Carbohydrates Flashcards
What are carbohydrates?
Sugars with ≥ 3C
- 1 carbonyl group (aldehyde/ketone)
- hydroxl groups
Sugars with ≥5 carbonds can form a _____ structure in 2 different configurations:
___________________
___________________
Ring structure
α: -OH down
ß: -OH up
What is the term for C1 in a carbohydrate?
Anomeric carbon
An anomeric carbon in a glucose ring can form a ____________ with another sugar to form ____________________.
Anomeric carbon → glycosidic bond
→ di/polysaccharides
What are 2 forms of starch?
1) Amylose:
- straight chain
- α1,4 linkages
2) Amylopectin
- branched chain
- - α1,4 linkages AND α1,6 linkages
Sucrose is formed from ___________________ through a ___________ glycosidic bond
Sucrose = Glucose + Fructose
- α-1,2 glycosidic bond
Lactose is formed from ___________________ through a ___________ glycosidic bond
Lactose = Glucose + Galactose
- ß-1,4 glycosidic bond
Maltose is formed from ___________________ through a ___________ glycosidic bond
Maltose = Glucose + Glucose
- α-1,4 glycosidic bond
How are starches digested by amylases?
Cleavage of α-1,4 bonds but not disaccharides
→ form (i) dextrins, (ii) maltose/isomaltose (iii) maltotriose
How are dextrins and disaccharides digested?
By brush border glycosidase complexes
Dextrins → ß-glucoamylase → glucose + isomaltose
Maltose (+ related forms)/Sucrose → Sucrose-isomaltase → glucose + fructose
Lactase → ß-glycosidase → glucose and galactose
How do deficiencies in brush border enzymes lead to diarrhea?
Accumulation of disaccharides → ↑osmolarity + bacterial breakdown
→ Acidic metabolites + H2
→ osmotic diarrhea
What enzyme is affected in lactose intolerant individuals?
Lactase (ß-glycosidase)
What are 3 etiologies for brush border enzyme deficiencies?
Acquired:
1) Injury to mucosa (eg. infective)
Genetic:
2) lactase deficiency
a) age dependent (90% asian → ~10% at 5-7 y/o)
b) Congenital
→ intolerant @ birth
3) Sucrose-isomaltase deficiency
How is lactose intolerance tested for?
1) Breath test (H2)
2) Stool acidity test (acidic metabolites)
What are 2 symptoms of lactose intolerance?
1) Osmotic diarrhea
2) Diaper rash not in folds of skin in infants
How are monosaccharides absorbed in the intestinal lumen?
1) SGLT 1 → glucose and galactose via Na+ cotransport
- Na+ gradient maintained by Na/K ATPase
2) GLUT 2 → glucose (facilitated diffusion)
3) GLUT 5 → Fructose (Facilitated diffusion)
Oral rehydration therapy involves the administration of water with ___________ to make use of the _________ enzyme to increase transport of fluids in the treatment of diarrhea.
Water + glucose + salt
- SGLT1 co-transporter
How is glucose uptake regulated by different isoforms?
GLUT 1 and 3 (most cells and brain)
- high affinity → uptake even when glucose low
GLUT 2 (pancreas and liver)
- low affinity → uptake only when glucose high
→ ↑ insulin
→ stimulate GLUT 4 and glycogen storage
GLUT 4 (muscle, adipocytes)
How does a FDG-PET scan works?
Tumour cells have higher glucose uptake (↑GLUT expression)
→ FDG (glucose analog) → ↑ uptake
→ emit positron → detect on PET scan
Which GLUT is affected by insulin?
GLUT 4 (muscle and adipocytes)
What are 3 functions of glycolysis?
1) Substrate-level phosphorylation
2) Provide substrates for further oxidation and ATP generation
3) Provide intermediates for biosynthesis and regulation
Where does glycolysis occur?
Cytoplasm of all cells
In the ______, a specialised isozyme of Hexokinase, glucokinase, ___________________.
