Carbohydrate Catabolism & Regulation of Metabolism Flashcards
Which ONE of the following are the major organs where glycogen is stored in vertebrates?
A) Liver and Brain
B) Liver and Skeletal Muscle
C) Skeletal Muscle and Brain
D) Liver and Kidney
E) Brain and Kidney
B) Liver and Skeletal Muscle
Which ONE of the following types of reaction types is performed by glycogen phosphorylase?
A) Phosphotase
B) Kinase
C) Phosphorylysis
D) Hydrolysis
E) Carboxylation
C) Phosphorylysis
Which ONE of the following two enzyme activities is required to cleave alpha (1-6) glucose bonds during glycogen catabolism?
A) Transferase; Glucosidase
B) Kinase; Phosphotase
C) Carboxylase; Decarboxylase
D) Hydrogenase; Dehydrogenase
E) Thiolysis; Mutase
A) Transferase; Glucosidase
Which ONE of the following describes the major location for gluconeogenesis?
A) Brain, Mitochondria
B) Kidney, Cytosol
C) Liver, Mitochondria
D) Liver, Cytosol
E) Skeletal Muscle, Mitochondria
D) Liver, Cytosol
Which ONE of the following enzyme activities converts glucose 6-phosphate to glucose in the final step of gluconeogenesis?
A) Kinase
B) Mutase
C) Isomerase
D) Dehydrogenase
E) Phosphotase
E) Phosphotase
Which ONE of the following donates glucose to the growing glycogen chain during glyconeogenesis?
A) ATP
B) GTP
C) AMP
D) UDP
E) UMP
D) UDP
What is the name of the primer that glycogen is synthesised on?
A) Glycogenin
B) Pyruvate
C) Acetyl-CoA
D) Glucose 6-Phosphate
E) Carnitine
A) Glycogenin
Which ONE of the following will turn off glycolysis by allosterically binding to phosphofructokinase-1?
A) AMP
B) ADP
C) ATP
D) GDP
E) NAD
C) ATP
Which ONE of the following amino acid residues is phosphorylated to activate glycogen phosphorylase?
A) Alanine-19
B) Glutamate-26
C) Tyrosine-18
D) Serine-14
E) Tryptophan-29
D) Serine-14
High concentrations of which ONE of the following turns on glycogen phosphorylase in skeletal muscle?
A) ATP
B) GTP
C) Acetyl-CoA
D) Alanine
E) AMP
E) AMP
Which ONE of the following glucose concentrations indicates hyperglycemia?
A) 7.2 mM
B) 5.0 mM
C) 4.2 mM
D) 3.6 mM
E) 4.5 mM
A) 7.2 mM
Which ONE of the following is the Km for hexokinase IV (glucokinase) in the liver?
A) < 2.0 mM
B) > 5.0 mM
C) > 10 mM
D) < 3.6 mM
E) 4.5 mM
C) > 10 mM
Describe the structure of Glycogen
- Large polymer of glucose
- (𝛂 1-4) and (𝛃 1-6) linkages
- 12 tiers with 55, 000 glucose residues
- Built on glycogenin protein
What is Glycogen’s function?
- Readily mobilised storage form of Glucose
- Important in maintaining constant blood glucose
What happens in Step 1 of Glycogen catabolism?
inc. enzymes
Glycogen Phosphorylase (GP) sequentially removes terminal glucose residues from non-reducing end by phosphorylysis to create a lot of Glucose 1-phosphate
What happens in Step 2 of Glycogen catabolism?
inc. enzymes
- Transferase activity of “debranching enzyme” removes 3 glucose residues before branch to another tier.
- The (𝛼 1-4) Glucosidase activity of “debranching enzyme” cuts off glucose
What is the outcome of Glycogen catabolism in the liver and skeletal muscle?
- Lots of Glucose 1-phosphate is produced
- Phosphoglucomutase converts it to Glucose 6-phosphate
What are Glycogen storage diseases, their outcomes, and their treatments?
- Affect enzymes degrading and synthesising glycogen
- Result in enlarged liver, muscle wasting, and metabolic problems
- Treated with very low glucose and monitored carbohydrate diet
What is Gluconeogenesis?
The synthesis of glucose from simple non-carbohydrate percursors when glycogen stores are depleted and there is no “dietary” input of glucose
What are the THREE bypass reactions in Gluconeogenesis?
- Pyruvate to Phosphoenolpyruvate (Step 1)
- Fructose 1,6-bisphosphate to Fructose 6-phosphate (Step7)
- Glucose 6-phosphate to Glucose (Step 10)
What are the enzymes used in the THREE bypass reactions in Gluconeogenesis?
