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Metabolism and Biochem > Carbohydrates > Flashcards

Carbohydrates Flashcards

1
Q

What are carbohydrates?

A

Sugars with ≥ 3C
- 1 carbonyl group (aldehyde/ketone)
- hydroxl groups

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2
Q

Sugars with ≥5 carbonds can form a _____ structure in 2 different configurations:
___________________
___________________

A

Ring structure
α: -OH down
ß: -OH up

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3
Q

What is the term for C1 in a carbohydrate?

A

Anomeric carbon

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4
Q

An anomeric carbon in a glucose ring can form a ____________ with another sugar to form ____________________.

A

Anomeric carbon → glycosidic bond
→ di/polysaccharides

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5
Q

What are 2 forms of starch?

A

1) Amylose:
- straight chain
- α1,4 linkages

2) Amylopectin
- branched chain
- - α1,4 linkages AND α1,6 linkages

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6
Q

Sucrose is formed from ___________________ through a ___________ glycosidic bond

A

Sucrose = Glucose + Fructose
- α-1,2 glycosidic bond

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7
Q

Lactose is formed from ___________________ through a ___________ glycosidic bond

A

Lactose = Glucose + Galactose
- ß-1,4 glycosidic bond

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8
Q

Maltose is formed from ___________________ through a ___________ glycosidic bond

A

Maltose = Glucose + Glucose
- α-1,4 glycosidic bond

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9
Q

How are starches digested by amylases?

A

Cleavage of α-1,4 bonds but not disaccharides
→ form (i) dextrins, (ii) maltose/isomaltose (iii) maltotriose

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10
Q

How are dextrins and disaccharides digested?

A

By brush border glycosidase complexes

Dextrins → ß-glucoamylase → glucose + isomaltose

Maltose (+ related forms)/Sucrose → Sucrose-isomaltase → glucose + fructose

Lactase → ß-glycosidase → glucose and galactose

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11
Q

How do deficiencies in brush border enzymes lead to diarrhea?

A

Accumulation of disaccharides → ↑osmolarity + bacterial breakdown
→ Acidic metabolites + H2
→ osmotic diarrhea

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12
Q

What enzyme is affected in lactose intolerant individuals?

A

Lactase (ß-glycosidase)

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13
Q

What are 3 etiologies for brush border enzyme deficiencies?

A

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

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14
Q

How is lactose intolerance tested for?

A

1) Breath test (H2)
2) Stool acidity test (acidic metabolites)

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15
Q

What are 2 symptoms of lactose intolerance?

A

1) Osmotic diarrhea
2) Diaper rash not in folds of skin in infants

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16
Q

How are monosaccharides absorbed in the intestinal lumen?

A

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)

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17
Q

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.

A

Water + glucose + salt
- SGLT1 co-transporter

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18
Q

How is glucose uptake regulated by different isoforms?

A

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)

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19
Q

How does a FDG-PET scan works?

A

Tumour cells have higher glucose uptake (↑GLUT expression)
→ FDG (glucose analog) → ↑ uptake
→ emit positron → detect on PET scan

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20
Q

Which GLUT is affected by insulin?

A

GLUT 4 (muscle and adipocytes)

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21
Q

What are 3 functions of glycolysis?

A

1) Substrate-level phosphorylation

2) Provide substrates for further oxidation and ATP generation

3) Provide intermediates for biosynthesis and regulation

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22
Q

Where does glycolysis occur?

A

Cytoplasm of all cells

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23
Q

In the ______, a specialised isozyme of Hexokinase, glucokinase, ___________________.

A

Liver: glucokinase
- not product-inhibited
- low glucose affinity
→ permits continued P of glucose in high glucose conditions

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24
Q

Hexokinase _________ intracellular glucose, as G-6-P (can/cannot) cross membrane, in a (reversible/irreversible) rxn, is regulated via _______________.

A

Hexokinase
- traps of intracellular glucose coz G-6-P is cannot cross membrane
- irreversible
- product-inhibited (by G-6-P)

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25
Q

What step is the entry point and major point of of regulation in glycolysis?

A

Phosphorylation of F-6-P by Phospho-fructokinase-1

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26
Q

What are 3 enzymes that are physiologically regulated in the glycolysis pathway?

A

1) Hexokinase
2) Phosphofructokinase- 1
3) Pyruvate kinase

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27
Q

In which steps is ATP produced in glycolysis?

