Flashcards in 9/25 Metabolism! Deck (62):
every cell in the body can perform this all important biochemical reaction:
why would someone be considered diabetic if the glucose level is higher than 120mg/dL?
becasue normal is 70-100mg/dL
Not all foods give us glucose... what other carb monomers can we utilize?
galactose from milk's lactose, and fructose!
with out the liver, it would be difficult to live...but also to eat fruit! why?!
the liver digests fructose!
milk can be metabolized by some cells, but not directly first it must become this other monomer:
the most sugar happy organ of the body...
the brain! using 130g/day!
The brain wouldn't mind a fat free diet...
it can't metabolized fatty acids for energy
removal of the mitochondria from a cell (RBC, i'm talking to you!) makes a cell completely dependent antother energy source....
Glycolysis and the ATP that it produces!
I just ate a killer icecream sundae! what organ and what cell and what hormone is going to freak out?!
Pancreaus, beta cells, insulin will!
why is insulin so dang popular in the body; how can it affect so much?!
insulin receptors are on most cells of the body, and signals them to increase usage of nutrients and grow and store energy! -- it is a potent anabolic hormone
The anti-particle to insulin?
Glucagon, Where does it come from, and why is it secreted?
from alpha cells of the islet cells in the pancreus, in response to low blood sugar
what does the Glucagon do?
it signals in the liver and adipose, leads to the release glucose and prevent hypoglycemia.
how would an absence of this transporter lead to much slower insulin responses to rising blood sugar levels?
GLUT 2 is the glucose transporter in the pancreatic islet cells and the hepatocytes, it is low affinity high capacity transporter.
why would the hepatic cells need GLUT 2 receptors -- they don't need to release insulin!
they take up a lot of the extra glucose and store it as glycogen, and some as triacylglycerol.
compare the GLUT 1, GLUT 2, GLUT 4 transporters
GLUT1 : Membrane: moderate level of glucose enter the cell. (most cells)
GLUT 2: Membrane: Pancreus/Liver: Low afinity, High capacity.
GLUT 4: Cycles between the Membrane and Vesicles: Striated Muscle/Adipose: Insulin/exercise activated (exercise activated in muscle only)!!
this transporter related mechanism is the most important means of maintaining blood glucose levels as constant
GLUT 4 binding and unbinding the plasma membrane in skeletal and cardiac muscle and adipose tissue
Glycolysis (that reaction series that we love to hate) summerize it!
Ten reactions that occur in the cytosol of all of our cells. result in converting the 6 carbon glucose into two 3 carbon pyruvate molecules. Also a net produciton of two ATP and two NAD are reduced to NADH
Ahhhh! 10 reactions in Glycolysis, how can we simplify this into groups of reactions?!
3 general stages:
1. trapping and destabilization.
3. Oxidation and ATP generation
what is the 1. trapping and destabilization sate of glycolysis?
Phosphorylation of glucose traps it in the cell.
Isomeration to fructose and a second phosphorylation leads to a destabilized molecule. This is of course accomplished by Kinases
The second phase of glycolysis is cleavage...talk a little about that
the 6 carbon mlecule is cleaved into two interconvertible 3-carbon molecules by aldolase! the result is glyceraldehyde 3-phosphate (X2)
the third phase of glycolysis is Oxidation and ATP generation...discuss this a little
Six reactions that yield 4 ATP and 2 NADH (we used 2 ATP to get here though!)
Overall we oxidize glyceraldehyde 3 phosphate into pyruvate. The final reaction is with pyruvate kinase (though it is really taking phosphate from pyruvate and putting it on ADP)
Glycolysis...so important...how do we regulate it
through the availability of glucose using GLUT 4 movement; or through reg. the breakdown of glycogen. Also through its committed step.
What is the commited step in Glycolysis?
The phosphorylation of fructose 6 phosphate to fructose 1,6 bisphosphate! (this is only useful for glycolysis!!)
What enzyme will cause the commited step of glycolysis to take place?
How do I get phosphofructokinase up off the couch and activated?!
Elevated levels of AMP will allosterically activate it! or activated by a sice product of glycolysis, fructose 2,6 bisphosphate.
What kind of difficiency would lead to a disconnect between glycolysis and the TCA cycle?
the loss of the ability to oxidatively decarboxylate pyruvate in the mitochondria by the complex pyruvate dehydrogenase
What co-factor deficiency would lead to an inability to get the product of glycolysis into the TCA cycle?
What are the possible uses of the product of pyruvate dehydrogenase?
The product is acetyl CoA as made from pyruvate. This can be used in the TCA cycle. In liver and adipose it can by used to make fatty acid and triacylglycerol. Or it can by used for cholesterol synthesis.
Hmmm 2 ATP from glycolysis...not that impressive...what else you got?!
The two NADH produced go to the mitochondria and add to the proton gradient, the pyruvate go to the TCA cycle and add to the NADH/FADH that add to the proton gradient and ultimately give 30 to 40 total ATP for complete oxydation of glucose!
while exercising really hard, the oxygen levels in the cell go down...now what happens to pyruvate?