Liver: glucokinase
- not product-inhibited
- low glucose affinity
→ permits continued P of glucose in high glucose conditions
Hexokinase _________ intracellular glucose, as G-6-P (can/cannot) cross membrane, in a (reversible/irreversible) rxn, is regulated via _______________.
Hexokinase
- traps of intracellular glucose coz G-6-P is cannot cross membrane
- irreversible
- product-inhibited (by G-6-P)
What step is the entry point and major point of of regulation in glycolysis?
Phosphorylation of F-6-P by Phospho-fructokinase-1
What are 3 enzymes that are physiologically regulated in the glycolysis pathway?
1) Hexokinase
2) Phosphofructokinase- 1
3) Pyruvate kinase
In which steps is ATP produced in glycolysis?
1) Phosphoglycerate kinase
2) Pyruvate kinase
Apart from glucose, glycolysis requires:
i) ____________ from _____________
ii) ____________ from _____________
i) NAD+ regenerated from NADH (lactate dehydrogenase)
ii) Pi from diet (limiting if trapped in sugar-phosphate forms and not metabolised eg. aldolase defiency)
What is the net equation of glycolysis?
Glucose + 2 NAD+ + 2Pi + 2ADP
→
2 Pyruvate + 2 NADH + 2H+ 2 ATP + 2 H2O
Serum lactate of >4mmol/L indicates ___________ and identifies px for aggressive resuscitation.
Poor tissue perfusion
How is NAD+ regenerated for use in glycolysis?
Anaerobic conversion of pyruvate to lactate in cytosol
- via lactate dehydrogenase
- NADH + H+ → NAD+
The (inner/outer) mitochondrial membrane is impermeable to NADH and thus requires a _________ to bring electron into the mitochondria. In this process, ___________ is regenerated.
Inner membrane impermeable to NADH
- needs a shuttle
- regenerates NAD+
What are 3 ways glycolysis in the muscle is controlled allosterically during periods of high energy demand?
1) ↑glucose → ↑F-6-P
→ PFK-2 → ↑F-2, 6-P2
→ ↑PFK-1 activity
2) ↑ATP depletion → ↑AMP
→ ↑PFK-1 activity
3) ↑F-2, 6-P2 → ↑PK activity
What are 3 ways glycolysis in the muscle is controlled allosterically during periods of low energy need/high energy state?
1) ↑ATP → inhibit PK
2) ↑ATP + ↑ Citrate → inhibit PFK-1
3) Inhibited PFK-1 → ↑ reverse rxn
→ ↑G-6-P → inhibit HK
Describe the hormonal control of glycolysis in the liver in a low glucose state?
↓Glucose → ↑Glucagon
1) → ↑P of PFK2/FBP2
→ Inactive PFK2 / Active FBP2
→ ↓F-2, 6-P2
→ ↓PFK-1 activity
→ ↓glycolysis → ↑blood glucose levels
2) ↑P of PK (inactive)
→ ↓glycolysis → ↑blood glucose levels
Describe the hormonal control of glycolysis in the liver in a high glucose state?
↑Glucose → ↑Insulin
1) → ↑de-P of PFK2/FBP2
→ Active PFK2 / Inactive FBP2
→ ↑F-2, 6-P2
→ ↑PFK-1 activity
→ ↑glycolysis → ↓blood glucose levels
2) ↑de-P of PK (active)
→ ↑glycolysis → ↓blood glucose levels
What is the role of glycolysis in oxygen transport in the blood?
RBC:
Glycolysis → 1,3-BPG
→ converted to 2,3-BPG by mutase
→ allosteric regulation of HbO2 binding
→ release O2
Low O2→ ↑2,3-BPG → ↑O2 release from HbO2 in RBC
How does pyruvate kinase deficiency lead to jaundice?
↓PK → ↓glycolysis → ↓production of NADH
(cannot replace in RBC coz no transcriptional machinery)
→ ↓ATP → cannot maintain RBC membrane → hemolysis → pre-hepatic jaundice
What are 2 ways pyruvate kinase deficiency can be compensated for?
