Glucose Metabolism (complete) Flashcards
What is the primary source of glucose between meals
glycogenolysis of the hepatic glycogen
What are the three sources of glucose that increase blood glucose
- dietary carbohydrates
- glycogen
- Lactate, amino acids, Glycerol
What is the process of turning glycogen into glucose calles
glycogenolylsis
what is the process of turning glucose in to glycogen called
glycogenesis
what is the process of turning lactate, amino acids, and glycerol into glucose called
gluconeogenesis
What are the two processes of glucose storage (these decrease blood glucose)
- glycogenesis
2. lipogenesis
what is lipogenesis
the formation of triacylglycerols in the liver
Where are the two most significant tissues that store glycogen
- the liver
2. skeletal muscle
For what purpose does skeletal muscle do glycogenolysis
it does glycogenolysis to have glucose for its OWN energy
for what purpose does the liver do glycogenolysis
the liver does glycogenolysis, then ships out the glucose for the rest of the body
What kind of transporter carries glucose in and out of hepatic cells
GLUT-2
is GLUT-2 an insulin dependent transporter
nope
Where do glucose go first after it gets absorbed in the intestines
it goes to the liver
What happens to glucose that is not absorbed in the liver
it goes out to the rest of the tissues
What does the peak in blood glucose cause to happen
secretion of insulin
where does insulin come from
pancreatic beta cells
Which type of cells aren’t insulin dependent
red blood cells white blood cells lens and cornea of the eye liver brain
what is the main function of insulin
causes the absorption of blood glucose into cells
what is the transporter of glucose in the liver
GLUT-2
Which types of cells are insulin dependent
Most tissues, particularly adipose and muscle tissue
Which glucose transmitter is found in muscle and adipose cells
GLUT-4
Which transporter is insulin dependent
GLUT-4
What is the process of glucose uptake in cells that are insulin dependant after a carbohydrate meal
- a spike in blood glucose occurs
- spike in blood glucose causes secretion of insulin
- insulin binds its receptor
- this causes vesicles with GLUT-4 to move to, and fuse with the membrane
- the GLUT 4 now in the membrane transports glucose into the cell
what is the process of glucose uptake in cells that are insulin dependent while fasting
- no spike in blood glucose
- this means no insulin secretion
- vesicles with GLUT-4 move away from the membrane
- less GLUT-4 in the membrane leads to less glucose absorption.
What is PKB and how does it affect the insulin/GLUT-4 process
- insulin activates its receptor
- its receptor sends a substrate of some sort to PKB
- substrate activates PKB
- PKB phosphorylates contractile elements to bring the vesicles with GLUT-4 to the membrane
What is diabetes mellitus
a group of disorders that have absolute or relative deficiencies of insulin
What do all types and disorders of diabetes exhibit
hyperglycemia (high blood sugar)
What is the process by which muscles get glucose while you are fasting
- Muscle contraction uses ATP and gives off ADP and Pi
- 2 ADP’s are used by adenylate kinase to produce ATP and AMP
- ATP is used up in contractions, but AMP levels in the cell rise
- High AMP levels stimulate AMPK
- AMPK causes the translocation of GLUT-4 vesicles to the membrane
What enzyme uses two ADPs to create ATP and AMP
adenylate kinase
what happens in muscle cells when AMP levels get high
AMPK is activated
What does AMPK do in muscles cells
it causes translocation of the GLUT-4 vesicles to the membrane
what is another way for muscle cells to bring the vesicles with GLUT-4 into the membrane besides insulin
muscular contractions (ATP–> ADP–>AMP–>AMPK–>translocation of GLUT-4 vesicles)
What is the first step of glucose metabolism regardless of the path that it will take
Reaction with glucokinase, or hexokinase into
GLUCOSE-6-Phospate
What do kinases do
they phosphorylate things
Why is the phosphorylation of glucose into glucose-6-phosphate so important
- glucose-6-phosphate it highly charged and polar. This makes it so it can’t leave the cell
- changing it from glucose maintains a concentration gradient or high glucose on the outside and low glucose on the inside so that the GLUTs can continue to bring glucose into the cell
Are GLUT transporters active or passive transporters
they are passive meaning that they work with a concentration gradient
What is hexokinase
a phosphorylating enzyme that converts glucose into glucose-6-phosphate.
where is hexokinase found
in all cells, including the liver
what is glucokinase
a phosphorylating enzyme that converts glucose into glucose-6-phosphate.