It is reduced to lactate, by oxidizing NADH back to NAD+ . This is done by the enzyme lactate dehydrogenase
Wow, I'm really exercising...why is my blood pH decreasing?!
Lactate is co transported with a proton out of the cells where it was made and into the blood stream! This can lead to lactic acidosis!
how can I get rid of the extra lactate in my blood stream?
by absorbing the lactate in to cells that have enough oxygen and NADH to drive the lactate dehydrogenase reaction in the other direction (it is reversible)
Why might the eyes be so sensitive to glucose levels?
there is no mitochondria in the lens of the eye, therefore they only do the anerobic catabolism of glucose through the glycolysis mech. and then release lactate constantly
Why can't red blood cells or the lens of the eye use fatty acids or amino acids as sources of energy
they lack mitochondria, which is necessary to catabolize these molecules in the TCA cycle.
Why do lactate levels in the blood not really rise that much during exercise
The fast twitch fibers do rely on anerobic catabolism a lot and give off lactate, but the liver will absorb this lactate and convert it back to glucose.
there is a disterbence in oxygen delivery and mitochondria function in the liver, why would the blood pH go down?
Lactic Acidosis where the extra lactate production and subsequent transport out of the cells with a proton results in such high lactate levels that the buffers in the blood are overwellmed and pH drops below 7.2
Not all of the glucose that enters the cell will eventually go to glycolysis where else could it end up?
the Pentose phosphate pathway
what is the product of the pentose phosphate pathway
1. NADPH from NADP+ and
2. 5 carbon sugar ribose 5-phosphate.
Where does the Pentose phosphate pathway occur?
In the cytosol of the cell.
What are the purposes of the products of the pentose phosphate pathway?
Ribose sugar to make nucleotides, and NADPH for anabolic reactions and to detoxify!
How can NADPH act as a detoxification molecule?
It acts to re-reduce glutathione that has become oxidized through protecting our cells form oxidative damage. Many such ezymes are expressed in the liver!
why would we have a lot of NADPH (reduced form) but not a lot of NADH (reduced form) in the cells at any given time
NADH is used to make energy and is used quickly, while we maintain a resevior of its substrate, NADPH is used to detoxify and we maintain a resivour of it.
How do we launch the Pentose phosphate pathway?
when NADPH levels in the cell drop then more glucose 6-phosphate will interact with the enzyme Glucose 6-phosphate dehydrogenase (G6PD)
What does G6PD do?
Glucose 6 Phosphate Dehydrogenase catalyzes the oxidation of glucose 6 phosphat, while simultaneusouly reducing NADP+ to NADPH.
How is G6PD controlled
Glucose 6 phosphate dehydrogenase is inhibited by NADPH!
After the creation of NADPH what happens to the rest of the carbons that came from the glucose through G6PD?
they can go back into glycolysis or they can go to make ribose!
What if I have a defect in G6PD?
then you would be amoung the most common genetic enzyme deficiency, you would have greatest effect on RBC that have no other way to make NADPH, and could lead to hemolytic anemia. this is usually not the case unless other stressers are present.
Why do more men have G6PD deficiency?
It is x-linked.
What types of things could lead to hemolytic anemia if there is a difficincy in G6PD?
oxidant drugs (antimalarials) Fava beans, or severe infections
Glucose is the king of metabolism: how is it stored and how can the liver and sometimes the kidney cortex help supply more of it
most cells store it as glycogen. The liver and sometimes the kidney cortex synthesize glucose from amino acids, lactate and glycerol.
Glucose is king, what are the other two 6-carbon dietary sugars?
Fructose and galactose.
What is the first step in the catabolism of any sugar?
Phosphorilation to trap it in the cell
Why is fructose only catabolized in the liver?
only the aldolase that is found in the liver is able to slowly catalyze the split of fructose that has only been phosphorylated once.
Why would some children die from eating apple sauce?
They have hereditary fructose intolerance where they don't have the liver form of aldase, and can't break down fructose and so the liver is damaged.
Why would fructose (fruit sugar) ever be bad for us if it is from plants?
because in very high amounts found in the artificial sweetners it can lead to excess fatty acid and triacyglycerol synthesis and abdominal obesity.
What is the fate of galactose
it parrallels glucose. It is taken up by most cells through GLUT transporter and then phophorlylated, then galactose 1-phosphate uridyltransferase adds UDP and that product can then go to glucose and enter glycolysis.
what is classical glactosemia
defect in galactose 1-phosphate uridylltransferase: galactose 1-P acumulates and is elevated in blood and urine. The result is cataracts in the eyes, mental retardation, and death from liver damage.
what are the essential dietary constiuents
the body can make carbs from other things, so these are not essential. there are essential amino acids and fatty acids that we cannot make and must eat.
what sugar based marker can be used to detect cancer
FDG uptake (a radiopharmaceutical) that is taken up in glucose transporters. Malignant cells have many more glucose transporters, more hexokinase action, and diminished phosphatase activity.
in RBC 2,3 BPG is made in a side path off of glycolysis. Why would this be good during exercise?
2,3 bisphosphoglycerate stabilizes a form of hemoglobin that has a lower affinity for oxygen, therefore increases the release of oxygen to tissue.