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BIOCHEMISTRY > ME03 - GLYCOGEN METABOLISM > Flashcards

ME03 - GLYCOGEN METABOLISM Flashcards

1
Q

BASIC INFO FOR GLYCOGEN

A

Major storage carbohydrate in animals Branched polymer of α-D-glucose ~400g of glycogen:
1%–2% of the fresh weight of resting muscle ~100g of glycogen:
10% of the fresh weight of a well-fed adult liver

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2
Q

Structure of Glycogen

A

branched-chain polysaccharide made exclusively from α-D-glucose

primary glycosidic bond is an α(1→4) linkage

After an average of eight to ten glucosyl residues, there is a branch containing an α(1→6) linkage

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3
Q

Difference between α(1-4) and α(1-6)

A

α(1-4) linkage: primary bond, about 8-10 glucose residues

α(1-6) linkage: branching bond

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4
Q

Synthesis of new glycogen molecules from α-D- glucose
Occurs in the liver and the muscle
Occurs in the cytosol

A

Glycogenesis

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5
Q

Substrates for Glycogenesis

A

SUBSTRATES:

  1. UDP-glucose
  2. ATP and UTP
  3. glycogenin: a core, primer protein
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6
Q

Product of Glycogenesis

A

Glycogen

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7
Q

Rate-limiting Step

A

Enzyme: glycogen synthase
Reaction: elongation of glycogen, i.e., addition of α(1-4) bonds

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8
Q

STEPS

A
  1. Glucose-6-P to Glucose-1-P
    → Enzyme: phosphoglucomutase
    → This is a reversible process and is not rate- limiting
  2. Synthesis of UDP-Glucose
    → Enzyme: UDP-glucose phosphorylase
    → Substrates: glucose-1-P and UTP
  3. Elongation of glycogen chains
    → The rate-limiting step of glycogenesis
    → Enzyme: glycogen synthase
    → Forms α(1-4) bonds between glucose residues
    → Bonds formed at the non-reducing end (i.e., carbon 4)
  4. Formation of branches in glycogen
    → Enzyme: branching enzyme composed of amylo α(1-4) -> α(1-6) transglucosidase
    → Forms new α(1-6) bonds by transferring 5 to 8 glucosyl residues
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9
Q

Degradative pathway that mobilizes stored glycogen in liver and skeletal muscle. Shortening of glycogen chains to produce moleculesofα-D-glucose
Also occurs in the cytosol.

A

GLYCOGENOLYSIS

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10
Q

Substrate, Product and Rate-limiting Step of Glycogenolysis

A

SUBSTRATE: Glycogen
→ Leaves about 4 glucose residues before a branch point called limit dextrin

PRODUCTS: Glucose-1-P and Free glucose
Liver: can release free glucose to circulation
Muscle: limited to glucose-6-P within muscle only
Free glucose is a product of the debranching process

RATE-LIMITING STEP:
→ Reaction: removal of glucose (breaks
a(1→4) bonds)
→ Enzyme: glycogen phosphorylase

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11
Q

STEPS IN GLYCOGENOLYSIS

A

Removal of Branches
Conversion of Glucose 1P to Glucose 6P
Lysosomal Degradation of Glycogen

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12
Q

Removal of Branches

A 
→ Enzymes: debranching enzyme
composed of
❖ α(1→4) α(1→4)
glucantransferase
➢ transfers a trisaccharide
unit from one branch to the other, exposing the 1 → 6 branch point
❖ amylo-α(1→6) glucosidase
➢ catalyzes hydrolysis of the 1
→ 6 glycoside
➢ bond to liberate free glucose
→ Bonds cleaved: α(1→4) and α(1→6)
→ Products: free glucose from the breakage
of the α(1→6) bond
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13
Q

Conversion of glucose-1-P to glucose-6-P

A

Enzyme: phosphoglucomutase
→ Liver: glucose-6-P further converted to glucose (by glucose 6-phosphatase)

❖ The glucose then is transported from the ER to the cytosol. Hepatocytes release glycogen-derived glucose into the blood to help maintain blood glucose levels until the gluconeogenic pathway is actively producing glucose
→ Muscle: glucose-6-P is the final product

❖ In the muscle, glucose 6- phosphate Cannot be
dephosphorylated and sent into the blood because of a lack of glucose 6-phosphatase. Instead, it enters glycolysis, providing energy needed for muscle contraction


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14
Q

Lysosomal degradation of glycogen

A

Enzyme:α(1→4) glucosidase

❖ Also known as acid maltase, an enzyme that is different from glycogen phosphorylase.

