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Why do we have control?
we don't want pathways running all te time--> we turn them on and off
What are the three ways of protein control?
- 1) allosteric control (most rapid method)
- 2) reversible covalent modification (phosphorylation)
- --> longer because you have to take in a kinase
- 3) control amount of enzyme; level of transcription (slowest response)
In glycolysis, what are the targets of control? Which is the most important?
- phosphofructokinase: the most important step because it is committed (on/off)
- pyruvate kinase
- hexokinase and pyruvate kinase are regulatory
How do you turn phosphofructokinase off in muscle?
- controlled allosterically; responds to high ATP levels
- Also, due to lower pH as a result of lactic acid, aTP turns i off.
Why does ATP inhibit phosphofructokinase?
ATP binds to allosteric sights on phosphofructokinase, causing a conformational change in which the enzyme has a lower affinity for the substrate. There's a lot of energy.
What are ATP's effects inhibited byin phosphofructokinase?
- reversed by high levels of AMP
- adenylate kinase can take two ADP molecules and convert it into ATP and AMP.
This occurs when a cell is desperate for ATP
AMP turns it on
Affecting phosphofructokinase causes what to be affected?
- The flow into glycolysis (controlled by hexokinase)
- the flow out of glycolysis (controlled by pyruvate kinase)
A buildup of fructose 6-phosphate causes a buildup of glucose 6-phosphate, which it is in equilibrium with. This clogs up the active site of hexokinase, turning it off (in muscle)
Glucose that gets into muscle cells can now get back out and go to other places
What is pyruvate kinase controlled by?
it is inhibited by high levels of ATP--> slow down the enzyme
An amino acid made from pyruvate is alanine. If in high concentration, pyruvate kinase slows down
In the liver, phosphofructokinase is controlled how?
It never deals with pH change
- inhibited by ATP in the same way
- Also inhibited by citrate in CAC, which can lead into the cytoplasm, signifying that building blocks are present, enhancing ATP production
What else is phosphofructokinase controlled by in the liver?
fructose 2,6-bisphosphate (F-2,6-BP)
Glucose levels high in bloodstream; buildup of fructose 2,6-bisphosphate; activates phosphofructokinase in liver
In the liver, there is __, which is the last place gulcose goes becuase this is how glucose stores the liver for later.
How is hexokinase controlled in the liver?
can't be inhibited by own product. It'll keep churning out G6P--> goes to be converted to glycogen
- in liver there is the L type
- reversible phosphorylation
- blood glucose levels low--> phosph kinase--> turn it off in liver--> glucose can escape and be used elsewhere
glucose high--> dephosphorylation--> glucose doesn't get away
Glucose can be made into __, which can be reversible. However, once __ is covnerted to __, it cna't go back.
Acetyl CoA-> gets converted to __ and __.
- Acetyl CoA
Because acetyl CoA can't be reversed, what happens ?
control is in this area by the pyruvate dehydrogenase complex
Explain the control of pyruvate dehdrogenase complex.
- Enzyme E1 can be reversibly phosphorylated.
- Kinases activate it by high levels of NADH, acetyl CoA, and ATP; all three say that energy content in the cell is okay
- shut off the omplex--> let pyruvate do something else
How is the CAC controlled?
- Isocitrate dehydrogenase
- alpha-ketoglutrate dehydrogenase complex
allosteric changes from ATP and NADH
high ATP and NADH turns it off
high ADP turns it on
Alpha ketoglutarate dehydrogenase complex
responds to same as pyruvate dehydrogenase complex
- NADH, ATP, or its production
- high levels shut off
How did they measure the production of ATP?
they measure O2 consumption for results
control oxidative phosphorylation; flow of e- through ETC dependent on ADP levels
What stimulates O2 consumption?
once ADP is added, O2 consumed at large rates
need for ATP controls oxidative phosphorylation
high ATP leads to flow of electrons in ETC
What is brown fat?
adipose cells with a lot of mitochondrion in them; found in animals that like to hibernate
What do the mitochondria in brown fat do?
these mitochondria produce Hydrogen gradient
if you're hibernating, proton gradient not used for ATP. You need to stay warm
A group of proteins (UCP)= uncoupling proteins
WHat do UCPs do?
they uncouple the link ebtween electron transport and use of hydrogen gradient to make ATP
allows buildup an flow of Hydrogen ion, making heat
proton gradients power?
- flagellar rotation
- active transport
- electron potential
- heat production
- NADPH synthesis