Glycolysis + Glucose oxidation Flashcards
what is glucose? what do we call it if we have too much/ too little? Where can it be stored? What is the most glucose-dependant organ?
C6H12O6
- Essential sugar for life! Most important source of energy.
- Ringed molecule made up of 6 carbons (hexose).
- Needs to be kept at a constant homeostatic level – controlled by hormones:
- Too much – hyperglycaemic
- Too little – hypoglycaemic (both serious conditions related to diabetes)
Can be stored as glycogen in liver and muscle
Most glucose-dependant organ? The brain
what is the normal range of glucose in the blood
Roughly 4 -6 mmol/l
(70 – 100mg/dl)
why can’t we just take glucose up how it is, why do we need GLUTs
- Issue: glucose is a charged (polar) molecule and glucose’s cell membrane is hydrophobic.
- so we need specialized glucose transporters: GLUTs
facilitate transport across a concentration gradient (no ATP needed!)
what are the important GLUTs u need to remember, and what does the Km of the GLUT indicate
Important GLUTs:
* GLUT1: expressed in all cells (low Km which means transporter has high affinity for glucose)
* GLUT2: expressed in liver and pancreas (high Km; so it acts as as sensor) – acts as a glucose sensor
GLUT 4: expressed in muscle and adipose cells (low Km) – controlled by insulin.
what is Km (Michaelis- Menten constant)
Km (Michaelis constant) of the enzyme, is an inverse measure of affinity. For practical purposes, Km is the concentration of substrate which permits the enzyme to achieve half Vmax. Vmax or a maximum velocity of an enzymatic reaction can be defined as the rate of the reaction at which the enzyme shows the highest turnover. Vmax, is the rate of the reaction under these conditions. Vmax reflects how fast the enzyme can catalyze the reaction.
what is facilitated diffusion and does it require energy from ATP
explain how glucose moves in via GLUT1
Facilitated diffusion does not require high energy molecules such as ATP. This type of diffusion uses channel proteins and carrier proteins to transport molecules across the plasma membrane. Facilitated diffusion involves the movement of molecules from areas of higher concentration to areas of lower concentration
Glucose enters the GLUT transporter which is embedded in cell membrane, glucose enters GLUT there’s a change in the GLUT shape. The glucose is going down the conc gradient so it doesn’t need ATP
there are 14 different isoforms of GLUT expressed in different tissues. For the following GLUTs describe 1) where they are found 2) if they are insulin dependent/independent 3) their Km and affinity
GLUT1, GLUT2, GLUT3, GLUT4 (which one is a glucose sensor)
GLUT1:
found in
*blood/all cells
*blood-brain barrier
*heart (lesser extent)
they’re insulin- INDEPENDENT
* low Km, high affinity
GLUT2:
found in
*liver
*pancreas
*small intestine
they’re insulin- INDEPENDENT
*high Km, low affinity= they’re GLUCOSE SENSORS
GLUT3:
found in
*brain
*neurons
*sperm
they’re insulin- INDEPENDENT
* low Km, high affinity
GLUT4:
found in
*skeletal muscle
*adipose tissue
*heart
they’re insulin- DEPENDENT
* low Km, high affinity
1) Why is exercise good for people with diabetes; in terms of GLUTS? (which GLUT is insulin dependent)
2) Explain how GLUT4 transports glucose in skeletal muscles
1) Exercise good for moving the GLUT4 (insulin dependent) transporters up to skeletal muscle cell membrane to help get glucose into the cell, muscles are working (need energy) so need glucose to supply ATP. Diabetics struggle getting glucose into the cells (they’re blood glucose levels are high so glucose stays outside the cells) so if you have diabetes + exercise then it will help getting it out blood and into the cells.
2) In skeletal muscles, most GLUT4 transporters are bound to vesicles inside the cell, so glucose cannot move inside.
Upon insulin signalling, these vesicle merge with the cell membrane, exposing the GLUT4 transporters and allowing glucose uptake.
