metabolic pathway of glycogen Flashcards
glycogenesis
synthesis of glycogen from glucose
glycogenolysis
breakdown of glycogen to form glucose
gluconeogenesis
synthesis of glucose from metabolic precursors ie lactate/amino acids/glycerol
what is glycogen
the main storage of glucose in liver and muscle cells
*liver glycogen s broken down between meals and released to maintain blood glucose levels - muscle is more for physical activity
what are the sources of blood glucose
> glycogenolysis fluctuates dependent upon meal times
>gluconeogenesis is the primary source of glucose overnight when hepatic glycogen is depleted
the difference between glycogen of glycogenin
- glucose residues can only be added to an existing glycogen chain
- a glycogen primer containing at least 4 glucose residues is required
- the primer is covalently attached to a protein called glycogenin
glycogen synthesis
> glucose becomes glucose-6-phosphate through the action of HEXOKINASE
6-phosphate then becomes glucose-1-phosphate via PHOSPHOGLUCOMUTASE
this then becomes UDP-glucose as it binds with UTP converted from UDP via ATP, it binds via the action go glycogen synthase
this then is converted into glycogen as another molecule of glucose is added and UTP is removed
UDP glucose
“uridine diphosphate glucose”
>simple precursors are first converted to activated intermediates
>UDP can be thought of as an activated form of glucose - ATP and acetyl-CoA are activated forms of phosphate and acetate
>the phosphate ester linkage in a nucleotide sugar releases free energy on hydrolysis
glycogen synthase
this synthesis glycogen from UDP-glucose
>adds one glucose molecule to glycogen at a time
>can only extend the chains of glycogen
>cannot introduce branches
>is a rate limiting enzyme of glycogenesis
** the branching enzyme - a transglycosylase - introduces alpha 1-6 glycosidic branches into glycogen
glycogenolysis
catalysed by glycogen phosphorylase
>a rate limiting step of glycogenolysis
>one glucose molecule is cleaved off the ends of glycogen at a time
>glucose-1-phopshate is then converted to glucose-6-phosphate
> > in the liver 6-phosphate can be de-phosphorylated and the resulting glucose released into the blood stream
in skeletal muscle 6-phosphate cannot be dephosphorylated but instead is used to provide energy via glycolysis and the TCA cycle
debranching requires additional enzymes
glycogen breakdown
glycogen becomes glucose-1-phosphate via the action of glycogen phosphorylase (this is the rate limiting step)
>1-phosphate becomes 6-phosphate via the action of phosphoglucomutase
>from this it can become glucose (in the liver) via glucose-6-phosphatase or undergoes glycolysis
gluconeogenesis
> it is the synthesis of glucose within the body from precursor substrates
during prolonged starvation new glucose has to be synthesised
precursors include: lactate, amino acids, glycerol
energy comes from oxidation of fatty acids released from adipose tissue
location = in the liver mainly and small amounts in the kidney
*is not the reverse of glycolysis due to the need to overcome energetically unfavourable steps catalysed by a unique set of enzymes
glycolysis
there are three essentially irreversible reactions:
hexokinase
phosphofructokinase
pyruvate kinase
>several special reactions are required to bypass the irreversible reactions
gluconeogenesis 2
> requires four unique liver enzymes
proceeds via the synthesis of oxaloacetate in mitochondria
-the TCA cycle intermediate which accepts acetyl groups
-important for accepting acetyl groups from fat breakdown
energy consuming
stoichiometry of gluconeogenesis
2 pyruvate + 4 ATP + 2 GTP + 2 NADH + 4 H+ + 6 H2O
»»»»»
glucose + 4 ADP + 2 GDP + 6 Pi + 2 NAD+ + 2 H+
energetically expensive
>ATP hydrolysis drives an unfavourable reaction
the Cori cycle
> lactate as a precursor of gluconeogenesis formed in fast-twitch muscle under conditions of heavy exercise
blood transport lactate to liver
liver converts lactate back to glucose
glucose released into bloodstream
buys time and shifts metabolic burden from muscle to other organs
amino acids
derived from muscle protein under proteolysis
ie citric acid cycle
reciprocal regulation of glycolysis and gluconeogenesis
regulation via hormones : glucagon and insulin
> high AMP or ADP means low energy
High ATP means high energy
fructose 2,6 - biphosphate is high in fed state and low in starved state
citrate, alanine, acetyl-CoA is high when intermediated or building blocks are abundant
glycogen storage disease
groups of diseases with increased glycogen deposits in liver or muscle or both
>there are at least 10 different types (each one due to a defect in a different enzyme)