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15
Q

Group of inherited disorders characterised by deposition of an abnormal type or quantity of glycogen in the tissues

→ Abnormal glycogen metabolism
→ Accumulation of glycogen within cells

A

Glycogen Storage Diseases

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16
Q

Types of Glycogen Storage Diseases

A 
I - Von Gierke's | Def in G6Phosphatase 
II - Pompe's | Def in acid maltase
III - Cori's - Debranching enzyme
IV - Andersen's | Branching enzyme
V - McArdle's | skeletal muscle glycogen phosphorylase
VI - Hers' | hepatic glycogen phosphorylase
VII - Tarul's | Deficiency in PFK
VIII - Hepatic Phosphorylase Kinase
17
Q

Blood Glucose Level

A
  • After a carbohydrate meal = 6.5 – 7.2 mmol/L
  • Post-absorptive state = 4.5 – 5.5 mmol/L
  • Fasting = 3.3 – 3.9 mmol/L
18
Q

Sources of BLOOD GLUCOSE

A
  1. From carbohydrates in diet
  2. From glucogenic Compounds that undergo gluconeogenesis
  3. From liver glycogen by glycogenolysis
19
Q

Known as the Lactic acid cycle. It is a metabolic pathway in carbohydrate metabolism that links anaerobic glycolysis in muscle tissue to gluconeogenesis in the liver.

A

Cori Cycle

20
Q

Metabolic Mechanisms for Blood Glucose Regulation

A
  1. Liver
    • Regulate blood glucose after a meal through glucokinase activity
    • Freely permeable to glucose which is then phosphorylated by glucokinase (in direct contrast to extrahepatic cells which are relatively impermeable to glucose but on entry is phosphorylated by hexokinase)
  2. Kidneys
    • → → •
    Glucose filtered by glomeruli but reabsorbed by renal tubule
    Renal threshold for glucose = 9.5 – 10 mmol/L
    Reabsorption rate = 350 mg/min –
    When glomerular filtrate contains more glucose than can be reabsorbed →GLYCOSURIA →may indicate Diabetes Mellitus
21
Q

In Hormonal Control

A

Insulin

22
Q

Insulin

A

Produced by b cells of islet of Langerhans in pancreas

23
Q

Produced by A cells of islet of Langerhans Stimulated by hypoglycemia
→ Increases glycogenolysis and gluconeogenesis

A

Glucagon

24
Q 
Elevates blood glucose
→ Antagonize action of insulin
→ Decreases glucose uptake in certain
tissues, e.g. muscles
→ Mobilizes free fatty acid from adipose
tissues
A

Anterior Pituitary Hormones (GH, ACTH)

25
Q

→ Secreted by adrenal cortex
→ Increases gluconeogenesis
→ Decreases utilization of glucose in
extrahepatic tissues

A

Glucocorticoid

26
Q

Secreted by adrenal medulla

→ Increases glycogenolysis in liver and muscles

A

Epinephrine

27
Q

Diabetogenic action → FBS elevated in hyperthyroidism

A

Thyroid muscle

28
Q

Types of Diabetes Mellitus

A

Type I - Insulin is absent or deficient because the pancreas lacks or has defective b-cells
Type II - Deficiency of insulin receptors; insulin level is normal or may be elevated

29
Q

Glucose entry into cells is impaired →HYPERGLYCEMIA
• Blood glucose levels become so elevated that the glucose “spills over” into the urine → GLYCOSURIA
• Gluconeogenesis, triacylglycerol hydrolysis, fatty acid oxidation and ketone bodies formation are accelerated → KETOACIDOSIS

A

Marks & Spencer

BIOCHEMISTRY (25 decks)

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