carbohydrate metabolism Flashcards
wk 8
how is excess glucose stored?
as Glycogen
where are glycogen granules?
in the liver and skeletal muscle
How much of liver content is glycogen in a well-fed state?
8%
What is glycogen synthesis catalysed by?
Glycogen synthase and a branching enzyme
What are the three parts of Glycogen synthesis?
- Glucose 6 phosphate
- UDP-Glucose synthesised from G1P
- Glycogen synthesis catalysed by Glycogen synthase and a branching enzyme
What are the two parts of Glycogen Degradation?
- Catalysed by glycogen phosphorylase and debrancher enzyme.
- Glucose 6 Phosphate in liver generates free glucose from glucose 6-phosphate.
How much ATP is used to create glycogen?
2
What are the three steps of glycogen sythesis?
Phosphoglucomutase transforms G6P –> G1P
G1P reacts with Uridine-5’-triphosphate
Addition of UDP onto glycogen chains
what is the Delta G of Glycogen Synthesis?
-33.4 KJ/mol
What are the three steps of glycogen degradation (glyconeolysis)
Glycogen phosphorylase cleaves off a glucose molecule one at time
Conserves energy of the glycosidic bond by adding Phosphate to form Glucose 1-P
G1P converted to G6P using phosphoglucomutase and G6P
What enzyme is used to convert G1P into G6P?
Phoosphoglucomutase
What enzyme is used to convert G6P into G1P?
Phosphoglucomutase
How is glucose levels mechanistically regulated?
via the phosphorylation of glycogen synthase and glycogen phosphorylase
What is the role of liver with glycogen?
Makes glycogen after carbohydrate meal and degrades it during fasting.
What do skeletal muscles do with Glycogen?
Skeletal muscles: synthesis glycogen at rest and degrade it during exercise
How does Skeletal muscle metabolise glucose-6-phosphate if it has no glucose-6-phosphatase?
via glycolysis
What does PP reduce for each G6P oxidatively decarbonised?
two molecules of NADPH from NADP+
What does PPP produce?
ribose-5-phosphate
what is NADPH?
primary reductant in the cell
critical for mainatining reduced glutathione levels in cells
What is NAD+
primary oxidant
What is generated in the oxidative phase of PPP and why?
NADPH for biosynthetic pathways and detoxification of reactive O species
What occurs in the non-oxidative phases of PPP and why?
Interconverts C3-7 monosaccharides to produce ribose-5P for nucleotide synthesis.
What is the net reaction of PPP and its equation?
to generate maximum amount of NADPH
G6P + 2NADP+ –> Ribose-5-P + 2 NADPH2 + Co2
What are the three reactions of PPP?
G6P oxidised to produce 6-phospho-glucono-delta-lactone and reduces NADP+ –> NADPH2
Hydration reaction: addition of water: 6-phosphogluconolactonase forms 6-Phosphogluconate
6-phosphategluconate dehydrogenase: 6-phosphgluconate is decarboxylated (loses CO2) and reduces NADP+ –> NADPH2 to form ribose-5-P
in-terms of regulating PPP, what does Insulin promote?
G6P dehydrogenase and 6-phosphogluconate dehydrogenase activity
What is G6P dehydrogenas inhibited by?
high [NADPH]:[NADP+] ratio
What diseases are ROS associated wth?
atherosclerosis, diabetes, cancer, neurodegeneration and aging
How does NADPh protect cells from oxidative damage?
by maintaining reduced glutathione
what is glutathione?
Tripeptide with glutamate, Cycteine and glycine.
What is the functional group of glutathione?
cystenine
What are the two main reasons our livers undergo gluconeogenesis?
To maintain blood glucose and provide glucose from non-carbohydrate precursors
To use other biosynthetic precursors so that cells can make ribose.
what are other carbon sources?
amino acids, glycerol (from fats) and lactate
simply, how does gluconeogenesis differ from glycolysis?
Are opposing pathways
NOT the reverse of glycolysis
3 kinase catalysed reactions” Hexokinase, PFK1 and Pyruvate Kinase
Replaced by 4 gluconeogenic enzymes
Where does gluconeogenesis occur?
liver and the proximal convoluted tubules of the kidney
Why does gluconeogenesis occur?
If blood glucose levels are low (hypoglycaemia)
and for brain function
Why does gluconeogenesis require different enzymes than glycolysis?
because some steps of glycolysis are irreversible so it needs to use different processes.
What does pyruvate do first to begin glconeogenesis?
Enters the mitochondria, joins the TCA cycle and is converted into OAA
What enzyme concerts Acetylate into OAA?
pyruvate carboxylase
Why is OAA converted into malate in gluconeogenesis?
because OAA cant get out of the mitochondrial membrane but Malate can.
What enzyme converts OAA into PEP? And what does this enzyme do?
PEPCK
removes CO2 and adds a P
What enzyme allows f1,6BP to be converted into G6P? What does it do?
Fructose 1,6 Bisphosphoatase
Removes P from 1C
Where does G6P go to become glucose?
SER
Is more glycogen storage more in liver or muscles?
muscles= 1% but is 400g
which one is a 1 enzyme pathway?
glycogenolysis (breakdown)
what enzyme does glycogenolysis have?
glycogen phosphorylase
what occurs in glycogenolysis?
cosnevres enegy of glycosidic bonds: adds phosphate to G-1-P then convers it to G6P
what does Insulin turn on?
Glycogen synthase using protein phosphatase in which it removes P to make glycogen
What does insulin turn off?
Glycogen phosphorylase - via inhibition of protein phosphatase.
what is NADPH critical for?
getting rid of Reactive oxygen species by maintaining reduced glutathione
What is the NADPH from PPP used for?
Fatty acid synthesis, glutathione reduction and other reactions (detoxification)
Are the three reactions of PPP irreversible or reversible?
irreversible
what are some examples of ROS?
Oxyegn, superoxide anion, peroxide, hydrogen peroxide, hydroxyl radical and hydroxyl ion
how are ROC’s created?
electrons escape from the ECT and bind to O.
What is the purpose of the Cori cycle?
mechnaism that converts lactate (produced via anaerobic glycolysis) to glucose using gluconeogenic pathway
What is the cost of the Cori Cycle?
4 ATP equivalents
Where is the NADH2 used in the ETC from?
produced in the mitochondrial matrix by the bridging reaction and TCA cycle.
