Lecture5-PENTOSE PHOSPHATE PATHWAY Flashcards
what is the significance or function of Pentose phosphate pathway?
-Production of ribose (pentose) sugars for DNA and RNA biosynthesis
-Production of NADPH for an essential reducing equivalent for biosynthesis of fatty acids and sterols (cholesterol, hormones), and for maintenance of reduced glutathione (red blood cells).
What is the net energy produced for PPP?
2 NADPH
What is the rate limiting enzyme for PPP?
Glucose -6- phosphate dehydrogenase
What is the phase 1 of PPP? oxidative or non oxidative and give me the details of it
-Oxidative
What is the phase 2 of PPP? oxidative or non oxidative and give me the details of it
Non-oxidative
when is NADPH produced in PPP? what enzyme?
phase one–> oxidative phase
Glucose -6- phosphate dehydrogenase
6-phosphogluconate dehydrogenase
Glyceraldehyde 3-phosphate from PPP can be linked to?
Glycolysis
Ribose 5 phosphate is used for what?
ribose suger in DNA and RNA
The enzyme transketolase is what PPP phase and what is unique about it?
Phase 2: non oxidative phase
Needs thiamine and vitamin b1 to function
What is the phase 2 of PPP? oxidative or non oxidative and give me the details of it
Non-oxidative
What is fructose 6 phosphate linked to and where is it produced?
glycolysis and phase 2
There are two molecules that link to other pathways produced in the PPP, what are they and what pathways
Glyceraldehyde 6 phosphate and fructose 6-phosphate
glycolysis
The production of NADPH in PPP is used for what?
oxidative stress protection, fatty acid and sterol synthesis
There are how many modes for the production of ribose 5 phosphate, NADPH or ATP?
4 modes
What is mode 1 product(s) and what is it for?
-produces ribose 5 phosphate
- good for DNA replication
What is mode 2 product(s) and what is it for?
Produces 2 NADPH and ribose 5 phosphate
- good for tumor cells to protect against ROS
What is mode 3 product(s) and what is it for?
-Produces 2 NADPH, glyceraldehyde 3 phosphate and dihydroxyacetone phosphate
- Good for ros protection and no ribose 5- phosphate–> RBC
EXTRA
-glyceraldehyde 3 phosphate and dihydroxyacetone phosphate used for glycolysis
- NADPH used for ros protection
- no ribose 5- phosphate
What is mode 4 product(s) and what is it for?
-produces 2NADPH, 2ATP and pyruvate for glycolysis
- good for normal cell and ATP production
What is Glutathione?
-a tripeptide (glutamate, cysteine and glycine) for protection of cells from oxidative stress
-EX: mitochondria and RBC
How does glutathione protect against oxidative stress?
a) Scavenging of peroxide by glutathione peroxidase and
b) regeneration of reduced glutathione by glutathione reductase using NADPH as the reducing agent
What does selenium functions as?
functions as a necessary component of enzymes involved in antioxidant protection ( glutathione peroxidase and thioredoxin reductase) and thyroid hormone metabolism
Does selenium react faster or slower with ROSs compared to sulfur in cysteine?
faster
Why is selenium faster at reacting with ROSs?
The reason for this is that the outer valence electrons of selenium are more loosely held than those of sulfur. As a result, selenium is a better nucleophile and will react with reactive oxygen species faster than sulfur
EXTRA:
But, the resulting lack of π-bond character in the Se-O bond means that the Se-oxide can be much more readily reduced in comparison to S-oxides.
What are enzyme is linked diseases linked to PPP? what are the diseases?
Glucose-6-phosphate dehydrogenase deficiency–> hemolytic anemia, jaundice and tumors
Glucose-6-phosphate dehydrogenase deficiency causes what?
Hemolytic anemia and jaundice in the sclera
Glucose-6-phosphate dehydrogenase deficiency–> genetics?
