Metabolism with a focus on Glycolysis Flashcards
What is a metabolite?
- An intermediate or product of metabolism
- usually small molecules
What is the function of metabolites?
- fuel
- structure
- signalling
- regulatory effects on enzymes
- defence
- interactions with other organisms
How are metabolites linked?
Between metabolic reactions
What are metabolic reactions?
The life-sustaining enzyme-catalysed reactions that allow organisms to grow, reproduce, respond to changes in the environment and maintain structure
What is a metabolic pathway?
a sequence of chemical reactions undergone by a compound or class of compounds in a living organism (the product of one enzyme acts as the substrate for the next enzyme)
Is glucose taken in from the environment or synthesised in the body?
both
What is typically thought of as the universal energy provider?
glycolysis
How to you convert glycogen to glucose?
glucogenolysis
How do you convert glucose to glycogen?
glycogenesis
How do you convert glucose to pyruvate?
glycolysis
How do you convert pyruvate to glucose?
gluconeogenesis
How do you convert pyruvate to lactate or ethanol?
anaerobic respiration
What do you convert pyruvate to ATP?
TCA cycle and electron transport chain
Where does glycolysis occur?
cytoplasm
What are the two phases of glycolysis?
ATP consumption and ATP production
In glycolysis what does one glucose molecule get converted to using ATP?
1 x glucose-6-phosphate
What are the stages of glycolysis? (in general)
1 x glucose => 1 x glucose-6-phosphate (-ATP)
1 x glucose-6-phosphate => 1x fructose-6-phosphate (-ATP)
1x fructose-6-phosphate=> EITHER 2x dihydroxyactetone phosphate OR 2x glyceraldehyde-3-phosphate
2x glyceraldehyde-3-phosphate => 2x 1,3-diphosphoglycerate (2NAD+=> 2NADH)
2x1,3-diphosphoglyverate=> 2x 3-phosphoglycerate (2ADP=>2ATP)
2x 3-phosphoglycerate => 2x 2-phosphoglycerate
2x 2-phosphoglycerate => 2x phosphoenolpyruvate
2x phosphoenolpyruvate => 2x pyruvate (2ADP => 2ATP)
What happens in the glycolysis reaction that starts with 1x fructose-1,6-biphosphate?
Either 2x dihydroxyacetone phosphate or 2x glyceraldehyde-3-phosphate is produced.
Both of these can continue down glycolysis or can be used in a different pathway
What needs to happen to 2 x dihydroxyacetone phosphate of it is to continue down glycolysis?
Must be converted to 2x glyceraldehyde-3-phosphate
Can glucose diffuse directly across the cell membrane?
no
What are the two mechanisms to transport glucose into mammalian cells?
sodium monosaccharide co-transport=(sodium-dependent glucose transporter)
sodium independent facilitated diffusion
How does the sodium monosaccharide co-transport system work?
- energy requiring process
- transports glucose against conc gradient
- the transport of glucose is coupled to sodium which moves down conc-gradient
How does sodium-independent facilitated diffusion work when transporting glucose?
- mediated by a group of 14 glucose transporter isoforms (GLUT1-GLUT14)
- most isoforms operate on a conc gradient (only from high extracellular conc to low intracellular conc)
e. g
1. transport protein has a binding site for glucose outside the cell
2. glucose binds to the binding site
3. The binding causes the protein to change shape exposing glucose to the inside of the cell
4. glucose passes into the cell and the protein returns to original shape
Where is GLUT-1 found?
in erythrocytes (RBCs) and blood brain barrier
Where is GLUT-3 found?
neurons
Where is GLUT 4?
muscle and adipose tissue
Where is GLUT-2?
liver, kidney and pancreatic beta-cells
What is special about GLUT-2?
Can operate into and out of the cell to maintain appropriate blood glucose levels
What is needed to transfer glucose to glucose-6-phosphate?
- ATP (gets converted to ADP and H+)
- Mg2+
- Hexokinase
Why is the phosphate group added to glucose?
to make it more reactive
Other than the phosphate group, what is the difference between glucose and glucose-6-phosphate?
Glucose-6-phosphate is trapped inside the cell and can’t move out unless metabolic reactions occur whereas glucose can move in and out fo the cell
What are the two objectives of the phosphorylation of glucose?