Liver: compensatory ↑ in synthesis (RBC cannot)
RBC: cannot replace but can ↑O2 delivery by ↑2-3 BPG
How do other monosaccharides enter the glycolytic pathway?
Fructose → Dihydroxyacetone-P and Glyceraldehyde-3-P
Galactose → Glucose-6-P
Why is milk important for infants to replenish their liver glycogen stores?
Breakdown of galactose
i) → G-1P → G-6-P → Glycolytic pathway
ii) → UDP-glucose → glycogen synthesis
What is fructosuria?
Fructokinase deficiency → ↓Fructose breakdown → ↑Fructose in urine
- benign
What is fructose intolerance?
Aldolase B deficiency (Liver)
→ accumulation of F-1-P (trapped) w depletion of phosphate required for glycolysis
→ poor feeding, failure to thrive
What is classical galactosemia?
Galactose-1-P uridyltransferase deficiency
→ ↑Gal-1-P → ↑in urine
↑Gal-1-P toxic → affect liver, brain, and cataracts
How does galactosemia cause cataracts?
Galactose-1-P uridyltransferase deficiency
→ ↑Galactose→ ↑galactitol → osmotic damage to lens → cataract formation
What are the functions of the TCA cycle?
1) Generate energy
- GTP
- e- carriers (NADH, FADH2)
2) Intermediates for biosynthesis
3) Provide citrate as feedback regulator of other pathways
All of the TCA enzymes are located in the mitochondria with the exception of ________ in the _______________.
Succinic dehydrogenase (SDH) in the inner membrane
How is the TCA linked to glycolysis?
Pyruvate (from glycolysis) → Acetyl-CoA by Pyruvate Dehydrogenase (PDH)
- irreversible
The entry of pyruvate into the PCA cycle is mediated by _________________ which requires ___________________.
Pyruvate dehydrogenase
- coenzymes:
E1: Thiamine pyrophosphate
E2: Lipoate, CoA
E3: FAD, NAD+
What are 2 ways PDH activity is regulated in the TCA?
1) Allosteric regulation
+: NAD+, CoA
-: NADH
2) Phosphorylation
i) by kinase → inactive
- activated by: Acetyl-CoA, NADH (products of TCA/feedback inhibition)
- inhibited by: ADP, pyruvate
ii) dephosphorylated by phosphotase
- activated by Muscle activity (Ca2+)
Describe the regulation of PDH during excercise.
Exercise → ↑Energy Dd
1) ↑NAD+ and CoA → ↑PDH activity
2) Muscle activity → ↑Ca2+ → Phosphatase → ↑de-P of PDH complex → ↑PDH activity
3) ↑ADP and pyruvate → inhibit Kinase → ↑PDH activity
Describe the regulation of PDH during rest.
Rest → ↓Energy Dd
1) ↑NADH → inhibit PDH
2) ↑Acetyl-CoA → ↑NADH
- both ↑kinase activity → ↑P of PDH (inactive)
What are 3 substrates that can be converted to Acetyl-CoA and enter the TCA other than pyruvate?
1) Ethanol
2) Alanine (amino acid)
3) Fatty acid
4) Ketone bodies
What is the net equation for 1 TCA cycle?
Acetyl-CoA + 3 NAD+ + FAD
2 CO2 + CoA + 3NADH + 3H+ FAD (2H) + GTP
Condensation of Oxaloacetate and Acetyl-CoA is a (reversible/irreversible reaction) by citrate synthase and inhibited by _______________.
Irreversible
- inhibited by citrate (product inhibition)
What is the rate limiting step of the TCA cycle?
Oxidative decarboxylation of isocitrate
The oxidative decarboxylation of α-KG to Succinyl-CoA is mediated by α-KG dehydrogenase and requires ___________________.
1) TPP
2) Lipoate
3) FAD
4) NAD+, CoA
In which step is GTP produced in the TCA cycle?
Substrate-level phosphorylation
Succinyl CoA → Succinate Thiokinase → Succinate
In which step are e- carriers produced in the TCA cycle?
