glycoltic enzymopathy?
TPI deficiency
