Glycolysis (W1 6/12) Flashcards
1
Q
How does glucose get into cells? (From the pCAP)
A
- Glucose needs to get into cells, as that is where glycolysis happens.
- The problem is that glucose is not charged so doesn’t really diffuse into cells fast enough.
- It uses glucose transporters (GLUT 1-14) to get into cells by faciliated diffusion.
- Another method is co-transport.
Co-transport:
- Sodium concentrations are higher in the extra-cellular environment, so that gradient can be used to also get glucose into the cells. An important one in the intestine is the sodium glucose transporter (SGLT), which is the primary way glucose gets into the bloodstream from the intestine. Sodium goes allong its gradient.
Facilitated Diffusion:
- Different tissues express different GLUT to suit their function, and their energy demands.
- For example GLUT 1 is primarily involved in glucose uptake in RBC.
- GLUT 2 is used to get glucose in to the liver and kidney after a meal when blood glucose is high. Also when blood glucose is low, GLUT 2 allows glucose transport out of the kidney and liver into the blood stream.
- GLUT 3 gets glucose into neurons and brain cells.
- GLUT 4 is found on adipose tissue and skeletal muscle. After meal blood glucose goes up, insulin released and causes the number of available GLUT 4 to increase. This means adipose tissue will convert the excess glucose into fat, and skeletal muscle will convert glucose into glycogen.
2
Q
These are the LO’s dodo brain
A
- Describe the process of aerobic and anaerobic glycolysis
- Describe the enzymatic regulation of glycolysis
- Describe the production of ATP by substrate level phosphorylation
3
Q
What are the main steps in getting energy from food?
A
- Fats, carbs and proteins are oxidised. The electrons they lose are used to make ATP.
- Complex molecules like carbs, proteins and fats are hydrolysed into monosaccarides, amino acids and glycerol, fatty acids.
- They are then converted into acetyl coA
- Acetyl coA is oxidised to produce ATP
4
Q
What does catabolic and anabolic mean?
A
- Catabolic: break down, release energy
- Anabolic: build up, need energy
5
Q
Why do we need energy?
A
- Muscle contraction
- Active Transport
- Biosynthesis (the production of complex molecules)
- Cellular processes
- Adaptive thermogenesis (producing heat)
6
Q
Define metabolism?
A
The chemical processes by which cells produce the substances and energy needed to sustain life.
7
Q
Define glycolysis
A
The oxidation (loss of electrons) of glucose to form ATP.
8
Q
What is b-oxidation?
A
oxidation of fatty acids
9
Q
What is the Krebs cycle / Tri-carboxylic acid cycle (TCA)
A
A series of chemical reactions used by all aerobic organisms to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins.
10
Q
Important anabolic (build up, need energy) pathways?
A
- Glycogenesis = production of glycogen from glucose
- Gluconeogenesis = production of glucose
- Fatty acid synthesis = Synthesis of fatty acids
11
Q
Describe key facts about glycolysis
A
- Occurs in the cytoplasm of cells
- Employed by all tissues.
- Glycolysis converts glucose to pyruvate.
- If oxygen: then pyruvate then goes to the link reaction/ oxi. decarboxylation, krebs reaction and oxidative phosphorylation.
- If no oxygen: lactate is made, as it regenerates NAD, so glycolysis can repeat and make ATP.
- Glycolysis has a dual role: oxidation of glucose to generate ATP and provision of building blocks for anabolic reactions. Excess acetyl coA is converted into FA/tag/VLDL.
- In liver and adipose tissue main function is to produce precursors for FAT (Triacylglyceride) synthesis.
12
Q
What are the steps in aerobic glycolysis?
A
Net:
2 x Pyruvate
2 x ATP
2 x NADH
13
Q
How is glycolysis regulated?
A
- The regulation of glycolysis varies from tissue-tissue.
- In most tissues the main role of glycolysis is to produce ATP but if cell energy levels are high glycolysis is inhibited.
- In the liver main role is production of precursors of triacylyglycerides stores and glycolysis will proceed even though cell energy levels are high.
There are three key enzymes involved in regulation of glycolysis:
- Hexokinase (other tissues) or Glucokinase (liver) catalyses the coversion of glucose into phosphorylated glucose/ AKA Glucose-6-Phosphate
- Phosphofructokinase 1 (the most important regualtory enzyme) unfortunately just have to learn this: catalyses fructose-6-P to fructose-1,6-BP.
- Pyruvate kinase (regulated in the liver) catalyses the final reaction of glycolysis: phosphoenolpyruvate → pyruvate.
14
Q
Hexokinase vs Glucokinase
A
- Hexokinase (other tissues) or Glucokinase (liver) catalyses the coversion of glucose into phosphorylated glucose/ AKA Glucose-6-Phosphate
- Hexokinase:
- has a high affinity (the degree of binding) for glucose
- has a low Km with glucose. This means that even a small amount of glucose allows hexokinase in tissues to acheive half it’s Vmax
- It has a low Vmax (the point all the hexokinase proteins are saturated with glucose)
- Hexokinase in tissues is inhibited by G6P (made when cell energy levels are high).
- Glucokinase:
- has a low affinity for glucose
- So high Km, which means a large amount of glucose is required to allow glukokinase to acheive half it’s Vmax.
- It has a high Vmax.
- Not inhibited by G6P glycolysis proceeds even when cell energy levels are high.
15
Q
PFK1 Regulation
A
- Phosphofructokinase (PFK1) coverts fructose 6 phosphate to fructose 1,6 bisphosphate.
- PFKI is the most important regulatory enzyme of glycolysis, because it is a rate limiting step: It is inhibited by ATP (cell energy levels high), so stops glycolysis. It is stimulated by AMP (made when cell energy levels low) so know glycolysis is needed.
- The most potent activator of PFK1 is fructose 2,6-bisphosphate. It activates PFK1 even when ATP levels are high. Fructose 2,6-bisphosphate is produced by liver in well fed state.