Dehydrogenation/Oxidation
1) Of Succinate → Fumarate (FADH2)
2) Of Malate → Oxaloacetate (NADH)
True or false:
Intermediates for the TCA cycle can be replenished by increasing the entry of Acetyl-CoA to increase carbon.
False
- no net replenishment (2C from Acetyl-CoA → 2 CO2)
- needs anaplerotic rxn (pyruvate, amino acids, fatty acids)
What is the main anaplerotic reaction in the TCA cycle?
Pyruvate + HCO3- → Oxaloacetate
- ATP → ADP + Pi
- via Pyruvate decarboxylase
- needs biotin (vit. B7)
- activated by acetyl-CoA
What are 4 ways the TCA cycle is regulated?
1) Isocitrate DH (rate-limiting)
+: ADP (low energy), Ca2+ (muscle use)
-: NADH
2) α-KG DH
+: Ca2+ (muscle use)
-: NADH
3) Malate DH
-: NADH
4) Citrate synthase
-: citrate (product)
Describe the regulation of the TCA during periods of high energy need.
↑Energy need → ↑ADP, ↓NADH
1) ↑ADP + Ca2+ → ↑Isocitrate DH activity
2) ↑Ca2+ → ↑ α-KG DH activity
Describe the regulation of the TCA during periods of low energy need.
↓Energy need → ↓ADP, ↑NADH
1) ↑NADH → inhibit:
a) Isocitrate DH
b) α-KG DH
c) Malate DH
2) TCA cycle slows → ↑citrate → inhibit citrate synthase
Why does a low carb, high fat diet help those with pyruvate dehydrogenase deficiency?
Bypass block:
Fat → Acetyl CoA
Why does pyruvate dehydrogenase deficiency cause a (i) acid-base pathology and (ii) neurodegeneration?
↓pyruvate dehydrogenase activity
i) → ↑pyruvate
→ ↑conversion to lactate
→ lactic acidosis
ii) ↓Acetyl-CoA → ↓TCA/ATP
→ neurodegeneration
How do fumarase, succinate DH, and α-KG DH deficiencies present?
1) Lactic acidosis
2) Neurological dysfunction
Thiamine deficiency is (acquired/genetic) and affects ___________ enzymes, usually presenting as _______________________
Acquired (BeriBeri)
Required for Pyruvate DH and α-KG DH function → ↓ATP
→ Cardiac/Neurological dysfunction
What is the pathogenesis of Arsenic/mercury poisoning?
Both inhibit lipoic acid (cofactor for pyruvate DH and αKG DH)
→ ↓ATP
→ neurological dysfunction, organ failure, death
How does acute arsenic poisoning (usually rat poison) differ from chronic?
Presentation:
Acute: Garlicky odor (from reaction w stomach acid)
Chronic:
- “dew drops on dusty road” on palms
- Mees lines on fingernails
What is the function of oxidative phosphorylation?
Generate ATP from reducing equivalents (NADH/FADH2)
How does NADH from glycolysis in the cytoplasm enter the mitochondria?
Shuttles:
1) Glycerol-3-phosphate
NADH + H+ → FADH2
- fast but less ATP yield
2) Malate-aspartate
NADH + H+ → NADH + H+
- slower but more ATP yield
What are the components of the ETC?
Complex I: NADH-Q oxidoreductase
- transfer e- from NADH to CoQ
Complex II: Succinate-Q reductase
- transfer e- from FADH2 to CoQ
Complex III: Q-cytochrome C oxidoreductase
- transfer e- from CoQ to Cytochrome C
Complex IV: Cytochrome C oxidase
- transfer e- from Cytochrome C to O2→Water
Which of the ETC membrane complexes pump H+ across the inner membrane to generate a proton gradient?
Complex 1, 3, 4 (transmembrane)
- NOT complex 2 (inner side)
Where does FADH2 transferring e- to CoQ come from?