Where is glucokinase found
only in the liver
What is the Km of hexokinase
.2 mM
What is the Km of glucokinase
10mM
how is the high Km of glucokinase in comparison to the low Km of hexokinase significant
- This means that Hexokinase has a much greater affinity to glucose than Glucokinase.
- It also means that the speed at which hexokinase converts glucose into glucose-6-phosphate will be much less affected by decreases in blood glucose than Glucokinase.
What does the Km of a substance refer to
it refers to the amount of substrate that is needed to have the reaction at half of it’s maximum speed (1/2 Vmax)
What is the normal range for blood glucose concentration
70-100 mg/dL
What is the concentration of blood glucose needed for hexokinase to be at it’s half of it’s maximum reaction speed (1/2 Vmax)
3.6 mg/dL
What does it mean that hexokinase will be at half of its maximum reaction speed when blood glucose is at 3.6 mg/dL
that hexokinase will be completely saturated, even when blood glucose is well below it’s normal range, and an increase in blood glucose won’t cause it to be more saturated.
(even when blood glucose is low or high, hexokinase will still be converting glucose into glucose-6-phosphate at a high rate)
What is the concentration of blood glucose needed for glucokinase to be at its half of maximum reaction speed (1/2 Vmax)
180 mg/dL
what does it mean that glucokinase will be at half of its maximum reaction speed when blood pressure is at 180mg/dL
that glucokinase will be well below saturation at normal blood glucose levels, and that a change in blood glucose levels will highly affect the saturation of, and the speed of reaction of glucokinase.
(when blood glucose is low, glucokinase activity is low. when blood glucose is high, glucokinase activity is high)
What does it mean that hexokinase is a constitutive enzyme
that it is always at optimal levels all of the time
What does it mean that glucokinase is an induced enzyme
that it is only at optimal levels in the presence of the inducer
what is the inducer of glucokinase
insulin
how does insulin induce glucokinase
by phosphorylation
Is hexokinase inhibited by glucose-6-phosphate
yes
is glucokinase inhibited by glucose-6-phosphate
no
In people with type 1 diabetes how would the activity of glucokinase be
it would be low because the synthesis of glucokinase is induced by insulin
When is glucokinase activity high
shortly after a carbohydrate meal
When is glucokinase activity low
between meals/when fasting
when is hexokinase activity high
it’s always constant (except in very severe cases of hypoglycemia)
How active do we want glucokinase while we are fasting
we want it inactive while we are fasting, so that more glucose can be sent out to the body
What keeps glucokinase inactive while we are fasting
glucokinase regulatory protein binds to glucokinase inactivating it
Where is glucokinase located when bound to the glucokinase regulatory protein
in the nucleus
what causes glucokinase to be released from the glucokinase regulatory in the protein
a rise in glucose levels in the cell, due to a rise in blood glucose levels after a meal
What causes glucokinase to be sent back into the nucleus and to be bound and inactivated by glucokinase regualtory protein
an increase in concentration of fructose-6-phosphate in the cell (an intermediate in glycogenesis)
What besides glucose in the cell can cause glucokinase to be released by glucokinase regulatory protein
an increase in concentration of fructose-1-phosphate in the cell (from fructose)
What begins to occur when we are fasting that causes glucokinase to be bound by glucokinase regulatory protein
gluconeogenesis
what about gluconeogenesis causes glucokinase to be bound by glucokinase regulatory protein
in gluconeogenesis, Amino Acids, lactate, glycerol, and pyruvate are converted into fructose-6-phosphate (on their way to becoming glucose) this is what causes glucokinase regulatory protein to bind glucokinase
What affect does insulin have on glucokinase
Insulin induces glucokinase by upregulating the production of it
How does insulin influence the absorption of blood glucose into the liver
it doesn’t directly assist in bringing in glucose. But it does induce glucokinase, which converts glucose into glucose-6-phosphate when it enters the cell. this keeps the glucose concentration low in the cell and the glucose gradient pushes glucose into the cell
Which enzyme would be better for the brain, glucokinase or hexokinase
hexokinase, because it has a higher affinity for glucose and is always active, even in low blood glucose levels. Glucokinase would be bad because it is only active in high blood glucose levels
is someone with defective glucokinase, with low activity, considered diabetic, Why?
