12 - Glycogen Metabolism Flashcards
what is glycogenesis?
synthesis of glycogen from glucose
what is glycogenolysis?
breakdown of glycogen to form glucose
what is gluconeogenesis?
de novo (new) synthesis of glucose from metabolic precursors (lactate, amino acids, glycerol)
what is glycogen purpose?
main storage of glucose in liver & muscle
what process if the primary source of glucose overnight?
gluconeogenesis = when hepatic glycogen is depleted
what is the most efficient way to store glycogen?
if it is branched - by alpha 1-6 glycosidic links
what does glycogen consist of?
glycogen = polymer consisting of glucose molecules (joined by alpha 1-4 glycosidic link)
- branches are introduced by alpha 1-6 glycosidic link
what is required for glucose residues to be added to existing glycogen chain?
= they need to be primed
A glycogen ‘primer’ is required = This primer is a short chain of glucose residues, typically containing at least four glucose molecules
primer = covalently attached to a protein called glycogenin
describe glycogen synthesis?
- hexokinase catalyses glucose -> glucose-6-phosphate (step from glycolysis)
- phosphoglucomutase catalyses glucose-6-phosphate -> glucose-1-phosphate
- UDP-glucose pyrophosphorylase catalyses glucose-1-phosphate to UDP-glucose
- glycogen synthase catalyses UDP glucose to [glucose]n+1 which is prime substrate that then makes glycogen
what enzyme catalyses re-assignement of glucose molecule from 6th position to 1st position and why does it do this?
phosphoglucomutase
- by re-assigning glucose molecule to 1st position within glycogen chain it’s no longer readily available for glycolysis (break down of glucose for energy) = glycogen acts as storage from of glucose
what provides necessary energy for conversion in glycogenesis?
exchange for ATP, UDP can be exchanged for ATP during process of making UDP glucose, this provides the necessary energy for this conversion
= phosphate ester linkage in a nucleotide sugar releases free energy on hydrolysis
what is the primer in glycogen synthesis?
addition of glucose molecules requires a primer which is short chain of glucose residues (UDP), involves converting UDP→UTP, which serves as the prime substrate for the synthesis of the glycogen polymer
what are activated forms of
a) glucose
b) phosphate
c) acetate
a) UDP
b) ATP
c) acetyl-CoA
what is rate limiting enzyme of glycogenesis?
glycogen synthase - catalyses the transfer of a glucose molecule from UDP-glucose to the growing glycogen chain
what is process of glycogenolysis?
- glycogen phosphorylase catalyses glycogen -> glucose-1-phosphate
- phosphoglucomutase catalyes glucose-1-phosphate to glucose-6-phosphate
- glucose 6 phosphotase catalyses reaction to glucose
why does glucose-6-phosphatase need to remove phosphate in 6th position in glycogenolysis?
phosphoglucomutase = shifts to 6th position so glucose 6 phosphatase removes phosphate in 6th position to make glucose that can be transported out cell. from blood to liver via GLUT2 transporter
- glucose with phosphate in 6th position is one in a form of glucose that is primed and ready to enter glycolysis = breakdown of glucose to make energy (metabolism)
- glucose-6-phosphate will want to branch and make glycogen and that’s not what you’re wanting to do here
what is the rate limiting step of glycogenolysis?
glycogen -> glucose-1-phosphate catalysed by glycogen phosphorylase
(as 1 glucose molecule cleaved off end of glycogen at a time)
what happens to glucose-6-phosphate
a) in liver?
b) in skeletal muscle?
a) glucose 6-phosphate can be de-phosphorylated and the resulting glucose released into the blood stream
b) glucose 6-phosphate CANNOT be de-phosphorylated but instead is used to provide energy via glycolysis and the TCA cycle
what are examples of precursors that make glucose in gluconeogenesis and where do these precursors come from?
lactate - synthesised by skeletal muscle under anaerobic conditions
amino acids - derived from muscle protein by proteolysis
glycerol - derived from triglycerides by lipolysis in adipose tissue
where does energy for gluconeogenesis come from?
from oxidation of fatty acids released from adipose tissue
where does gluconeogenesis occur?
mainly in the liver, small amounts in the kidneys
what is general idea of process of gluceogenesis?
it’s basically the formation of glucose from amino acids, lactate and glycerol etc when in starvation
- it proceeds via the synthesis of oxaloacetate in mitochondria which is TCA cycle intermediate = there are actually lots of amino acid precursors that are involved in TCA cycle making it the coordination centre for drawing carbon and then repurposing it (for energy)
what are the 4 unique liver enzymes that involved in gluconeogenesis?
- pyruvate carboxylase
- PEP carboxykinase (phosphoenolpyruvate)
- fructose-1,6-bisphosphatase
- glucose-6-phosphatase
= Gluconeogenesis is NOT the reverse of glycolysis due to the need to overcome energetically unfavourable steps, catalysed by a unique set of enzymes - these are the unique enzymes that allow reaction to occur
what do the 4 unique enzymes of gluconeogenesis catalyse? (what steps)
- pyruvate carboxylase = catalyses pyruvate →oxaloacetate
- PEP carboxykinase (phosphoenolpyruvate) = catalyses oxaloacetate →phosphoenolpyruvate (PEP)
- fructose-1,6-bisphosphatase = catalyses hydrolysis of fructose-1,6-bisphosphate →fructose-6-phosphate
- glucose-6-phosphatase = catalyses glucose-6-phosphate →glucose
is fructose-2,6-biphosphate high or low in
a) fed state?
b) starved state?
a) high
b) low
what does high AMP and ADP mean?
high energy
