Biochemistry Flashcards
What is glycogenolysis?
The breakdown of glycogen to form glucose. It is accomplished by phosphorylis.
What is the main storage form of glucose in the liver and muscle cells?
Glycogen
When is liver glycogen broken down?
In between meals
What is liver glycogen released to maintain?
Blood glucose levels for red blood cells and the brain
What type of glycogen can only be consumed within the muscle cells?
Muscle glycogen
Where can muscle cells not release glycogen into?
The blood stream
What provides energy via glycolysis and the TCA cycle during bursts of physical activity?
Muscle glycogen
What does glycogenolysis fluctuate depending upon?
Meal times
What is the name of the pathway which generates new glucose from non-carbohydrate precursors?
Gluconeogenesis
What is the primary source of glucose overnight when hepatic glycogen is depleted?
Gluconeogenesis
What is a polymer consisting of single glucose molecules linked together to form chains?
Glycogen
What are glycogen molecules joined by?
An alpha 1-4 glycosidic link.
What are the branches of glycogen introduced by?
Alpha 1-6- glycosidic link.
How are new molecules added, and old molecules cleaved off from glycogen?
Free glucose joins onot the ends and glucose molecules are cleaved off the ends
What can glucose residues only be added to?
An existing glycogen chain.
What protein is found in the centre of glycogen?
Glycogenin
What substance has a catalytic activity which adds small number of glucose molecules to itself?
Glycogenin
What is the enzyme which synthesises glycogen?
Glycogensythase
What is a glycogen primer containing at least 4 glucose residues covalantly attached to?
Glycogenin
What has to first happen to glucose before it can be used for any further metabolic pathways?
It has to be phosphorylated
What is glucose phosphorylated to?
Glucose-6-phosphate
What, in the initial pathway of glycogen synthesis, traps the glucose in the cell?
Phosphorylation of glucose to glucose-6-phosphate
Once glucose has been trapped in the cell, by phosphorylation of glucose to glucose-6-phosphate - what two choices does the cell have?
If cell needs energy it can breakdown glucose-6-phosphate in glycolysis, however if plenty of glucose is present then glucose-6-phosphate can be used for the synthesis of glycogen.
Once it has been decided that glucose-6-phosphate will synthesise glycogen, what is the initial step?
Glucose-6-phosphate has to be converted to glucose-1-phosphate
What catalyses glucose-6-phosphate to glucose-1-phosphate?
Phosphoglucomutase
In the synthesis of glycogen, once glucose-6-phosphate is converted to glucose-1-phosphate by phosphoglucomutase, what then happens to the glucose-1-phosphate?
It has to be activated to form UDP-glucose
What can be considered an actived form of glucose and acts as a substrate for glycogen synthase?
UDP-glucose
In the synthesis of glycogen, once UDP-glucose is activated, what does glycogen synthase do to it?
Takes the glucose part of UDP-glucose and covalently bonds it ontop hte ends of existing glycogen.
In glycogen synthesis, what happens to the UDP that is left over, once glycogen synthase has taken the glucose part away from it?
It is phosphorylated again to form UTP
How much ATP does the phosphorylation of UDP to UTP consume?
1 ATP
For each glucose that is added to glycogen, how much ATP is consumed?
1
In glycogen synthesis, what converts glucose-1-phosphate to UDP-glucose?
UDP-glucose pyrophosphorylase
What is a nucleotide like ADP and has a uricil base, ribose sugar and 2 phosphate groups?
UDP
What makes the glucose in UDP highly active?
Attached to the second phosphate group is glucose and the bond between them makes glucose highly active.
What is - simple precursors are first converted to activated intermediates - a common pathway of?
Biosynthetic pathways
What is an activated form of phosphate?
ADP
What is an activated form of acetate?
Acetyl-CoA
What does the phosphate ester linkage in a nucleotide sugar release on hydrolysis?
Free energy
What enzyme adds on one glucose molecule (from UDP-glucose) onto the end of glycogen at one time?
Glycogen synthase
What is the rate-limiting enzyme of glycogenesis?
Glycogen synthase
What branching enzyme, introduces alpha 1-6 glycosidic branches onto glycogen?
Transglycosylase
Approximatly how many glucose residues apart is an alpha 1-6 glycosidic branched added?
10
If we need glucose, then how can muscle and liver cells remove glucose from its stored form?
By using glycogenolysis
What enzyme catalyses glycogenolysis?
Glycogen phosphorylase
What enzyme takes a glycogen molecule and cleaves one glucose off the end and adds a phosphate group to it?
Glycogen phosphorylase
What is the product of glycogen breakdown?
