Lecture 13 Information Flashcards
Glycolysis overall reaction
Glucose + 2ATP + 2 NAD+ => 2 Pyruvic acid + 2 NADH + 2ATP + 2H2O
How many phases and steps are in glycolysis?
2 phases and 10 total steps
Where does glycolysis take place?
in the cytoplasm
Step 1 of glycolysis
convert glucose to glucose 6-phosphate
hexokinase accomplishes this
requires ATP
highly irrevisible
Step 2 of glycolysis
isomerize glucose 6-phosphate to fructose 6-phosphate
Step 3 of glycolysis
convert fructose-6 phosphate to fructose 1,6 bisphosphate
phosphofructokinase-1 accomplishes this
requires ATP
highly irreversible
Which step guarentees that glucose will go through glycolysis?
step 3
can no longer use fructose-6 phosphate / glucose for anything else
Step 4 and 5 of glycolysis
produce glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (3 carbons with phosphate)
triosephosphate isomerase converts dihydroxyacetone phosphate to glyceraldehyde 3-phosphate
happens very fast
Step 6 of glycolysis
glyceraldehyde 3-phosphate gets 2 phosphates added (oxidized) to convert to 1,3-bisphosphate
in this step, NAD+ is reduced to NADH
glyceradehyde 3-phosphate dehydrogenase accomplishes this
Step 7 glycolysis
remove a phosphate from 1,3-bisphosphate to make 3-phosphoglycerate
2 ADP is converted to 2 ATP
phosphoglycerate kinase accomplishes this
Step 10 of glycolysis
phosphoenolpyruvate (PEP) is converted to pyrvuate
converts 2 ADP to 2 ATP
pyruvate kinase accomplishes this
What happens to pyruvate?
has energy contained in 3 carbons that can still be used for energy
pryuvate moves to the Krebs/Citric Acid Cycle
Which steps drive glycolysis forward?
Steps 1, 3, and 10
all steps have large negative ∆Gs
How do more unfavorable steps of glycolysis take place?
Change the concentrations of intermediates and substrates to make ∆G favorable
Hypoxic
low oxygen in cell
What does hypoxia trigger?
an increase in glycolytic enzymes which increases the rate of glycolysis
Warburg effect
even after cancer cells develop blood flow and have O2 they still use just glycolysis as an energy source
Why would cancer cells want to keep running glycolysis?
glycolysis releases hexokinase which moves to the mitochondria to stop apoptosis inducing factors from being released
factors such as cytochrome c
What molecule might be helpful in treating cancer cells?
DCA
DCA makes it more likely that a cell will run glycolysis and then run the Krebs Cycle/ETC
activates pyruvate dehydrogenase
Type I diabetes
inability of pancreas to produce enough insulin to trigger the decrease of blood-glucose concentration levels
Type II diabetes
inability of target cells to pick up insulin signals
receptors are not as sensitive to insulin
What does insulin trigger?
a pathway to place more GLU4 receptors on the cell surface
GLU4 receptors can take glucose out of the blood and into the cell
What do high blood glucose levels do?
increase blood pressure
What do low blood glucose levels do?
cause hypoglycemia and passing out since brain is not getting glucose
What is glucose metabolism limited by?
how much glucose we can take into our cells
What happens when the cell does not have enough glucose?
cell relies on other sources of energy like lipids/fatty acids through beta-oxidation
What is a negative side effect of using lipids/fatty acids instead of glucose as energy source?
Beta-oxidation produces ketone-bodies as a result
too many ketone-bodies in the blood can lower the pH of blood and trigger keto-acidosis
Where does glucose come from?
break off monomers from starch / glycogen chains
break down sucrose into fructose/glucose
gluconeogenesis
How can fructose be used in glycolysis?
hexokinase can convert it to fructose 6-phosphate to be used
What happens to carbons from glucose?
they are greatly oxidized to CO2
the energy from this oxidation goes to the ETC
What is a problem of too much glycolysis in anaerobic conditions?
produce a lot of NADH and deplete our NAD+ reservoirs
How do we replace our NAD+ reservoirs?
through fermentation
Different types of fermentation
lactic acid and yeast (ethanol)
Lactic acid fermentation
pyruvate is reduced to lactate
NADH is oxidized to NAD+
lactose dehydrogenase accomplishes this (substrates are NADH and pyruvate)
Difference between lactic acid and Alcoholic fermentation?
lactic acid is one step and Alcoholic is 2 steps
Alcoholic fermentation
first, pyruvate is converted to acetaldehyde by pryuvate decarboxylase
second, acetaldehyde is reduced to ethanol through alcohol dehydrogenase
in second step, NADH is oxidized to NAD+
What happens when glucose levels are low?
have to produce glucose through gluconeogenesis
Where does gluconeogenesis take place?
the liver
Types of substrates for gluconeogenesis?