A

1) Phosphoglycerate kinase
2) Pyruvate kinase

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28
Q

Apart from glucose, glycolysis requires:
i) ____________ from _____________
ii) ____________ from _____________

A

i) NAD+ regenerated from NADH (lactate dehydrogenase)

ii) Pi from diet (limiting if trapped in sugar-phosphate forms and not metabolised eg. aldolase defiency)

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29
Q

What is the net equation of glycolysis?

A

Glucose + 2 NAD+ + 2Pi + 2ADP
→
2 Pyruvate + 2 NADH + 2H+ 2 ATP + 2 H2O

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30
Q

Serum lactate of >4mmol/L indicates ___________ and identifies px for aggressive resuscitation.

A

Poor tissue perfusion

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31
Q

How is NAD+ regenerated for use in glycolysis?

A

Anaerobic conversion of pyruvate to lactate in cytosol
- via lactate dehydrogenase
- NADH + H+ → NAD+

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32
Q

The (inner/outer) mitochondrial membrane is impermeable to NADH and thus requires a _________ to bring electron into the mitochondria. In this process, ___________ is regenerated.

A

Inner membrane impermeable to NADH
- needs a shuttle
- regenerates NAD+

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33
Q

What are 3 ways glycolysis in the muscle is controlled allosterically during periods of high energy demand?

A

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

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34
Q

What are 3 ways glycolysis in the muscle is controlled allosterically during periods of low energy need/high energy state?

A

1) ↑ATP → inhibit PK

2) ↑ATP + ↑ Citrate → inhibit PFK-1

3) Inhibited PFK-1 → ↑ reverse rxn
→ ↑G-6-P → inhibit HK

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35
Q

Describe the hormonal control of glycolysis in the liver in a low glucose state?

A

↓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

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36
Q

Describe the hormonal control of glycolysis in the liver in a high glucose state?

A

↑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

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37
Q

What is the role of glycolysis in oxygen transport in the blood?

A

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

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38
Q

How does pyruvate kinase deficiency lead to jaundice?

A

↓PK → ↓glycolysis → ↓production of NADH
(cannot replace in RBC coz no transcriptional machinery)

→ ↓ATP → cannot maintain RBC membrane → hemolysis → pre-hepatic jaundice

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39
Q

What are 2 ways pyruvate kinase deficiency can be compensated for?

A

Liver: compensatory ↑ in synthesis (RBC cannot)

RBC: cannot replace but can ↑O2 delivery by ↑2-3 BPG

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40
Q

How do other monosaccharides enter the glycolytic pathway?

A

Fructose → Dihydroxyacetone-P and Glyceraldehyde-3-P

Galactose → Glucose-6-P

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41
Q

Why is milk important for infants to replenish their liver glycogen stores?

A

Breakdown of galactose
i) → G-1P → G-6-P → Glycolytic pathway
ii) → UDP-glucose → glycogen synthesis

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42
Q

What is fructosuria?

A

Fructokinase deficiency → ↓Fructose breakdown → ↑Fructose in urine
- benign

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43
Q

What is fructose intolerance?

A

Aldolase B deficiency (Liver)
→ accumulation of F-1-P (trapped) w depletion of phosphate required for glycolysis

→ poor feeding, failure to thrive

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44
Q

What is classical galactosemia?

A

Galactose-1-P uridyltransferase deficiency
→ ↑Gal-1-P → ↑in urine
↑Gal-1-P toxic → affect liver, brain, and cataracts

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45
Q

How does galactosemia cause cataracts?

A

Galactose-1-P uridyltransferase deficiency
→ ↑Galactose→ ↑galactitol → osmotic damage to lens → cataract formation

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46
Q

What are the functions of the TCA cycle?

A

1) Generate energy
- GTP
- e- carriers (NADH, FADH2)

2) Intermediates for biosynthesis

3) Provide citrate as feedback regulator of other pathways

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47
Q

All of the TCA enzymes are located in the mitochondria with the exception of ________ in the _______________.

A

Succinic dehydrogenase (SDH) in the inner membrane

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48
Q

How is the TCA linked to glycolysis?

A

Pyruvate (from glycolysis) → Acetyl-CoA by Pyruvate Dehydrogenase (PDH)
- irreversible

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49
Q

The entry of pyruvate into the PCA cycle is mediated by _________________ which requires ___________________.

A

Pyruvate dehydrogenase
- coenzymes:
E1: Thiamine pyrophosphate
E2: Lipoate, CoA
E3: FAD, NAD+

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50
Q

What are 2 ways PDH activity is regulated in the TCA?

A

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+)

51
Q

Describe the regulation of PDH during excercise.