- Glucose 6-phosphotase (Step 10)
- Fructose 1,6-biphosphotase (Step 7)
- Pyruvate Carboxylase & PEP Carboxykinase (Step 1)
Describe the process of Glycogen synthesis and the major regulatory enzyme
- Step 1: glucose 6-phosphate isomerises to glucose 1-phosphate catalysed by phosphoglucomutase
- Step 2: a UDP nucleotide adds on to glucose 1-phophate
- Step 3: UDP-glucose donates glucose to the non-reducing end of a growing glycogen chain catalysed by Glycogen Synthase (the major regulatory enzyme)
- Step 4: the glycogen branching enzymes make (𝛼 1-6) branches
How and why is metabolism regulated?
- Occurs mainly at level of regulating enzyme catalysed metabolic reactions
- Needed to maintain energy and cell homeostasis
What are the mechanisms that regulate metabolic enzyme activity?
- Allosteric regulation
- Covalent modification
- Association with regulatory protein
- Sequestration
What is allosteric regulation?
Allosteric modulators change the enzyme conformation and thereby turn enzyme activity on or off
What is covalent regulation of enzyme activity?
Acts as a “molecular switch” turning the enzyme activity on or off
What is the major form of covalent regulation of enzyme activity?
Phosphorylation / Dephosphorylation
What THREE amino acids are phosphorylated in enzymes?
- Serine
- Threonine
- Tyrosine
What are the major hormones that regulate metabolism?
- Glucagon
- Insulin
- Adrenaline
Where are glucagon, insulin, and adrenaline released from?
- Glucagon - pancreas
- Insulin - pancreas
- Adrenaline - adrenal medulla
What do glucagon, insulin, and adrenaline respond to?
- Glucagon - response to HIGH blood glucose
- Insulin - response to LOW blood glucose
- Adrenaline - LOW blood glucose, anticipation, stress
How do hormones activate a metabolic signalling response?
- Act reversibly on specific receptors
- Receptors respond to hormones and regulate molecular enzyme catalysed signalling cascades in the cell
- In turn covalently modulate metabolic enzymes
Why is it important to regulate carbohydrate catabolism?
To maintain blood glucose constant
What is the normal range for blood glucose?
3.6 - 5.8 mM
How is glycogen catabolism regulated?
- Allosteric regulation
- Hormone regulation
What are the specific mechanisms that turn Glycogen Phosphorylase (GP) activity ON?
- Allosteric regulation to turn GP ON by phosphorylation and activation of Glycogen Phosphorylase A (active)
- Regulated by Glucagon and Adrenaline
What are the specfic mechanisms that turn Glycogen Phosphorylase (GP) OFF?
- When blood glucose becomes high (> 6.1mM) 1 glucose binds onto each active enzyme subunit
- Phosphoryl group cleaved off by phosphotase enzyme and inactivate GP enzyme
How/why are GP and glycogen synthase reciprocally regulated?
- So cells never break down and make glycogen at the same time
- When Glycogen Phosphorylase (GP) is on, Glycogen Synthase (GS) is off and vice versa
What are the major enzymes that are regulated in glycolysis?
- Step 1 - Hexokinase
- Step 3 - PFK-1
- Step 10 - Pyruvate Kinase
Irreversible exogonic steps
Which Hexokinase is exclusive to the liver?
HK IV
Also called glucokinase
How is Phosphofructokinase-1 (PFK1) regulated?
- Activated by HIGH concentrations of AMP & ADP (low energy indicators)
- Inhibited by HIGH concentrations of ATP & Citrate (high energy indicators)
How is PK1 regulated by Fructose 2,6-bisphosphate?
- HIGH Fructose 2,6-biphosphate (major allosteric activator in the liver) turns ON glycolysis
- REDUCING Fructose 2,6-biphosphate BLOCKS glycolysis in liver when glucose is low
How does Glucagon regulate carbohydrate catabolism/metabolism?
Increases glycogen breakdown in liver by activating glycogen phosphorylase in response to LOW blood sugar levels
How does Adrenaline regulate carbohydrate catabolism/metabolism?
Increases glycogen breakdown in muscles into glucose for fast energy in response to LOW blood sugar levels
How does Insulin regulate carbohydrate catabolism/metabolism?
Increases glycogen synthesis in liver and muscles by dephosphorylating glycogen phosphorylase in response to HIGH blood sugar levels