1) Via Complex II/Succinate-Q reductase from TCA
2) Via Glycerol-3-P shuttle
- NADH + H+ from glycolysis → FADH2
3) Lipid metabolism (via ß-oxidation)
How is ATP produced in oxidative phosphorylation?
1) Generative of proton motive force
- Complex I-4 use NADH and FADH2 to pump H+ (except 2) across membrane
2) Chemiosmosis of H+ back into matrix causes rotation of ATP synthase stalk
→ conformational change in F1 subunit
→ P and release of ATP
(1 rotation → 3 ATP)
What are 2 side products of oxidative phosphorylation?
1) ROS
- from partial reduction of O2 (needs 4 e-)
2) Heat
- when proton gradient dissipated via UCP (uncoupling protein) in brown fat
What are 3 physiological defenses against ROS produced in oxidative phosphorylation?
1) H2O2 → O2 → H2O
a) Superoxide dismutase: superoxide → O2 and H2O2
b) Catalase: H2O2 → O2 + H2O
c) Glutathione peroxidase:
H2O2 → H2O
Reduced Glutathione → Oxidised Glutatione
2) Antioxidants (eg. Vit. C and E)
3) ß-carotene
How is oxidative phosphorylation regulated?
Energy consumption
ATP levels ~ ATP levels in matrix
↑ATP → ↓oxphos
v.v.
What determines the manifestation of OXPHOS mitochondrial disease phenotypes?
Maternal inheritance and replicative segregation
What is the pathogenesis of MELAS syndrome?
OXPHOS mitochondrial disease
Mutation in tRNA gene → ↓ETC complexes
→ ↓ATP → organ dysfunction in those req high energy (eg. muscle and brain)
→ ↓pyruvate in TCA → ↑lactate
What do mitochondrial poisons eg. Rotenone, Antimycin A, Cyanide, CO usually target?
OXPHOS membrane complexes
What are 2 functions of the hexose monophosphate shunt?
1) Generate NADPH
2) Generate R-5-P to nucleotide biosynthesis
Where is the HMP shunt usually functioning?
Cytoplasm of tissues w high usage of NADPH or rapidly dividing cells.
eg.
1) Adipocytes (FA synthesis)
2) Hepatocytes (FA and Drug metabolism)
3) Adrenal cortex/Gonads (Steroid synthesis)
4) RBC (glutathione reduction)
5) WBC (superoxide generation)
What is the rate limiting step of the hexose monophosphate shunt?
Oxidative (Irreversible)
- via G6PD
- inhibited by NADPH
What is the oxidative phase of the hexose monophosphate shunt?
Irreverisble generation of NADPH and R-5-P from NADP+ and G-6-P
G-6-P → G6PD enzyme (rate limiting) (inhibited by NADPH)
6-phosphoglucono-δ-lactone → gluconolactonase → 6-phosphogluconate
→ 6-phosphogluconate dehydrogenase → R-5-P + NADPH
What is the non-oxidative phase of the hexose monophosphate shunt?
Reversible
- Isomerisation of R-5-P
- Recycling of excess R-5-P back into glycolysis
- via Transketolases (2C) and Transaldolases (3C)
Transketolases used in the non-oxidative phase of the hexose monophosphate shunt require what compound to function?
Thiamine pyrophosphate
- transketolase activity in RBC used as assay for thiamine levels
How is the HMP shunt regulated?
@ G6PD
- rate determined by NADPH/NADP+ ratio
↓NADP+ → ↑HMP shunt
What are 4 functions of NADPH?
1) Reductive biosynthesis
2) Detoxification rxn
3) Generate ROS
4) Synthesise NO
5) Glutathione reduction
Why does a NADPH oxidase deficiency lead to chronic granulomatous disease?
Inability to generate ROS in WBC
- can engulf but cannot kill → form granulomas
How does NAPDH aid in preventing hemolysis in RBCs due to oxidative stress?
Oxidative stress → ↑H2O2
- converted to H2O by glutathione peroxidase (using reduced glutathione)
- resultant oxidised glutathione → reduced by glutathione reductase (using NADPH)
G6PD deficiency follows a ________________ inheritance pattern and presents variably from asymptomatic to __________________.
