Lecture 1 Glycolysis Flashcards
What is AMP
AMP + P -> ADP, ADP + P = ATP
What is creatine phosphate
its high energy molecule stored in muscles used in the rapid production of ATP in times of high energy demand. creatine in the body makes creatine phosphate
Why is glycolysis a core metabolic pathway
- Provides rapid energy in times of no oxygen
- acts as intermediate for other processes
How should glycolysis enzymes balance?
Balance between energy needs of the cell and making precursors for other processes?
When should glycolysis be turned on and off?
To make other precursors?
- Not enough precursors: make more
- Enough precursors: glycolysis can slow down
Energy:
Low energy -> more glycolysis
AMP is the low energy status
ATP is the high energy status
What is the negative and postive control of regulatory step in step 1?
Negative regulator: Glucose 6-P (negative feedback)
What is the negative and postive control of regulatory step in step 3? Frutose-6-P -> Frutose 1-6 bisphosphate?
(+): F-2,6-BP
(+): AMP
(-): ATP
(-): Citrate
(-): H+
What is the negative and postive control of regulatory step in step 10? phosphoenol pyruvate -> pyruvate?
(+): F-1,6-BP (feedforward)
(-): ATP
(-): Alanine
How do regulators of control point affect the enzyme?
It affects the enzyme kinetics - making the reaction go slower or faster.
How do different tissues control the pathway differently?
Different tissues control the pathway in different ways
How is glycolysis in the muscles regulated?
How is phosphofructokinase regulated?
How is hexokinase regulated?
How is pyruvate kinase regulated?
It is regulated to meet energy needs.
Primary regulation is by ATP/AMP ratiods
Energy needs change rapidly
- PFK is regulated by ATP and AMP
- Hexokinase is regulated by negative feedback
- Pyruvate kinase is regulated by ATP and feedforward activation
How is PFK controlled?
ATP and AMP compete for binding to the regulatory site
How does ATP/AMP binding affect PFK?
Glycolysis in muscles is tightly linked to
The need for ATP
When does Glycogen enter glycolysis
via Glucose-6-p
How is glycolysis in the liver regulated? How is PFK, Hexokinase/glycokinase regulatoed, pyruvate kninase
The Liver has more diverse biochemical functins than the muscle (detoxification, maintianing blood-glucose).
PFK, in addtion to ATP, is regulated by intermediates of other pathways.
Hexokinase and glucokinase (isoenzymes)
Pyruvate kinase in the liver is regulated allosterically and by covalent modification.
Regulation by metabolic intermedites, as well as hormonal regulation
How is glycolsyis in the liver regulated?
by other metabolic intermediates/hormal
How is PFK regulated via ATP/AMP?
Allosteric binding
Why does glycolsyis in liver control need to override ATP regulation?
Because it doesnt experience sudden changes in ATP/ADP
How is pyruvate kinase regulation different in muscles vs. liver
pyruvate is regulated by ATP/AMP (allosteric). in the liver, it is also phosphorylated
Difference between hexokinase and glucokinase
Difference between Glucagon and Glycogen
Glucagon: is the hormone
Glycogen: stored sugar
When is glucagon/insulin acgivated
Glucagon is activated when blood sugar is low. Liver releases glucose (from glycogen)
insulin is triggered when blood sugar is high. Triggers cells to Absorb some of the glucose from the blood. In the liver (glucose -> glycogen)
How is PFK regulated in the liver
Liver: does not respond to ATP quickly -> regulate by metabolic intermeidates
Citrate (-): indicate we have enough precursors -> slows down glycolysis
F-2,6-BP (+): production of F-1,6-BP -> signals theres sugar in the blood -> glucose should speed up
Write the full equation for glycoslysis
What is Vmax
Maximum velocity of a reaction
What is Km?
COncentration of substrate that permits an enzyme to achieve half of its Vmax. Its a measure of affinity. The higher the Km, the lower the affinity
What does higher Km mean?
Lower affinity
How is PFK regulated in the muscles
By allosteric modification of ATP/AMP.
High ATP -> ATP binds (reduces affinity of PFK for Fructose-6-P) _> slows down glycolysis
Low ATP -> AMP binds, does not inhibit -> displaccces ATP from binding -> speeds glycolysis up (cells need energy)
How is hexokinase regulated in the muscles
Glucose-6-p (negative feedback)
so when glucose-6-p goes up -> slows down HK
Pyruvate Kinase
(+) F-6-P -> activiates PK -> speeds glycolysis
(-) ATP -> slows down glycoslys
What happens after a carbohydrate rich meal?
Glucose levels go up -> F-2,6-BP signals go up -»> push glycolysis.
But when theres a lot -> citrate build up -> (-) glycolysis
How is pyruvate kinase in the liver regulated?
By phosphorylation.
So when glucose levels in the blood are low -> want to stop glycoslysi so brain can use it.
Phosphorylate the Pyruvate kynase -> slows down activity.
when glucose levels are high -> can phosphorylate it to speed up activyt
It is also regulated allostericall
What is glucokinase? What is it responsible for? When is it active?
An isomer of hexokinase, mainly responsible for phosphorylating glucose in the liver. Active whne glucose levles are high
Glucokinase vs. Hexokinase
- Glucokinase has lower affinity than Hexokinase (only active at high concentrations of glucose)
- GK has high specificity for glucose
- Glucose is not inhibited by Glu-6-pi
When conc of Glu in the blood is high, having glucokinase in the liver can help remove the sugar from the blood and channeled into the liver
Application of glucokinase/pharmaceutical-wise?
Allosteric enzymes which can increase affinity of glucokinase to help remove sugar from blood
Are glucokinase/hexokinase allosteric enzymes?
Yes
SLide 63
How do hormones: glucagon and insulin coordinate metabolic pathways?
Insulin (pancreas): when blood sugar levels are high -> signals cells to absorb sugar frm the blood.
Liver: glucose -> glycogen
Glucagon (pancrease): when blood sugar levels are low ->secretes glucose. Liver: glycogen -> glucose
How to control a regulatory step?
1.Amount of enzymes
Can be controlled by gene expression,
protein degradation, etc.
2. Enzyme catalytic activities
Allosteric control, reversible covalent
modification, hormonal regulation,
energy status of the cell.
3. Substrate availability and accessibility
Tissue, cellular compartment
What is a regulatory step?
Rate determining step
Not reversible
first step that commits the flux into a psathay