A

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

52
Q

Describe the regulation of PDH during rest.

A

Rest → ↓Energy Dd
1) ↑NADH → inhibit PDH

2) ↑Acetyl-CoA → ↑NADH
- both ↑kinase activity → ↑P of PDH (inactive)

53
Q

What are 3 substrates that can be converted to Acetyl-CoA and enter the TCA other than pyruvate?

A

1) Ethanol
2) Alanine (amino acid)
3) Fatty acid
4) Ketone bodies

54
Q

What is the net equation for 1 TCA cycle?

A

Acetyl-CoA + 3 NAD+ + FAD

2 CO2 + CoA + 3NADH + 3H+ FAD (2H) + GTP

55
Q

Condensation of Oxaloacetate and Acetyl-CoA is a (reversible/irreversible reaction) by citrate synthase and inhibited by _______________.

A

Irreversible
- inhibited by citrate (product inhibition)

56
Q

What is the rate limiting step of the TCA cycle?

A

Oxidative decarboxylation of isocitrate

57
Q

The oxidative decarboxylation of α-KG to Succinyl-CoA is mediated by α-KG dehydrogenase and requires ___________________.

A

1) TPP
2) Lipoate
3) FAD
4) NAD+, CoA

58
Q

In which step is GTP produced in the TCA cycle?

A

Substrate-level phosphorylation
Succinyl CoA → Succinate Thiokinase → Succinate

59
Q

In which step are e- carriers produced in the TCA cycle?

A

Dehydrogenation/Oxidation
1) Of Succinate → Fumarate (FADH2)
2) Of Malate → Oxaloacetate (NADH)

60
Q

True or false:
Intermediates for the TCA cycle can be replenished by increasing the entry of Acetyl-CoA to increase carbon.

A

False
- no net replenishment (2C from Acetyl-CoA → 2 CO2)
- needs anaplerotic rxn (pyruvate, amino acids, fatty acids)

61
Q

What is the main anaplerotic reaction in the TCA cycle?

A

Pyruvate + HCO3- → Oxaloacetate
- ATP → ADP + Pi
- via Pyruvate decarboxylase
- needs biotin (vit. B7)
- activated by acetyl-CoA

62
Q

What are 4 ways the TCA cycle is regulated?

A

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)

63
Q

Describe the regulation of the TCA during periods of high energy need.

A

↑Energy need → ↑ADP, ↓NADH

1) ↑ADP + Ca2+ → ↑Isocitrate DH activity

2) ↑Ca2+ → ↑ α-KG DH activity

64
Q

Describe the regulation of the TCA during periods of low energy need.

A

↓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

65
Q

Why does a low carb, high fat diet help those with pyruvate dehydrogenase deficiency?

A

Bypass block:
Fat → Acetyl CoA

66
Q

Why does pyruvate dehydrogenase deficiency cause a (i) acid-base pathology and (ii) neurodegeneration?

A

↓pyruvate dehydrogenase activity

i) → ↑pyruvate
→ ↑conversion to lactate
→ lactic acidosis

ii) ↓Acetyl-CoA → ↓TCA/ATP
→ neurodegeneration

67
Q

How do fumarase, succinate DH, and α-KG DH deficiencies present?

A

1) Lactic acidosis
2) Neurological dysfunction

68
Q

Thiamine deficiency is (acquired/genetic) and affects ___________ enzymes, usually presenting as _______________________

A

Acquired (BeriBeri)
Required for Pyruvate DH and α-KG DH function → ↓ATP
→ Cardiac/Neurological dysfunction

69
Q

What is the pathogenesis of Arsenic/mercury poisoning?

A

Both inhibit lipoic acid (cofactor for pyruvate DH and αKG DH)
→ ↓ATP
→ neurological dysfunction, organ failure, death

70
Q

How does acute arsenic poisoning (usually rat poison) differ from chronic?

A

Presentation:
Acute: Garlicky odor (from reaction w stomach acid)

Chronic:
- “dew drops on dusty road” on palms
- Mees lines on fingernails

71
Q

What is the function of oxidative phosphorylation?

A

Generate ATP from reducing equivalents (NADH/FADH2)

72
Q

How does NADH from glycolysis in the cytoplasm enter the mitochondria?

A

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

73
Q

What are the components of the ETC?

A

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

74
Q

Which of the ETC membrane complexes pump H+ across the inner membrane to generate a proton gradient?

A

Complex 1, 3, 4 (transmembrane)
- NOT complex 2 (inner side)

75
Q

Where does FADH2 transferring e- to CoQ come from?