lactate, triacylglycerol and CO2
Gluconeogenesis step 1
use bisphosphate and pyruvate to produce oxaloacetate
First chokepoint of gluconeogenesis
convert oxaloacetate to PEP by using GTP
PEP carboxykinase and pyruvate caroxylase accomplish this
weird trip through the cytosol to mitochondria back to the cytosol
Second chokepoint of gluconeogenesis
convert fructose 1,6 bisphophate to fructose 6-phosphate
use fructose 1,6-bisphosphatase
this is reversing the highly irreversible step 2 in glycolysis
Third chokepoint of gluconeogenesis
convert glucose 6-phosphate to glucose
glucose 6-phosphatase does the opposite of hexokinase
we do not use or produce ATP here, just remove the phosphate
Cori Cycle
fermentation meets gluconeogenesis
lactic acid from fermentation can be moved from the muscle into the liver cells
in the liver, the lactate can be converted into pyruvate and go through the process of gluconeogenesis
The Pentose Phosphate Pathway (PPP) overview
creating pentose sugars from glucose to be used in DNA and RNA
takes place in the cytosol
Steps of PPP
start with glucose 6-phosphate and use 2 NADP+ to oxidize twice to produce ribose 5-phosphate
NADP+ is reduced to NADPH
NADPH
produced in the PPP
can reduce the reactivity of free radicals and oxygen species
Ribose 5-phosphate
produced by PPP
plant cells use it in chloroplasts
other cells use it as an intermediate to produce nucleotides, coenzymes, DNA and RNA (expect to find in cells that are rapidly dividing)
Favism
people with glucose 6-phosphate dehydrogenase deficiencies can get very sick when they eat fava beans since they do not produce enough NADPH
Fava beans
contain an oxidizing molecule that NADPH normally reduces
Why does favism prevail?
individuals with this disease are protected from malaria
paraise does not grow well in glucose 6-phosphate dehydrogenase deficient cells
What are 3 levels of control to regulate glucose and gluconeogenesis?
enzyme control, hormones, and transcription
What are the types of hormone control to regulate glucose / gluconeogenesis?
hexokinase bypass, PFK1 bypass, pyruvate kinase bypass
Hexokinases in muscle cells versus liver cells
in muscle cells, hexokinase 4 has a LOW Km so glucose will be used even without large concentrations
in liver cells, hexokinase 1 has a HIGH Km so glucose will only be used at high concentrations
additionally, muscle cells hexokinases are inhibited by the product G6P and liver cells are not so they can work longer
How is glucokinase regulated in the liver?
regulated through glucose concentrations
with high concentrations, will go through glycolysis
might not go through glycolysis with low concentrations
GKRP
“bear hug” protein
takes glucokinase out of commission and places glucokinase in the nucleus
stimulated by the intermediate fructose 6-phosphate
signals that we have low glucose levels and don’t want to go through glycolysis
Phosphofructokinase 1 (PFK1) regulation
allosterically inhibited by ATP and citrate
ATP is both a substrate and an end product
citrate is a component of the Krebs Cycle and signals that you do not need to keep going through glycolysis
Gluconeogenesis enzyme FBPase-1
inhibited by AMP which signals that there is not much energy in the cell (AMP > ATP)
prevents gluconeogenesis from taking place
need to use glucose to make fuel
Insulin
inactivates FBPase-2 and activates PFK-2
stimulates glycolysis and inhibits gluconeogenesis
take sugar to use for ATP
Glucagon
activates FBPas-2 and inactivates PFK-2
inhibits glycolysis and stimulates gluconeogenesis
FBPase-2
when activated, stimulates gluconeogenesis
PFK-2
when activated, stimulates glycolysis
What type of receptors does insulin bind to?
tyrosine kinase receptors
For every one glucose molecule how many pyruvate molecules do we have?
2 pyruvate for every 1 glucose
What happens to glucose’s carbons at the end of glycolysis?
they are oxidized to Co2
The extra energy goes into the ETC by placing placing electrons on NADH
2 examples of ketoacids
acetoacetate and B-hydroxybutyrate
How are ketone bodies used at low concentrations?
low concentrations can be used by the brain
when concentrations are too high like in diabetes, trigger ketoacidosis and can have trouble transporting on hemoglobin
Active site versus allosteric site in PFK-1
Active site has a high affinity for ATP in order to run glycolysis
Allosteric site has a low affinity for ATP because only in high concentrations of ATP do we want to inhibit PFK-1
What turns on PFK-1?
ADP and AMP since they indicate that there is not a lot of ATP in the cell
Fructose 2,6-bisphosphate
Activates PFK-1 but inactivates FBPase-1 (which is used in gluconeogensis)
Turns on glycolysis and turns off gluconeogensis
What produces fructose 2,6-bisphosphate?
PFK-2
Insulin and regulating glycolysis
Insulin activates PFK-2 which produces fructose 2,6 bisphosphate which will turn on glycolysis through activating PFK-1
Glucagon and regulating glycolysis
Glucagon inactivates PFK-2 so fructose 2,6 bisphosphate will not be produced and gluconeogenesis can take place
Transcription factors
regulate the amount of enzymes we produce and therefore can regulate the amount of glycolysis that can take place