Yes, because they would have a decreased ability to phosphorylate Glucose and thus less glucose would enter the liver, and more would stay in the blood
in the final step of glycogenolysis and gluconeogenesis what is the benefit of controlling glucokinase by it binding to GKRP
glycogenolysis and gluconeogenesis are attempting to make glucose, if glucokinase weren’t controlled it would be working in oppposition to these, turning glucose back into glucose-6-phosphate
Which has a higher Km glucokinase, or hexokinase
glucokinase
Is hexokinase or glucokinase inhibited by glucose-6-phosphate
hexokinase
Which tissue uses the GLUT-2 transporter, liver or muscle
liver
which tissue has glucokinase, liver or muscle
liver
What are the steps of glycogenesis
- glucokinase/hexokinase convert glucose into glucose-6-phosphate
- glucose-6-phosphate is isomerized into glucose-1-phosphate by phosphoglucomutase
- glucose-1-phosphate and UTP are combined to form UDP-glucose and PPi
- PPi is hydrolized to form two molecules of inorganic phosphate Pi
- The Glucose end of UDP-glucose is transferred to a glycogen primer at the non-reducing end by glycogen synthase
What is a glycogen primer
it is a protein molecule on the reducing end, with a few glucose molecules bound by alpha 1-4 bonds.
When we use up glycogen in fasting, do we use all of our glycogen that we have stored
no, we leave a little bit as a primer
To which end of a glycogen chain or glycogen primer do we add new glucose molecules (from UDP-glucose via glycogen synthase)
the non-reducing end
What kind of bond is created between the glucoses of glycogen
Alpha 1-4
What happens to the UDP-portion of UDP-glucose after glucose is added to the existing glycogen chain
nucleoside diphosphokinase transfers the terminal phosphoryl from ATP to UDP regenerating the UTP we need to create UDP-Glucose
What happens if there are no glycogen primers upon which to add more molecules of glucose (from UDP glucose)
the protein Glycogenin can serve as an acceptor of the glucose molecules
What is the structure of glycogenin
it is a dimer, in which there are receptor tyrosine residues on each end (head and toe), these tyrosine residues bind a few glucose molecules from UDP glucose, then glycogen synthase adds more to it
what happens to glycogenin after a long glycogen chain has been added
it remains attached to the glycogen strand
is ATP used in glycogenesis
Yes
how many ATPs are used in each round (addition of one glucose) of glycogenesis
2 ATP are used
in which steps of glycogenesis is ATP used
- glucose to glucose-6-phosphate by glucokinase or hexokinase
- UDP to UTP
Is glycogen branched or not
it is branched
What enzyme is used in the branching of glycogen
the branching enzyme (glucosyl 4:6 transferase)
What kind of bond is used between the branches of glycogen
alpha 1-6 bond
How does branching of glycogen happen
the branching enzyme cleaves off 5-8 of the glucoses on the non reducing end of a glycogen strand and transfers it to an interior portion of the glycogen
What type of end does the branching of glycogen create more of? reducing or non reducing
non reducing
why is it significant that many non reducing ends are created in the branching of glycogen
because that means that there are many more non-reducing ends to which more glucose can be attached
How many more non-reducing ends are made per each new branch of glycogen made
1 non-reducing end per branch of glycogen formed
How close can a new branch of glycogen be added to an existing branch point of glycogen
the new branch of glycogen needs to be at least 4 units away from the existing branch point
Why does the cell store glycogen instead of glucose
because glucose is osmotically active and if there were too high of concentrations in the cell, then the cell would lyse (tear/blow up and die)