A

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)

76
Q

How is ATP produced in oxidative phosphorylation?

A

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)

77
Q

What are 2 side products of oxidative phosphorylation?

A

1) ROS
- from partial reduction of O2 (needs 4 e-)

2) Heat
- when proton gradient dissipated via UCP (uncoupling protein) in brown fat

78
Q

What are 3 physiological defenses against ROS produced in oxidative phosphorylation?

A

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

79
Q

How is oxidative phosphorylation regulated?

A

Energy consumption
ATP levels ~ ATP levels in matrix
↑ATP → ↓oxphos
v.v.

80
Q

What determines the manifestation of OXPHOS mitochondrial disease phenotypes?

A

Maternal inheritance and replicative segregation

81
Q

What is the pathogenesis of MELAS syndrome?

A

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

82
Q

What do mitochondrial poisons eg. Rotenone, Antimycin A, Cyanide, CO usually target?

A

OXPHOS membrane complexes

83
Q

What are 2 functions of the hexose monophosphate shunt?

A

1) Generate NADPH
2) Generate R-5-P to nucleotide biosynthesis

84
Q

Where is the HMP shunt usually functioning?

A

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)

85
Q

What is the rate limiting step of the hexose monophosphate shunt?

A

Oxidative (Irreversible)
- via G6PD
- inhibited by NADPH

86
Q

What is the oxidative phase of the hexose monophosphate shunt?

A

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

87
Q

What is the non-oxidative phase of the hexose monophosphate shunt?

A

Reversible
- Isomerisation of R-5-P
- Recycling of excess R-5-P back into glycolysis

  • via Transketolases (2C) and Transaldolases (3C)
88
Q

Transketolases used in the non-oxidative phase of the hexose monophosphate shunt require what compound to function?

A

Thiamine pyrophosphate

  • transketolase activity in RBC used as assay for thiamine levels
89
Q

How is the HMP shunt regulated?

A

@ G6PD
- rate determined by NADPH/NADP+ ratio

↓NADP+ → ↑HMP shunt

90
Q

What are 4 functions of NADPH?

A

1) Reductive biosynthesis
2) Detoxification rxn
3) Generate ROS
4) Synthesise NO
5) Glutathione reduction

91
Q

Why does a NADPH oxidase deficiency lead to chronic granulomatous disease?

A

Inability to generate ROS in WBC
- can engulf but cannot kill → form granulomas

92
Q

How does NAPDH aid in preventing hemolysis in RBCs due to oxidative stress?

A

Oxidative stress → ↑H2O2

  • converted to H2O by glutathione peroxidase (using reduced glutathione)
  • resultant oxidised glutathione → reduced by glutathione reductase (using NADPH)
93
Q

G6PD deficiency follows a ________________ inheritance pattern and presents variably from asymptomatic to __________________.

A

XLR pattern
- asymptomatic to sever hemolytic anemia

94
Q

How is hemolytic anemia precipitated in G6PD deficient individuals?

A

↑oxidative stress (eg. drugs, herbal medication, moth balls, infection)

95
Q

How does G6PD deficiency lead to (i) prehepatic jaundice and (ii) Heinz bodies

A

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

96
Q

G6PD deficiency may confer resistance to __________ by preventing _______ utilization by plasmodium in RBCs

A

G6PD deficiency may confer resistance to malaria by preventing NAPDH utilization by plasmodium in RBCs

97
Q

Where does gluconeogenesis occur?

A

Primarily in liver and kidney
Mostly cytosolic except:
1) Pyruvate carboxylase (mitochondria)
2) Glucose-6-Phosphatase (ER)

98
Q

How is pyruvate converted to phosphoenolpyruvate (PEP) in (1st 2 steps) gluconeogenesis?

A

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

99
Q

Why can gluconeogenesis not just be glycolysis in reverse?

A

Need to overcome 3 irreversible steps:
1) Pyruvate → PEP
2) Fructose 1, 6-P2 → F-6-P
3) G-6-P → Glucose

100
Q

Which enzyme is required for exporting glucose our of the cell?

A

Glucose-6-Phosphatase

101
Q

True or false.
Gluconeogenesis is thermodynamically favorable.

A

True
ΔG= -48kJ/Mol
vs reverse glycolysis= 84kJ/mol

102
Q

What are 3 substrates for gluconeogenesis?

A

1) Pyruvate
- lactate
- alanine
- other amino acids

2) Oxaloacetate
- glutamine
- other amino acids

3) Glycerol-3-P
- Glycerol

103
Q

What is the Cori cycle?

