L10 - Carbohydrates and Glycobiology Flashcards
Glc-6-P pathways
Pentose phosphate pathway (PPP)
Pentose phosphate pathway:
It has a non linear pathway, it has 2 phases.
1)Generates NADPH from Glc6P (oxidative phase)
Glc6P dehydrogenase oxidises NADP > NADPH.
Can be further oxidised to cleave a carbon. 2 NADPH is produced in total. affinity of enzyme for NADP is 1000x more than NAD. Product is ribulose 5 phosphate. Can undergo isomerisation to form a ketose or aldose.
2)Reacts with C3,4,5,6,7 sugars. (non-oxidative)
Uses all Cx sugars to form C5 sugars > synthesis of RNA,
DNA, ATP, NADH, FAD,CoA
Transketolase in PPP: can transfer C2.
Transaldolase: transfer C3 units.
PPP regulation
Mainly influenced by NADPH/NADP.
High NAPDH: mechanism which requires NADPH is stopped. vice versa.
Oxidised and reduced form compete for binding site.
Modes
1: Rapidly dividing cells where R5P is much more required than NADPH.
2: Need for R5P and NADPH is balanced. Glc6P is converted into R5P
3: Need redox power (adipose tissues). More NADPH is required than R5P.
Need Glc-6-P
4: Need NADPH and ATP required. Glc6P and F6P.
Mainly produces Pyruvate.
G6PDH (Zwf)
deficiency protects against falciparum malaria.
Wernicke-Korsakoff Syndrome
transketolase deficiency.
Gylcogen (muscle)
Fuel for ATP production.
Glycogenesis in muscle important for lowering blood glucose
Most of Glc from glycogen consumed without formation of free glucose.
Small ammount of free glucose is immediately consumed in muscle.
Muscle glycogen not important for maintaining blood glucose levels during fasting.
Glycogen (liver)
made from glucose in liver
Main role: maintain blood glucose levels and excretion into the bloodstream.
After a meal, glycogen conc. highest, decrease slowly to maintain blood-glucose levels
Glycogen metabolism
Gylcogenolysis:
1) Release of G1P from glycogen
2) Remodeling of glycogen
3) Conversion of G1P to G6P
Glycogenesis:
1) Glucose activation to UDP-Glc
2) UDP-Glc added to non reducing end of growing glycogen chain
3) Remodeling of glycogen chain
Breakdown begins at the reducing end.
Phosphorylase breaks down at the linear end
Transferase transfer a branch into the linear end and liberatated as Glc.
Glucosidase adds a new branch
Glycogenolysis
Phosphorolysis of glycogen:
catalysed by glycogen phosphorylase
takes a sugar from non-reducing end by using a Pi
Sequential removal up to 4 residues from branch point
Reaction differs from alpha amylase, which uses water, not Pi to cleave bond.
Glycogen remodelling
Debranching enzyme:
removal of branch residues. cleave and transfered to another branch.
tri-glucose unit is cleaved and transfered to non-reducing glucose of a nearby chain.
Glc1P to Glc6P
Catalysed by a mutase, phosphoglucomutase
Ser-phosphorylated enzyme starting point
Enzyme donates its P-group to Glc1P yielding Glc16P and desphorylated .
Original P group of substrate transferred back to enzyme yielding Glc6P and regenerated phosphoenzyme
Glc6P enters metabolic pathway.
(Glucose)n = Glycogen
Net reactions
Liver:
(Glc)n + H20 > (Glc)n-1 + Glc
Muscle:
(Glc)n + 3ADP + 3Pi + H
Diseases in deficiency of glycogen breakdown/synthesis (GSD)
Most affected tissue is liver
Heart and muscle glycogen metabolism defects
Most common GSD is type I, Von Gierke disease, deficiency in G6P phosphatase or G6P transporter in liver,intestinal mucosa, kidney.
Type II or Pompe Disease, linked to cellular processes (eukaryote). Glycogen is broken down in cytosol by lysosome. Pompe occurs when gylcogen does not brekadown inside the lysosome, and builds up. Resulting in cell distortion.
Glycogen synthesis is not the reciprocal of glycogen breakdown
.
Glycogenesis
Net:
Glcn + Glc + 2ATP + H20 > Glcn+1 + 2ADP + 2 Pi + 2H+