XLR pattern
- asymptomatic to sever hemolytic anemia
How is hemolytic anemia precipitated in G6PD deficient individuals?
↑oxidative stress (eg. drugs, herbal medication, moth balls, infection)
How does G6PD deficiency lead to (i) prehepatic jaundice and (ii) Heinz bodies
G6PD deficiency → ↓regeneration of NADPH via oxidative phase of HMP shunt
→ ↓regeneration of reduced glutathione from oxidised form
→ accumulation of ROS
→ oxidation of proteins
i) ↓membrane plasticity → hemolysis
ii) denaturation → Heinz bodies
G6PD deficiency may confer resistance to __________ by preventing _______ utilization by plasmodium in RBCs
G6PD deficiency may confer resistance to malaria by preventing NAPDH utilization by plasmodium in RBCs
Where does gluconeogenesis occur?
Primarily in liver and kidney
Mostly cytosolic except:
1) Pyruvate carboxylase (mitochondria)
2) Glucose-6-Phosphatase (ER)
How is pyruvate converted to phosphoenolpyruvate (PEP) in (1st 2 steps) gluconeogenesis?
1) Pyruvate → Oxaloacetate (mitochondria)
- needs biotin
- via pyruvate carboxylase (+: acetyl CoA)
2) Shuttling of oxaloacetate into cytosol via interconversion to malate
- by malate dehydrogenase
3) Decarboxylation using GTP
- Oxaloacetate → PEP
Why can gluconeogenesis not just be glycolysis in reverse?
Need to overcome 3 irreversible steps:
1) Pyruvate → PEP
2) Fructose 1, 6-P2 → F-6-P
3) G-6-P → Glucose
Which enzyme is required for exporting glucose our of the cell?
Glucose-6-Phosphatase
True or false.
Gluconeogenesis is thermodynamically favorable.
True
ΔG= -48kJ/Mol
vs reverse glycolysis= 84kJ/mol
What are 3 substrates for gluconeogenesis?
1) Pyruvate
- lactate
- alanine
- other amino acids
2) Oxaloacetate
- glutamine
- other amino acids
3) Glycerol-3-P
- Glycerol
What is the Cori cycle?
Lactate from RBC and muscles
→ transported to liver
→ generate pyruvate via lactate DH
→ Glucose
→ exported back to muscles and blood
How is gluconeogenesis regulated?
1) Allosteric
a) High energy:
↑ATP + ↑ Citrate
→ ↑F-1, 6-BP activity
→ ↑Gluconeogenesis
↑Acetyl CoA → ↑PC activity
→ ↑Gluconeogenesis
b) Low energy:
↑ADP → inhibit PC and PEPCK → ↓Gluconeogenesis
↑AMP →Inhibit F-1, 6-BP → ↓Gluconeogenesis
2) Hormones
a) Transcription of gluconeogenesis enzymes
- when fasted → glucagon
b) F-2, 6-P2
- Insulin → ↑F-2, 6-P2 → inhibit F-1, 6-BP
- Glucagon → ↓F-2, 6-P2 → ↑F-1, 6-BP activity → ↑Gluconeogenesis
What is the pathogenesis of Glucose-6-phosphatase deficiency?
Genetic Glucose-6-phosphatase deficiency
↑G-6-P
1) → HMP shunt → ↑nucleotide metab → ↑uric acid
2) ↑ Glycogen → organomegaly
3) → ↑Pyruvate → ↑lactate
What is the pathogenesis of Pyruvate carboxylase deficiency?
↑pyruvate
→ ↑lactate
→ ↑Acetyl-CoA
→ ↓Oxaloacetate → ↓TCA → ↓ATP
Muscle glycogen provides short term energy during _______ while liver glycogen provides it during _______________.
Muscle: exercise
Liver: fasting
Which organ contains the most amount of glycogen?
Muscle
What is the major regulation point for glycogen synthesis?