A

Lactate from RBC and muscles
→ transported to liver
→ generate pyruvate via lactate DH
→ Glucose
→ exported back to muscles and blood

104
Q

How is gluconeogenesis regulated?

A

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

105
Q

What is the pathogenesis of Glucose-6-phosphatase deficiency?

A

Genetic Glucose-6-phosphatase deficiency
↑G-6-P
1) → HMP shunt → ↑nucleotide metab → ↑uric acid

2) ↑ Glycogen → organomegaly

3) → ↑Pyruvate → ↑lactate

106
Q

What is the pathogenesis of Pyruvate carboxylase deficiency?

A

↑pyruvate
→ ↑lactate
→ ↑Acetyl-CoA
→ ↓Oxaloacetate → ↓TCA → ↓ATP

107
Q

Muscle glycogen provides short term energy during _______ while liver glycogen provides it during _______________.

A

Muscle: exercise

Liver: fasting

108
Q

Which organ contains the most amount of glycogen?

A

Muscle

109
Q

What is the major regulation point for glycogen synthesis?

A

Lengthening of glycogen primer by α-1,4-linkages by glycogen synthase

110
Q

Branching of glycogen molecules is done by establishing __________ linkages and have 2 benefits: ______________________.

A

α-1,6 linkages

Branching:
↑Sites for synthesis/degradation
↑solubility

111
Q

What is the major regulation point for glycogen breakdown?

A

Release of G-1-P by cleavage of α-1,4 linkages by glycogen phosphorylase

(diff isoforms → tissue-specific regulation)

112
Q

Other than glycogen phosphorylase, what other enzyme releases of G-1-P by cleavage of α-1,4 linkages?

A

Lysosomal α-1,4-glucosidase (1-3%)

113
Q

Describe the allosteric regulation of glycogen metabolism in the liver in a fed state.

A

Fed state:
a) ↑ glucose ↑ G-6-P ↑ATP
→ inhibit Glycogen phosphorylase
→ ↓glycogenolysis

b) ↑ G-6-P → activate glycogen synthase
→ ↑glycogenesis

114
Q

Describe the allosteric regulation of glycogen metabolism in the liver in a fasted state.

A

Fed state:
↓glucose ↓G-6-P ↓ATP
→ no inhibition of Glycogen phosphorylase
→ ↑glycogenolysis

→ ↑G-1-P → ↑UDP → inhibit glycogen synthase
→ ↓glycogenesis

115
Q

Describe the allosteric regulation of glycogen metabolism in the muscle in a active state.

A

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

116
Q

Describe the allosteric regulation of glycogen metabolism in the muscle in a resting state.

A

Low energy need:
a) ↑ ATP ↑G-6-P
→ inhibit Glycogen phosphorylase
→ ↓glycogenolysis

b) ↑ G-6-P → activate glycogen synthase
→ ↑glycogenesis

117
Q

How does insulin regulate glycogen metabolism?

A

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

118
Q

True or false:
Glucagon and epinephrine both act on both liver and muscle tissue to induce glycogenolysis and inhibit glycogenesis.

A

False
Glucagon → ONLY Liver
Epinephrine → Liver and muscle

119
Q

How does glucagon and epinephrine regulate glycogen metabolism?

A

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

120
Q

What type of glycogen storage disease, enzyme and organ affected for:
- Fasting hypoglycemia
- Organomegaly
- ↑lactate/uric acid

A

Type I (Von Gierke)
- Glucose -6-Phosphatase
- Liver and kidney affected

121
Q

What type of glycogen storage disease, enzyme and organ affected for:
- Myopathy
- Cardiac Failure

A

Type II (Pompe)
- 1-4 Glucosidase (minor enzyme → no hypoglycemia)
- General (lysosomal) affected

122
Q

What type of glycogen storage disease, enzyme and organ affected for:
- Fasting hypoglycemia
- Hepatomegaly
- Muscle weakness

A

Type III (Cori)
- 4-4 transferase and/or 1-6 glucosidase
- Liver, muscle, heart affected

123
Q

What type of glycogen storage disease, enzyme and organ affected for:
- Hepatosplenomegaly
- Early Death

A

Type IV (Andersen)
- Branching enzyme
- Liver

124
Q

What type of glycogen storage disease, enzyme and organ affected for:
- Exercise-induced muscle pain
- Cramps

A

Type V (McArdle)
- Muscle glycogen phosphorylase
- skeletal muscle

Metabolism and Biochem (8 decks)

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