Where is the hexomonophosphate shunt/PPP located
In the CYTSOL of liver, mammary glands, skin, adipocytes, and RBC
What does the PPP produce
NADPH- needed for fat synthesis and to protect agaisnt free radicals
Converts Hexoses into pentoses (ribose 5-P) that are needed for DNA and RNA synthesis
Also interconverts C3, C4, C6 and C7 sugars for further use or to redirect them to the glycolysis pathway.
Phase 1 of oxido reudction and NADPH production
Glucose 6-P--- glucose6- phophatase dehydrogenase--> NADPH + Ribose 5-P (only regulatory step inhibited by NADPH and inhibited in liver by fatty actyl-CoA)
What produces the second NADPH in the PPP
6-Phosphogluconate dehydrogenase (this is a dehydorgenation and decarboxylation)
6-phosphogluconate ribulose---6-Phosphogluconate dehydrogenase---> 5-P
This is the step when you start with a 6 carbon and end with a 5 carbon sugar.
Uses of NADPH
1. Reductive biosynthesis: fatty acids synthesis, steroid synthesis
2. Fighting against reactive oxygen species: glutathione system
3. Cytochrome P450 monooxygenase system: steroid synthesis, vitamin D activation,
4. Phagocytosis by white blood cells
5. Synthesis of nitric oxide (NO) – relaxes smooth muscle; prevents platelet aggregation;
mediates tumoricidal and bacteriocidal actions of macrophages
Why is RBC usage of glucose so high compared to other cells?
What's hte use of the NAPDH form? Deficiency?
Tht's the only source of energy but also because the PPP shunt uses glucose to make NADPH to protect the RBC membrance from oxidative damage
Glucose 5-phosphate makes NADPH which is used in the Glucthionne system which is a tri-peptide with an active SH group. A single gluthione can oxidize and form an S-S bridge the NADPH is used to reduce the glucathione back which is use to get rid of H2O2
there is a genetic defect that doesn't allow the production of NADPH because there is no Glucose 6-phosphate so the RBC lyse
Whats the purpose of the 2nd phase of PPP
Interconverts the different carbon sugars and gives the cell a chance to take out whatever it may need; if nothing then these steps will be used to convert steps of phase 1 to glycotisis
The phase 2 of PPP does interconversion between carbons. Name key enzymes and what they do
Transketolase (requires TPP/B1 vitamin and Mg2+)- transfers C2 unit making a 7 and 3carbon group
transaldolase- transfers a C3 to from a sugar making a 4 and 6 carbon unit (this step is after the transketolase)
We want to end with chain that could enter glycolysis so Glyceraldehyde 3-phosphate and fructose 6-phosphate
Process of PPP when you only need NADPH
You don't want to lose carbons so you want to use allcarbons and taking NADPH each time. So we use Glyceraldehyde 3-phophsate and fructose 6-phosphate and feed them back into the Glucose 6-phophate taking out 2 NADPH each time getting a total of 12
What's the 3rd outcome for the shunt?
We use the PPP for nucloetide synthesis. So here we use the glyceraldehyde 3-P and the fructose 6-P and convert them 3 ribose 5-P by reversing the transalsolase and transketoase
Tissues that use PPP and why?
RBC- need NADPH to reduce gluthione that fight the oxidative attack on the membrane
Liver, mammary gland, testis, adrenal cortex- NADPH for fatty acid and steriod synthesis
Liver- NADPH for cytohrome P450 system in detex
Striated muscle has NO PPP
Frcutose convertsion to glcuose- steps
The fructose is phosphoylated by frcutokinase and becomes F-1-P which is spilt by aldolase into 3 caborn sugars. It makes DHAP and Glyceraldyde(not phosphorylated) so it is reduced to glycerol which is phophorylated. So we end up with two DHAP going into glycolysis
What is the disorder when fructokinase is missing
Essential fructosuria. JUst means we eat frcutose but can't use it. So we excrete it in our urine
Deficiency of Aldolase B results in?
Herediary frcutose intolerance and causes the accumulation of the Frcutose 1-P wasting the tied up pshophate so there isn't enough phosphate for terminal energy.
Causes hypoglycemia- accumulating the frcutose 1-P upreglating of glucokinase which then it forces glycolsis to run (even when no need) which also sstops glycogen degradation and gluconeogenosis. vomitting, renal dysfunction. Depelete inorganic phosphate (tied up with the frcutose 1-P so no ATP and oxidative phosphoylatoin).
Therapy is to remove glucose and frcutose from the diet.
CAacity of liver of phosphorylation of frcutose vs spiltting of fructose 1-P. What does this mean?
LIver has much greater capacity to phosphoylate fructose than it does to spilts. This means fructose is poorly controlled and excessive frcutose could deplete the liver of ATP and Pi.
What is the polyol pathway
Pathway that makes fructose from glucose used by seminal vesicles (Sperm), lens, kidneys
Makes sorbitol (which is the alcohol) by product. hard to get rid so the reversal is difficult and sorbitol brings in water. NOrmal pathway but with too much glucose causes too much sorbitol and can lead to cell death
Convesin of galactose to glucose
Galactose + ATP --> galactose 1-P + ADP
galactose 1-P uridyl transferase
UDP-glucose + galactose 1-P --> UDP-galactose + glucose 1
What happens when there is a galactokinase deficeincy
Elevation of galatose can make galactol (which acts just like sobitol). Causes eleveated galactose in blood and in urine
What happens when there is a galtdeficiency
Galactose 1-phosphate (GALT) is what activates galactose making it into UDP-galactose. Causing increase in galactose in urine and blood.
Accumulation of galactose 1-P causes lens, nerve and kidney tissue damage
Have to avoid galactose
Functions of gluconronic Acid
1. Glucuronic acid is a precursor in complex carbohydrate synthesis (glycosaminoglycanpolysaccharides) like sulfate, chondrate.
2. Glucuronic acid is crucial in modification of certain drugs and bilirubin to help their excretion. tTe drug or bilirubin (apolar byproduct of heme difficult to excrete) bind to UDP- gluconric acid before excretion.
3. Glucuronic acid is also a precursor of L-ascorbic acid although Humans, other primates and
guinea pig lack the enzyme that converts L-gulonolactone to L-ascorbic acid and thus ascorbic acid must be ingested as vitamin C.
How is gluconornic acid synthesized
From glucose through the activation of glucose to UDP glucoseand reducing UDO-glucose dehydrogenase. Makes NADH in the liver cytosol which is shuttled to the mitochondria.