carbohydrate metabolism cont Flashcards
what is the pentose phosphate pathway
*source of nucleotides within cell, has 2 phases
-somewhat anabolic pathway, making mol larger
Oxidative
- oxidation of glucose 6-P → produces 2 NADPH and ribulose 5- phosphate (=> ribose-5-phosphate)
- NAD used as oxidizer
Non-oxidative: isomerization/rearrangements
- glycolytic intermediates
- glucose 6-phosphate
- xylulose 5-phosphate (modulator of phosphatase that stimulates liver PFK-2)
what are the produces of the oxidative phase
→ for the synthesis of nucleotides (ribose 5-phosphate)
→ reductive biosynthesis (NADPH), for e.g. fatty acids
what are the products of the non oxidative phase
→ replenish glucose 6-phosphate and glycolytic intermediates
→ source of xylulose 5-phosphate.
explain non oxidative phase
- start with rubose 5 phos to go to glucose 6 phos
- why? part of this pathway is generating fatty acids adn the other is generating nucleotides
- if need for DNA RNA is low, take the ribulose 5 phosphate and reshuffles it to go back to glucose 6 phosphate (dont want it to build up)
*dont memroize intermediates and all enzymes,
- esentially going from 5 carbon molecule to 6 carbon molecule
what do the diff intermediates and enzymes do in non oxidative phae
Transaldolase/transketolase can transfer 2/3 carbon atoms between sugar phosphates
This allows you to rearrange 5C molecules into 6C molecules
The final 3C sugars are glyceraldehyde-3P, which can turned into glucose-6P by gluconeogensis steps
Net: 6 x 5C –> 5 x 6C
*no ent gain or los of energy, point is to recycle the ribuclose 5 phosphate
how do you regualte the pentose phosphate pathway
Glucose 6-phosphate dehydrogenase is:
- stimulated by NADP+
- inhibited by NADPH
*regulated by redox state of the cytosol
- glucose 6 phos is largly commited to glycolysis to generate ATP
what is glycogen
polymer of glucose (storage)
- quick source of energy
- in the liver we have glycolysis and control of blood [glucose]
mucle: glycolysis
explain glycogen synthesis
Glycogen Synthesis – making the precursor:
- glucose 6-P –> glucose 1-P: Phosphoglucomutase
- glucose 1-P + UTP —> UDP-glucose + PPi: UDP-glucose pyrophosphorylase
UDP-glucose then acts as an activated sugar donor
*by making glycogen we are polymerizing glucose mol and utilizing UDP to do that, glycogen synthase is the enzyme sticking sugar on the growing chain, spitting out UDP
*net result is get a new non reducing end, elongated chain
what is glycogenolysis
- glycogen breakdown
*glycogen phosphorylase reaction
**RECALL: glycogen synthase is inhibited by phosphorylation (PKA and GSK3)
how is glycogen metabolism regulated
- Recall: Glycogen synthase is inhibited by phosphorylation, and glycogen phosphorylase is activated by phosphorylation
what is the role of Glycogen phosphorylase b kinase
Role in glycogen metabolism
- phosphorylates glycogen phosphorylase
- activates glycogen phosphorylase
***The activity of glycogen phosphorylase b kinase is stimulated by PKA-mediated phosphorylation
What is the role of glycogen phosphorylase a phosphatase
- dephosphorylates glycogen phosphorylase
- inhibits glycogen phosphorylase
Glycogen phosphorylase is activated by
phosphorlyation
wht is role of phosphorylase B kinase
phosphorylates glycogen phosphorylase
activates glycogen phosphorylase
The activity of glycogen phosphorylase b kinase is stimulated by PKA-mediated phosphorylation
what is the role of Glycogen phosphorylase a phosphatase
- dephosphorylates glycogen phosphorylase
- inhibits glycogen phosphorylase
what is the role of glycogen phosphorylase
- glucose sensor
- Glucose binding of phosphorylase a has an allosteric effect
- This favours dephosphorylation (and inactivation) by phosphorylase a phosphatase
- allosteric sites are empty when glucose is low, phosphorylated amino acids are tucked away so cant be dephosphorylated
- when glucose levels are high, binding to allosteric sites, conformational change, phosphate groups are exposed and available to be chewed off
*insulin inc activity of phosphatase (makes it less active)
- glucose favours dephosphorylation by making sites availabile to phosphorylase a
how do glycogen synthase and phosphorylase relate
- reciprocally regulated by phosphorylation
- phosphorylation of gly syn a inactivates glycogen synthase b
- glycogen phosphorylase b is phosphorylated becoming active glycogen phosphorylase a
*protein phosphatase dephosphorylases both glycogen synthase b and glycogen phosphorylase a
exaplin PKA mediated regulation of carbohydrate metabolism in the liver
- PKA regulation ensures that low blood sugar leads to increased glycogen breakdown, and decreased glycogen synthesis and glycolysis
- low blood glucose stimulates glucagon synthesis which inc concentration of cAMP which inc PKA
- PKA inc levels of phosphorylase kinase, inc glycogen phosphorylase which inc glycogen breakdown
- PKA dec glycogen synthase, dec glycogen synthesis
- PKA INC FBPase-2, DEC PFK-2, this dec [F26BP], which dec PFK-1 which dec glycolysis
- PKA dec pyruvate kinase L which dec glycolysis
how do hormones regulate enzyme activity
- coordinate tissue specific metabolism
- epinephrine has differential effects depending on the tissue
- ep in muscle inc glycogenolysis (break down glycogen)
- ep dec glycolysis in liver and inc glycolysis in the muscle
- ep inc gluconeogenesis in the liver
explain tissue specific metabolism
- Myocytes lack glucagon receptors
- Muscle pyruvate kinase is not phosphorylated by PKA
• Muscle lacks gluconeogenic enzymes
• Muscle lacks a key enzyme for glucose export
→ Muscle uses stored glycogen and glucose for itself