X-linked recessive hereditary
A kid as a Glucose-6-phosphate dehydrogenase deficiency and eats lava beans, what happens? side effects?
jaundice in the sclera
Increased chemical and drug sensitivity particularly in children with G6PD deficiencies (e.g. against sulfonamides, aspirin, some antimalarial drugs).
Glucose-6-phosphate dehydrogenase deficiency protects against what?
malaria
What drives DNA synthesis in Tumor cells?
Glycolysis
In tumor cells what is blocked in the glycolysis?
Blocked at the pyruvate kinase step
What happens when the pyruvate kinase step is blocked in glycolysis?
Glycolysis intermediates are diverted into pentose-phosphate pathway to form ribose sugars for increased DNA synthesis
What is the Warburg effect?
Increases glycolysis with minimal ATP/energy production
In tumor cells, PPP is driving what?
increased NADPH production to protect against ROS
What is associated with rapidly proliferating tumor cells?
Formation of NADPH as protection against ROS
what is “hallmarks” of tumor metabolism? (this one is hard, so you can look at slides instead of answering)
Increase GLUT1 –> increase glucose uptake (Warburg effect), increase gluconeogenesis of liver
Tumor express embryonic M2-PK pyruvate kinase (lower substrate affinity
Pyruvate kinase is blocked and g-6-p is shifted to PPP for ribose sugars and NADPH
tumors secret lactate which increases LDH—> breakdown of glutamine and alanine to pyruvate as an alt. energy source of TCA cycle resulting in weight loss
What causing weight lost in cancer patients
tumors secret lactate which increases LDH—> breakdown of glutamine and alanine to pyruvate as an alt. energy source of TCA cycle resulting in weight loss
what are the sources of dietary fructose?
Sucrose-containing foods and beverages
non diet soft drinks (high fructose corn syrup)
What happens when fructose enters the liver/ glycolysis?
The phosphofructokinase (RLS) os normal glycolysis is bypassed and goes to F-1-P plus producing ATP.
What does aldolase B do?
Fructose 1-p –> Glyceraldehyde + Dihydroxyacetone
Glyceraldehyde–> glycolysis
A build up of F-1-P can cause what?
mental retardation
What is hereditary fructose intolerance?
-Fructose 1-p cannot go to Glyceraldehyde + Dihydroxyacetone phosphate
- inhibits glycogen phosphorylase (glycogen breakdown)
- results in fructose-induced hypoglycemia
What is the treatment of Hereditary Fructose Intolerance ?
-Treatment: limit ingestion of fruits, table sugar, and other sweets
What is the major source of galactose in human diets?
lactose –> milk and milk products
Lactose can or cannot be absorbed in the intestine? what is the process?
cannot so it needs to be cleaved by lactase enzyme into lactose and glucose
What does lactose get cleaved into ?
galactose and glucose
what is causes non classical galactosemia?
-caused by galactokinase deficiency
what does non classical galactosemia lead to and how?
Cataracts
- No galactokinase so a build up of galactose which gets turned to galactitol by aldose reductase
What causes classical galactosemia ?
galactose 1-P accumulates in tissues and galactose so increase of galactose
what does classical galactosemia led to and how?
cataracts and irreversible mental retardation
no Galactose-1-P uridyltransferase so build up of galactose-1-p so increase galactose
how is lactose synthesized?
besides galactitol, what else can cause cataracts?
chronically elevated blood glucose levels in poorly controlled diabetes
How do poorly controlled diabetes get cataracts?
sorbitol levels increase in the lens of the eye, and can lead to cataract formation.
What is galactosemia?
is an impairment of galactose metabolism caused by abnormal liver function
what is the most common initial clinical symptom of galactosemia?
failure to thrive
In galactosemia what happens when milk is ingested?
Vomiting or diarrhea
jaundice in some
Galactosemia causes what within a few days of birth
cataracts
What is the treatment of Galactosemia?
-strictly avoiding all milk and milk-containing products.
- The infant can be fed with soy formula, meat-base formula, or Nutramigen (a protein hydrolysate formula)
- condition is lifelong