Exercise also promotes this action (why exercise is good for diabetics)
what is glycolysis
N.B. U NEED TO DRAW THIS OUT ON PAPER
process which converts glucose to pyruvate
- first 5 steps require energy 2ATP (investment)
- last 5 steps (payback) generate
- 4 ATP
- 2 NADH (energy rich molecule)
- 2 pyruvate molecules (used in Krebs cycle to generate much more ATP)
1a) phosphorylation of glucose (hexokinase enzyme phosphorylates any 6C sugar)
1b) alternative: Glucokinase (only found in liver and pancreas)
2) Isomerization
3) Phosphorylation of fructose-6-phosphate
4) Breakdown of 6 Carbon ring to two 3 Carbon chains
5) Adding an inorganic phosphate (from the cytosol)
6) FIRST ATP IS PRODUCED
7) Shifting the phosphate
8) Dehydration
9) Another ATP is produced
control of phosphofructokinase I:
1)PFK1 is allosterically activated by what?
2)PK1 is inhibited by what?
- Phosphofructokinase 1 (PFK1) enzyme can be regulated by a number of molecules which will determine whether glycolysis moves forward, stops or backwards.
- PFK1 is allosterically activated by:
- High AMP levels (cell needs energy/ATP)
- Fructose-2,6-bisphosphate (F2,6P) produced from fructose 6-phosphate by an isoform of PFK1, called PFK2, an enzyme which is hormonally regulated.
- PFK1 is inhibited by products of glycolysis and the Krebs cycle:
- High ATP levels
Citrate (a byproduct of the Krebs cycle)
- High ATP levels
what do we know about phosphofructokinase II (PFK2)
Phosphofructokinase -2 is a bifunctional enzyme – it has kinase and phosphatase activities.
Insulin stimulates the kinase activity leading to fructose 2, 6 bisphosphate (stimulates PFK-1). Glucagon stimulates the phosphatase activity and gluconeogenesis
- Prior to generating our first ATP, we need to add a phosphate group from the cytosol (rather than from ATP as was happening before)
- The dehydrogenase enzyme catalyses the addition of a free phosphate to the glyceraldehyde producing a 3 carbon chain carrying 2 phosphate groups (a high energy molecule)
- As a by-product of this reaction, NAD+ is reduced to _________ plus a free proton (H+). This is super important!
- NADH is used later in the KREB’s cycle and electron transport chain to regenerate NAD+ which is needed to keep _______ going.
- NAD+ can also be regenerated by lactic acid produced from anaerobic breakdown of glucose
- Prior to generating our first ATP, we need to add a phosphate group from the cytosol (rather than from ATP as was happening before)
- The dehydrogenase enzyme catalyses the addition of a free phosphate to the glyceraldehyde producing a 3 carbon chain carrying 2 phosphate groups (a high energy molecule)
- As a by-product of this reaction, NAD+ is reduced to NADH plus a free proton (H+). This is super important!
- NADH is used later in the KREB’s cycle and electron transport chain to regenerate NAD+ which is needed to keep GLYCOLYSIS going.
- NAD+ can also be regenerated by lactic acid produced from anaerobic breakdown of glucose
Removal of a water molecule produces ________
______ is an important intermediary since it can also be produced by gluconeogenesis.
Enzyme is _______
(can be inhibited by fluoride ions – important for toothpaste!)
Removal of a water molecule produces phosphoenolpyruvate (PEP)
PEP is an important intermediary since it can also be produced by gluconeogenesis.
Enzyme is ENOLASE
(can be inhibited by fluoride ions – important for toothpaste!)
explain final step of glycolysis
- The last step of glycolysis produces the last ATP from PEP by the enzyme pyruvate kinase.
- The production of pyruvate is also important since it feeds into the next energy producing cycle – the Kreb’s cycle.
- This also is a substrate level phosphorylation of ATP from ADP.
- So what is the NET production or loss of energy (ATP) of glycolysis?
2ATP in: 4 ATP out: NET gain = 2ATP
How does glucose get into cells?
Glucose enters cells mainly through facilitated diffusion via glucose transporters (GLUTs). Different types of GLUTs are expressed in various tissues and are responsible for the transport of glucose across the cell membrane. In some cases, glucose entry is also regulated by insulin, particularly in muscle and adipose tissue (GLUT4).
