L3. Fatty Acid and Glucose Oxidation Flashcards
LO
Beta oxidation:
- Identify the carbon atoms in fatty acids based on different codes of nomenclature
- Explain how fatty acids are transported into the cytoplasm, trapped, and then transferred into the mitochondrial matrix
- Explain the biochemical features of CoA that enable it to do its job
- Appreciate the role played by FAD and NAD in FA-CoA oxidation
- Understand the steps within the process of beta-oxidation
Glycolysis
- Give a strategic overview of glycolysis
- Discuss the process of glucose transport into the cytoplasm and trapping within the cell
- Outline the energy investment and return stages of glycolysis
- Identify the different fates of pyruvate and understand when each is required or desirable
Krebs cycle
- Understand the position of the Krebs cycle in catabolism
- Outline the overall process and strategy of the Krebs cycle
- Describe the major intermediates and regulatory steps in the Krebs Cycle
H/e- Strippers and Carriers
NAD+ - > NADH:
-CH2-CHOH- to -CH 2-C=O
- Creates a double bond between C&O
FAD - > FADH2:
–CH2-CH 2- to –CH=CH-
- Creates a double bond between C&H
Both in limited supply
Beta oxidation
- Creates lots of NADH and FADH2
- Zero ATP created
- Builds up lots of ac-CoA
Fatty Acid Oxidation (Beta-Oxidation):
FA from blood into matrix- trapping and transporting
- FA is hydrophobic and can diffuse from blood into the cytoplasm
- Once FA is in the cytoplasm, FA binds to coA to create FA-CoA to trap it inside
To get the FA into the mitochondria, it must travel through another membrane
- The CoA is removed and a carnitine molecule picks up the FA
- Carnitine takes the FA into the matrix from the cytoplasm
- Carnitine is swapped with CoA to trap it inside again
Fatty Acyl-CoA then undergoes mutliple rounds of Beta-Oxidation (1 round = 1 NADH, FADH2 & ac-CoA)
Transport of FA
- FA cannot freely float in blood as its hydrophobic, therefore it is loosely associated with albumin
- Can passively diffuse into a cell with a lower FA concentration
- Once inside the cell FA-binding proteins pick up the FA
- FA is then trapped within the cell
Trapping of FA
- FA uses ATP, (oxidising it all the way to AMP) to bind to CoA
- Forming Fatty acyl-CoA (FA-CoA)
- This ‘activates’ the FA
Transport of FA (Mitochondria)
- Carnitine acyl-transferase 1 & 2 (carnitine) help the FA-CoA get into the mitochondria from the Cytoplasm
CAT-1 = FA-CoA (+Carnitine) .> FA-carnitine (+CoA)
CAT-2 = FA-Carnitine (+CoA) .> FA-CoA (+Carnitine)
Carnitine can diffuse in and out of the matrix to cytoplasm to collect new FA-CoA
[heft]
First step of Stripping: Beta Oxidation
- FAD oxidises CH2-CH2 into CH=CH and is reduced on the beta-carbon into FADH2
- This new double bond is then hydrated, converting into a CHOH
- CHOH can then be oxidised by NAD+
Second Step of Stripping in beta oxidation
- NAD+ oxidises the CHOH group into CH2-C=O and is reduced to NADH
- A CoA enxyme cuts (cleavages) the FA chain to release an Acetyl-CoA group and a C14-FA-CoA group
- C14-FA-CoA can undergo beta oxidation again, repeating loosing 2C every round.
- Each C16 can undergo beta oxidation 7x to get 8x ac-CoA
[heft]
Glycolysis
- Starts with glucose uptake from blood to cytoplasm
- Once glucose has entered the cell, hexokinase adds a phosphate to the glucose by using an ATP (preventing the glucose from diffusing back out)
- This turns the glucose into Glucose-6-Phosphate (G6P).
- G6P can’t leave the cell
Glucose cannot diffuse in, uses GLUT transporters
- GLUT-1 = always bringing in glucose
- GLUT-2 = Liver and pancrease (blood-glucose regulating, most active)
- GLUT-4 = Muscle and adipose tissue (insulin sensitive)
Early Glycolysis (investment phase)
- G6P undergoes an isomeric reaction
- Turns into Fructose-6-Phosphate
- Using an ATP, Phosphofructokinase adds a phosphate to convert it into ‘Fructose 1-6-Bisphosphate’
- Fructose 1-6-Bisphosphate splits to form 2C sugars
Uses 2x ATP
Late Glycolysis (Return Phase)
- The 2C molecules are oxidised to Pyruvate, reducing NAD+ into NADH
- During this process 4x ATP are produced
- Therefore a total of 2ATP gained
- NADH is released into the cytoplasm and cannot reach the ETC in the mitochondria to drop off its ‘cargo’
- Therefore glycolysis cannot keep converting glucose straight to pyruvate, it will run out of NAD+
- To combat this, pyruvate is reduced to lactate, oxidising NADH, allowing glycolysis to continue
Pyruvate can also go into the mitochondria and interact with an enzyme
- Pyruvate is decarboxylated and reduces an NAD+ into NADH
- The 2C remaining molecule is ac-CoA
The Krebs Cycle
C-I-K-S-S-F-M-O
- ac-CoA entres the krebs cycle
- ac-CoA binds to Oxaloacetate
- Citrate is created, and hydrated
- Isocitrate is formed, and decarboxylated and oxidised, reducing NAD+
- α-Ketoglutarate is created, and decarboxylated and oxidised, reducing NAD+
- Succinyl-CoA is formed, and rearranged by an enzyme to produce GTP(ATP)
- Succinate is formed, and is oxidised, reducing FAD
- Fumarate is created, and hydrated
- Malate is formed, and oxidised, reducing NAD+
- Oxaloacetate is formed, ready for ac-CoA to bind
[heft]