Glucose-phosphate
In glycogenolysis, what is glucose-1-phosphate converted to?
Glucose-6-phosphate
Where in the body, can glucose-6-phosphate be dephosphorylated and the resulting glucose released into the blood stream?
Liver
In skeletal muscle, glucose-6-phosphate cannot be dephosphorylated, so how can it provide energy?
Via glycolysis and the TCA cycle (debranching requires additional enzymes)
What transporter removes glucose from liver into blood?
GLUT2 transporter
What regulates glucogenesis and what regulates glycogenolysis
Glucogenesis - glycogen synthase
Gluconeolysis - Glycogen phosphorylase
What is the hormone of the fed state, and what does it signal the availability of?
Insulin - availability of carbohydrate in the blood stream
What does insulin stimulate the synthesis of?
Glycogen and glycogen synthase
What does insulin inhibit, at the same time as producing glycogen synthase?
Glycogen phosphorylase
What is the hormone of the starving state and what does it signal?
Glucagon - signals lack of glucose in the blood stream
What will glucagon stimulate and what will it inhibit?
Stimulate glycogenolysis and glycogen-phosphorylase
What does glucagon inhibit at the same time as stimulating glycogen-phosphorylase?
Glycogen synthase
What two other substances stimulate glycogen phosphorylase?
Adrenaline and cortisol
What diseases have increased glycogen deposits in the liver or muscle or both and each type is due to a defect in a different enzyme?
Glycogen storage diseases
What is glycogenesis?
Synthesis of glycogen from freely available glucose)
What are the three non-carbohydrate precursors for gluconeogenesis?
- Lactate (lactic acid)
- Amino acids
- Glycerol
What is produced by skeletal muscles under anaerobic conditions?
Lactate
When skeletal muscle works hard and blood cannot supply sufficient oxygen for oxygen phosphorylation, what will muscle do?
Conduct glycolysis under anaerobic conditions
During glycolysis under anaerobic conditions in skeletal muscles, what does the muscle do to re-oxidise its NADH to NAD+?
It will convert pyruvate to lactic acid
How are amino acids derived from muscle protein?
By proteolysis
What is glycerol derived from?
Triglycerides (fat storage molecules)
What does lipolysis in adipose tissue produce?
Glycerol
Gluconeogenesis is very energy consuming - where does the energy come from?
Re-oxidation of stored molecules
Where does gluconeogenesis occur?
In the liver
What are the two main methods the liver used to keep the blood sugar levels constant?
- Gluconeogenesis
2. Glycogen synthesis
Where are small amounts of glucose always synthesised?
In the kidneys
What does the energy from oxidation of fatty acids released from adipose tissue supply?
Gluconeogenesis
What three enzymes catalyse the three irreversible reactions in glycolysis?
- Hexokinase
- Phosphofructokinase
- Pyruvate kinase
Gluconeogenesis requires 4 unique liver enzymes as well as proceeding via the synthesis of what?
Oxaloacetate in mitochondria
During stage 1 of glycolysis, what converts glucose to glucose-6-phosphate?
Hexokinase
In the first stage of glycolysis, what enzyme catalyses the reversible conversion of glucose-6-phosphate to fructose-6-phosphate?
Phosphoglucose isomerase
In stage 1 of glycolysis, what occurs after the conversion of glucose-6-phosphate to fructose-6-phosphate via phosphoglucose isomerase?
Fructose-6-phosphate converts to Fructose-1,6,-bisphosphate
What enzyme catalyses the irreversible reaction during stage 1 glycolysis, of fructose-6-phosphate to fructose-1,6-bisphosphate?
Phosphofructokinase
Gluconeogenesis is energetically expensive - how much ATP is required?
6ATP
In gluconeogenesis what drives an unfavourable reaction?
ATP hydrolyses
How many pyruvates are needed to make glucose?
2
What are the two componenets of the 6ATP that are consumed to make one glucose in gluconeogenesis?
4ATP
2GTP
How much ATP is generated by glycolysis for each glucose that is oxidised?
2ATP
State the overall equation for gluconeogenesis?
2 pyruvate + 4ATP + 2GTP + 2NADH + (4H+) + 6H2O
glucose + 4ADP +2GDP + 6Pi + (2NAD+) + 2H+
Lactic acid is generated in muscle (by anaerobic exercise) - what does the muscle convert?
Pyruvate to generate ATP
To be able to continue glycolysis (in skeletal muscle anaerobic exercise), what happens to the pyruvate formed from glucose?
It is converted to lactic acid which regenerates ADP+
Why can lactic acid be so easily transported into the blood stream?