- to trap glucose in the cell
2. to destabilise glucose to allow further metabolism reactions to occur
Other than glucose, what can hexakinase work on?
other hexose sugars
What is the role of the divalent metal ion (Mg2+) in the first step of glycolysis?
forms a complex with ATP to activate the ATP into losing a phosphate group
What is the conformation of hexokinase?
2 lobes
What happens to hexokinase when glucose binds?
-large conformational change
-two lobes move closer to each other when glucose binds
-the cleft between the lobes closes and glucose is surrounded by the protein
-only the hydroxyl group on the 6 carbon of glucose is available for reaction
(induced fit)
(substrate-induced cleft closing)
Why is the conformational change of hexokinase is important?
- the environment around glucose is highly non-polar which favours the reaction with the relatively non-polar ATP, specially the terminal phosphoryl group
- hydrophobic space allows ATP to diffuse to glucose (whereas water can’t)
- this ensures that the terminal phosphorylation group phosphorylates glucose and is not hydrolysed to ATP and phosphate
What is the enzyme for step 2? (glucose-6-phosphate => fructose-6-phosphate? And is it reversible?
phosphoglucose isomerase + yes
What happens in step 2?
H to lateral to CH2OPO3^- gets converted to CH2OH
What is step 3 of glycolysis?
conversion of fructose-6-phosphate to fructose-1,6-biphosphate using phosphofructokinase (PFK)
How is fructose-6-phosphate converted into fructose-1,6-biphosphate?
The H on the recently added CH2OH is removed and a phosphoryl group is added to form CH2OPO3^2- (covert ATP to ADP and H+)
What is step 4 of glycolysis?
Fructose-1,6-biphosphate is converted to two moles of either glyceraldehyde 3-phosphate (G3P) or dihydroxyacetone phosphate (DHAP) using adolase
Is step 4 reversible
yes
What is the structure of DHAP?
CH2OPO3^2- I C=O I CH2OH
What is the structure of G3P?
O=C-H I H---C---OH I CH2OPO3^2-
What is the enzyme that catalyses DHAP to turn into G3P?
triose phosphate isomerase (reversible)
How is G3P converted into 1-3-biphosphateglycerate? (step 6)
Phosphoryl group added to C=O
What is the enzyme required for step 6 and is anything else required?
glyceraldehyde-3-phosphate dehydrogenase
PO4^2-
NAD+
Is step 6 irreversible
no
What is the structure of 1-3 biphosphoglycerate?
O=C-OPO3^2- I H--C--OH I CH2OPO3^2-
What is step 7? And what enzyme does it use?
1-3-bisphosphoglycerate converted to 3-phosphoglycerate using ADP and phospholglycerate kinase (reversible)
What is the structure of 3-phosphoglycerate?
O=C-O^- I H--C--OH I CH2OPO3^2-
What is step 8?+enzyme involved
conversion of 3-phosphoglycerate to 2-phosphoglycerate using phosphoglycerate mutase (reversible)
What is the structure of 2-phosphoglycerate?
O=C-O^- I H--C--OPO3^- I H--C--H I OH
What is step 9?
2-phosphoglycerate is converted into phosphoenolpyruvate using enolase and releasing water (reversible)
What is the structure of phosphoenolpyruvate?
O===C–OH
I
H2C=C–OPO3^2-
What is step 10?
Phophoenolpyruvate is converted to pyruvate using pyruvate kinase and ADP
Is this reaction (step 10) reversible?
no
In glycolysis, how many reactions are reversible?
7
How many pyruvate molecules are made per glucose?
2
What is the structure of pyruvate?
O===C–OH
I
H3C-C===O
What is the net reaction of glycolysis?
glucose + 2ADP +2NAD^+ 2Pi (phosphate)
I
V
2 pyruvate +2ATP + 2NADH =2H^+ +2H2O
In what 4 ways can pyruvate be metabolised?
-Transamination to form alanine which can be used in gluconeogenesis
-Aerobic respiration to generate acetyl-coA and entry into TCA
-Anaerobic fermentation to generate lactate
-Anaerobic fermentation to generate ethanol
(some pyruvate can be applied to regenerate NAD+ from NADH (as cells are usually deficient during glycolysis)
What other sugars can enter into the glycolysis pathway?
fructose
mannose
galactose