Biomolecules - Krebs Cycle + Fat Metabolism

Question 1

Regulation of Krebs cycle

Answer 1

• Glycolysis in cytoplasm, Krebs cycle in mitochondria
• Uses of acetyl coA include entry into Krebs cycle and production of fatty acids when ATP levels are high
• there is no hormonal regulation
• main form of regulation for the Krebs cycle is allosteric regulation. For the entry into the cycle, it’s allosteric regulation of the pyruvate dehydrogenase enzyme. A low energy state of the cell, with more AMP will alert the body to produce more acetyl coA. A higher energy state with more ATP, will cause reduced production. Fatty acids inhibit the production of acetyl coA because if there’s a lot of them, the body doesn’t need to produce more acetyl coA. The (oxaloacetate to citrate), (isocitrate to alpha ketoglutarate) and (ketoglutarate to succinyl coA) have large negative delta Gs and so are good targets for regulation. NADH inhibits all three of these. ATP inhibits the first two. Citrate and succincly coA can perform negative feedback. ADP is an activator and it activates the same enzymes that ATP inhibits. Calcium is an activator for the enzymes between the last two.
• another mode of regulation is looking at substrate availability. If there’s less acetyl coA, NADH and FADH2 production will reduce.

Question 2

Regulation of oxidative phosphorylation

Answer 2

Functions: to produce a lot of ATP and to be a common end pathway of aerobic respiration (even when non glucose macromolecules are used to give energy, they go through this step)

• there is no major hormonal or allosteric regulation for this
• levels of ADP is normal the limiting factor and is most likely to be regulated. If ADP is high, then the ETC will go faster. If ATP is high, the body will slow the ETC

Question 3

Apoptosis and necrosis

Answer 3

Apoptosis is controlled/programmed cell death and caspase catalysed. Necrosis is more uncontrolled and is normally in respond to extreme trauma or infection.
Inducing the cell to undergo apoptosis
- DNA damage
- development: killing tissue between our fingers when embryo
- infection (viruses)
- stress (if cell to cell interactions are disrupted)
- ROS (reactive oxygen species)

*mitochondria initiate apoptosis. The outer membrane becomes more permeable to allow cytochrome c to enter the cytoplasm and activate caspases. The proteins that regulate this permeability are in the BCl2 family - pro-apoptosis and anti-apoptosis.

Question 4

Fats

Answer 4

Fats are the main energy storage fuel in the cell.

Triacylglycerides are very good storage forms of energy because they are energy rich, relatively inert and they have no large functional role (better than proteins). They’re also very hydrophobic meaning they don’t have water weight

Question 5

Fatty acid synthesis

Answer 5

Main ways we get fat: diet (triacyglycerides to chylomicron to blood), adipose cells, liver (glucose to fatty acids to triacyglycerides to VLDL to blood). The hydrolysis of ATP is coupled to fatty acid synthesis to make it favourable.

Citrate shuttles from the mitochondria to the cytoplasm. An enzyme breaks it into acetyl coA And oxaloacetate (converted to pyruvate and shuttles back to the Krebs cycle; we oxidise oxaloacetate and reduce NADP+ to NADPH)

Question 6

Fatty acid oxidation

Answer 6

95% of energy in a triacyglyceride is from the fatty acid chains.
The enzymes needed for fatty acid oxidation are in the mitochondrial matrix

Question 7

Starvation

Answer 7

To maintain glucose levels, we break down glycogen through gluconeogenesis. Amino acids can be converted to a lot of the necessary intermediates in the Krebs cycle, forming oxaloacetate which is needed for gluconeogenesis. Fatty acids can produce acety coA and that is useful in the cycle, but the acetyl coA doesn’t enter the pathway for gluconeogenesis.

During prolonged starvation, our body tries to save our protein and not spend them making glucose. Instead, the body turns to ketones. It shunts the excess acetyl coA produced into ketones in the liver, which can be converted back to acetyl coA and used in the Krebs cycle. There’ll be less pressure to undergo gluconeogenesis, so most protein degradation happens in the first few days of starvation

Question 8

Amino acid metabolism

Answer 8

Amino acids in the liver can be used for protein synthesis and glucose or fatty acid synthesis stored as glycogen and triacyglycerides. Ketogenic or glucogenic refers to whether the backbone of the amino acid feeds back into glucose or fatty acid synthesis.

Lysine and leucine are exclusively ketogenic.