PPP and Glucuronate Pathway (midterm) Flashcards
What is another name for the pentose phosphate pathway (PPP)?
hexose monophosphate shunt
hexose because its starts with G6P and the shunt will make ribose5P, also known as pentose5P
In most tissues, 80-90% glucose oxidation occurs through glycolysis and the TCA cycle, and the PPP oxidizes the remaining 10-20%. However, glucose flows to the PPP markedly accelerated in fast proliferating tissues and tissues with oxidative stress. What tissues are considered fast proliferating and which ones with oxidative stress?
fast proliferating tissues
-tissues that have high demand for DNA, so stem cells, WBCs, RBCs, macrophages, etc
-tumors
tissues with oxidative stress
-requires NADPH, which is an antioxidant and helps with oxidative stress
-RBCs have a lot of oxidative stress because they carry lots of oxygen
note: most cells in body are not fast proliferating, ex: neurons
Does PPP require oxygen?
no, its anaerobic
Does PPP require energy?
no, no ATP is consumed or generated in this pathway
Where does PPP occur?
in the cytoplasm (bc RBCs don’t have mitochondria)
What are the important products of the PPP?
NADPH, ribose 5 phosphate (creates DNA/RNA, also known as pentose 5 phosphate), and other sugars
What is the RLE in PPP?
glucose 6 phosphate DH
In PPP, glucose converts to G6P with GK or HK. G6P then converts to phosphogluconolactone with NADP+ and what enzyme?
G6P DH (this is the RLE in PPP)
In PPP, glucose converts to G6P with GK or HK. G6P then converts to phosphogluconolactone with NADP+ and G6P DH. Phosphogluconolactone then converts to 6 phosphogluconate with what enzyme?
lactonase
In PPP, glucose converts to G6P with GK or HK. G6P then converts to phosphogluconolactone with NADP+ and G6P DH. Phosphogluconolactone then converts to 6 phosphogluconate with lactonase. 6 phosphogluconate then converts to ribulose 5 phosphate with NADP+ and what enzyme?
6 phosphogluconate DH (also co2 will be released in process)
In PPP, glucose converts to G6P with GK or HK. G6P then converts to phosphogluconolactone with NADP+ and G6P DH. Phosphogluconolactone then converts to 6 phosphogluconate with lactonase. 6 phosphogluconate then converts to ribulose 5 phosphate with NADP+ and 6 phosphogluconate DH (also carbon dioxide will be released in process). At this point ribulose 5 phosphate has 2 options. One option is to convert to ribose 5 phosphate with what enzyme?
phosphopentose isomerase
Is ribulose an aldose or a ketose?
ketose
Is ribose an aldose or a ketose?
aldose
In PPP, glucose converts to G6P with GK or HK. G6P then converts to phosphogluconolactone with NADP+ and G6P DH. Phosphogluconolactone then converts to 6 phosphogluconate with lactonase. 6 phosphogluconate then converts to ribulose 5 phosphate with NADP+ and 6 phosphogluconate DH (also carbon dioxide will be released in process). At this point ribulose 5 phosphate has 2 options. One option is to convert to a sugar product like F6P or GAP with what enzyme?
transketolase (note ribose 5 phosphate can also use this enzyme to change into a sugar product)
What 2 enzymes in PPP pathway make NADPH?
G6P DH and 6 phosphogluconate DH
What is G6P DH (also known as G6PD) deficiency?
-x linked recessive disease, so more common in males
-NADPH levels are low (evident in RBCs)
-NADPH is an antioxidant and is needed to convert H2O2 to water
-ROS increase in RBCs which causes hemolysis and is especially triggered with infections and drugs
-results in acute anemia and bloody urine
The glucuronate pathway is important for producing….
1) UDP glucuronate (also known as UDP glucuronic acid)
2) L ascorbic acid (vitamin C- this is essential, if you don’t have enough then you can get scurvy) in some animals BUT NOT HUMANS
What are proteoglycans?
long chains of glycoaminoglycans (GAGs) attached to a core protein, usually contains glucuronic acids (jelly like)
What is hyaluronate?
a GAG with a repeating disaccharide
T/F: Glucuronate synthesizes GAGs
true
What are the 3 types of GAGs we went over in class?
1) hyaluronate
2) chondrotin sulfate
3) heparin
UDP glucuronate is negatively charged. Why is this beneficial?
most bad things in the body like cancer or toxins are positively charged, so this allows for easy binding and allows UDP glucuronate to get rid of it
What are the MANY functions of UDP glucuronate?
1) makes heteropolysacchardies and proteoglycans
2) precursor for l-ascorbic acid and vit C synthesis in animals (not humans)
3) detoxification from antibiotics, pesticides, carcinogens, etc.
4) makes UDP xylose (its the first sugar that proteins bind to)
5) steroid hormone excretion (get rid of excess estrogen so it prevents breast cancer)
6) bilirubin metabolism
Where is bilirubin synthesized from?
heme
Heme is a prosthetic group of….
hemoglobin
How long do RBCs survive?
3-5 months
What happens at the end of the lifespan for RBCs?
they go to spleen to be broken down and heme will be converted to bilirubin to be excreted
heme in this process can also secrete biliverdin to be excreted
In the liver, bilirubin will bind to glucuronate. What is this called?
test q
conjugated or direct bilirubin (no glucuronate= indirect bilirubin)
direct bilirubin allows bile to be secreted for excretion when person has high fat diet
What is physiological jaundice?
-jaundice with newborn
-indirect bilirubin jaundice
-babies have increased bilirubin levels in blood because they have Hbf and once the RBCs are at the end of their lifespan they need to be broken down and new RBCs will be replaced with “adult Hb” and this will result in high hemolysis
-newborns have a glucuronate deficiency
-tx: put baby in blue light
What is jaundice in adults caused by?
-hepatic damage usually after infection
-direct bilirubin jaundice
-severe cases= liver functions are compromised and then can also be indirect jaundice
What jaundice is caused by bile duct obstructions?
-bile duct is blocked by tumor, gallstone, etc
-liver function is usually fine and can still make direct bilirubin but it cannot release bile which becomes problematic
-results in direct bilirubin jaundice
-bile cannot be excreted so the pt will have light color or clay colored stools