Because it is a polar molecule
Once the lactic acid is in the blood stream, after anaerobic exercise, where does it then go?
To the liver
What happens to lactic acid in the liver?
It is converted back to pyruvate and then back to glucose (costing 6ATP)
What is the Cori cycle?
- Glycolysis in muscle breaking down glucose to lactate
- Lactate moving to liver to be broken down to glucose (gluconeogenesis)
- Glucose moved back to muscle for repeat of cycle
What are the two groups of amino acids?
- Ketogenic
2. Glucogenic
What group of amino acids cannot be used for making glucose, and what group can be used as they serve as precursors for gluconeogenesis?
Ketogenic - cannot
Glucogenic - can
Where do all the glucogenic amino acids involved in gluconeogenesis enter, or become converted to?
The TCA cycle or converted to pyruvate
What does the first reaction in gluconeogenesis convert?
Pyruvate to oxaloacetate
What does gluconeogenesis proceed by?
Oxaloacetate
What can any molecule that enters the TCA cycle in one of the lower intermediates lead to the formation of?
Oxaloacetate which can then be used for glucose synthesis
What can any molecule that is converted to pyruvate also be directly converted to?
Oxaloacetate
What are ketogenic amino acids converted to?
Acetoacetyl CoA
What are the rules for ketogenic amino acids entering the TCA cycle?
- Have to be converted to acetoacetyl CoA
2. Only enter if oxaloacetate is already present
What would happen if gluconeogenesis removed oxaloacetate?
Then TCA cycle cannot further accept acetyl groups
What does glucagon signal a need for glucose in? (Pathway is related to glycolysis)?
Gluconeogenesis
In gluconeogenesis, what does glucagon stimulate?
Fructose 1,6-bisphosphatase
As well as glucagon stimulating gluconeogenesis and fructose 1,6-bisphosphatase - what else does it inhibit?
Glycolysis
Because insulin signals the availability of glucose, what does it therefore inhibit and stimulate?
Inhibits Gluconeogenesis and stimulates glycolysis
What two levels are glycolysis and gluconeogenisis regulated at?
System level - done by hormones
Individual cellular - done by allosteric effectos
What two molecules signal the requirement for energy in individual cell level regulation?
AMP or ADP
In regulation of glycolysis and gluconeogenesis, what does the stimulation of AMP or ADP cause?
Breakdown of glucose which leasd to generation of energy
What do AMP or ADP inhibit, at cellular regulation of glycolysis and gluconeogenesis?
Gluconeogenesis - energy expensive process
What happens to glycolysis and gluconeogenesis in the company of ATP?
Switch off glycolysis and stimulate gluconeogenesis
What is an intermediate of glycolysis, and is in high concentrations in the fed state and low concentrations in the starved state?
Fructose-2,6-bisphosphate
What does fructose-2,6-bisphosphate stimulate and inhibit?
Stimulates - glycolysis at high concentrations
Inhibits - gluconeogenesis
What are citric acid, alanine and acetyl CoA all important for?
Precursor molecules for biosynthetic processes
What do high concentrations of citric acid, alanne and acetyl CoA stimulate and inhibit?
Stimulate gluconeogenesis and inhibit glycolysis
What does glycolysis start and end with?
What does gluconeogenesis start and end with?
Glycolysis starts with glucose and ends with pyruvate
Gluconeogenesis starts with pyruvate and ends with glucose
In gluconeogenesis, what is the first product of the first reaction starting with pyruvate?
Oxaloacetate
What is an intermediate in the TCA cycle and is the 1-4 carbon molecule that accepts the acetyl groups in the very first step of TCA cycle?
Oxaloacetate
What are the 4 specific enzymes which are required to bypass the irreversible reactions in glycolysis?
- Pyruvate carboxylase
- PEP carboxykinase
- Fructose-1,6-bisphosphatase
- Glucose-6-phosphatase
Where does lactate enter the gluconeogenesis pathway?
Pyruvate
Where do amino acids enter the gluconeogenesis pathway?
Pyruvate and oxaloacetate (mitochondrial matrix)
Where does glycerol enter the gluconeogenesis pathway?
Dihydroxyacetone-P (before converting to fructose-1,6-bisP)
What does glucose-6-phosphatase convert?
Glucose-6-phosphate to glucose
What does fructose-1,6-bisphosphatase convert?
Fructose-1,6-bisphosphate to fructose-6-phosphate
What does pyruvate carboxylase convert in gluconeogenesis?
Pyruvate to oxaloacetate
What does PEP carboxykinase convert in gluconeogenesis?
Oxaloacetate to PEP
What is associated with disease but is also important because it is an energy source?
Fat metabolism