Lengthening of glycogen primer by α-1,4-linkages by glycogen synthase
Branching of glycogen molecules is done by establishing __________ linkages and have 2 benefits: ______________________.
α-1,6 linkages
Branching:
↑Sites for synthesis/degradation
↑solubility
What is the major regulation point for glycogen breakdown?
Release of G-1-P by cleavage of α-1,4 linkages by glycogen phosphorylase
(diff isoforms → tissue-specific regulation)
Other than glycogen phosphorylase, what other enzyme releases of G-1-P by cleavage of α-1,4 linkages?
Lysosomal α-1,4-glucosidase (1-3%)
Describe the allosteric regulation of glycogen metabolism in the liver in a fed state.
Fed state:
a) ↑ glucose ↑ G-6-P ↑ATP
→ inhibit Glycogen phosphorylase
→ ↓glycogenolysis
b) ↑ G-6-P → activate glycogen synthase
→ ↑glycogenesis
Describe the allosteric regulation of glycogen metabolism in the liver in a fasted state.
Fed state:
↓glucose ↓G-6-P ↓ATP
→ no inhibition of Glycogen phosphorylase
→ ↑glycogenolysis
→ ↑G-1-P → ↑UDP → inhibit glycogen synthase
→ ↓glycogenesis
Describe the allosteric regulation of glycogen metabolism in the muscle in a active state.
High energy need:
a) ↑ AMP → ↑ Glycogen phosphorylase activity
b) ↑Ca → ↑Calmodulin → ↑P and activation of Glycogen phosphorylase
→ ↑glycogenolysis
→ ↑G-1-P → ↑UDP → inhibit glycogen synthase
→ ↓glycogenesis
Describe the allosteric regulation of glycogen metabolism in the muscle in a resting state.
Low energy need:
a) ↑ ATP ↑G-6-P
→ inhibit Glycogen phosphorylase
→ ↓glycogenolysis
b) ↑ G-6-P → activate glycogen synthase
→ ↑glycogenesis
How does insulin regulate glycogen metabolism?
High glucose → ↑insulin
→ bind to RTK → P IRS (insulin receptor substrate)
→ Activate Protein phosphatase-1
a) Dephosphorylate glycogen synthase → active → ↑glycogenesis
b) Dephosphorylate glycogen phosphorylase → inactive → ↓glycogenolysis
True or false:
Glucagon and epinephrine both act on both liver and muscle tissue to induce glycogenolysis and inhibit glycogenesis.
False
Glucagon → ONLY Liver
Epinephrine → Liver and muscle
How does glucagon and epinephrine regulate glycogen metabolism?
Low glucose/Sympathetic response → ↑glucagon
→ bind to GPCR → release α-subunit
→ activate adenylate cyclase → (ATP→cAMP)
→ activate Protein Kinase A
a) → P glycogen synthase (inactive)
→ ↓glycogenesis
b) → P phosphorylase kinase → P glycogen phosphorylase
→ ↑glycogenolysis
What type of glycogen storage disease, enzyme and organ affected for:
- Fasting hypoglycemia
- Organomegaly
- ↑lactate/uric acid
Type I (Von Gierke)
- Glucose -6-Phosphatase
- Liver and kidney affected
What type of glycogen storage disease, enzyme and organ affected for:
- Myopathy
- Cardiac Failure
Type II (Pompe)
- 1-4 Glucosidase (minor enzyme → no hypoglycemia)
- General (lysosomal) affected
What type of glycogen storage disease, enzyme and organ affected for:
- Fasting hypoglycemia
- Hepatomegaly
- Muscle weakness
Type III (Cori)
- 4-4 transferase and/or 1-6 glucosidase
- Liver, muscle, heart affected
What type of glycogen storage disease, enzyme and organ affected for:
- Hepatosplenomegaly
- Early Death
Type IV (Andersen)
- Branching enzyme
- Liver
What type of glycogen storage disease, enzyme and organ affected for:
- Exercise-induced muscle pain
- Cramps
Type V (McArdle)
- Muscle glycogen phosphorylase
- skeletal muscle
