BC 29 Glycogen Metabolism

Question 1

Purpose of Fed State metabolism pathways in liver (glycolysis, glycogenesis, lipogenesis)

Answer 1

Glycolysis: Energy for liver

Glycogenesis: clear portal blood glucose and store energy in prep for long term fasting

Lipogenesis: TA and TAg synthesis- shunting acetyl coA to fatty acyl coA (FA) and combining with glycerol P to form TAG

all three but especially 1 and 2 active concurrently, when their needs are met more is shunted to three

Question 2

Glycogen structure and location

Answer 2

primarily liver and muscle, other amounts relatively small

structure: amylopectin: glygenin core with alpha 1-4 and alpha 1-6 bonds connecting glucose chains

Question 3

Physiological significance of glycogenesis and excess

Answer 3

Clearance of high glucose after carb rich meal

• prevents hyperglycemia: GLUT2/Glucokinase and glycogenesis assist liver to celar portal blood in first pass
• insulin stimulation causes GLUT4/hexokinase and muscle glycogenesis to consume post prandial from PB
• limited storage capacity: 100g in liver, 400g in muscle, then converted to fat
• -glycogen mobilized more readily than fat
• -glycogen glucose can be broken down more readily

glycogen is mobilized more rapidly than fat

Question 4

Glycogenesis Process

3 steps, enzymes and significance

Answer 4

1. Activation-G6P converted to G1P (tagged for glycogenesis) then UDP glucose (UDP GLUCOSE PHOSPHORYLASE)
2. Polymerization- UDP glucose is added to strand by Glycogen Synthase (rate limiting) in alpha 1-4 config
3. Amylopectin Formation: Branching enzyme breaks off sxn adds it in alpha 1-6 formation and glygogen synthase adds more to BOTH strands
   - if no strands present tyrosine on GLYCOGENIN acts as starter (almost never happens bc we rarely fully deplete)

Question 5

Liver Fasting State Priorities

Answer 5

1. TAG lipolysis (for liver E)
2. TCA ETC OP
3. service- Ketogenesis -utilize surplus AcCoA for export of Ketone bodies
4. service- Glucogenolysis-catabolize for export
5. service- Gluconeogenesis- use C skeletons from AA and substrates to maintain blood glucose levels

Question 6

Timeline for maintaining blood glucose

Answer 6

draw it-slide 17

Question 7

Protein Sparing Effect

Answer 7

We have glycogen in short term fasting so we don’t have to tap our muscles for substrates via protein breakdown (no muscle catabolism) for glucose synthesis
-using liver glycoven can be lost in some GSD Glycogen storage diseases

Question 8

Glycogen significance in Liver

Answer 8

maintain blood glucose in short term fasting

between meals

prevents muscle catabolism (minimal after 30 hours)

Question 9

Glycogen significance in muslce

Answer 9

can provide Energy during early stages of exercise

anaerobic and for priming TCA cycle

NOT FOR BLOOD GLUCOSE

unaffected by short periods of fasting, moderately decreased after WEEKS

Question 10

GLycogenolysis steps

Answer 10

1 depolymerization

• GLYCOGEN PHOSPHORYALSE (RL step)- phophorolysis (co enzyme pyridoxal phosphate Vit B6) shortening of 1-4bonds to limit dextin:4 glycosyl residue
• G1P from ends

2. Debranching: alpha 1-6 removed via DEBRANCHING ENZYME-transfers 3 of 4 glycosyls to non reducing end of another chain and cleaves off last one (free glucose)
3. Conversion:
   Glucose 6 phosphatase (liver): G1P->G6P (more usable form)

-in muscle:laks G6Pase enters glycolysis with one more ATP, feeds anaerobibic glycolysis and TCA prime

Question 11

TCA prime

Answer 11

need OAA and AcCoA to start TCA and for citrate

fed: primarily glucose
fastL primarily FA ox acCoA priming

Question 12

Glycogen Metabolism In Fed state

Answer 12

Insulin activates glycogenesis and inhibits glycogenolysis

-PROTEIN PHOSPHATASE I dephosphorylates Glycogen synthase (activated) glycogen Phos Kinase (inactive) glucogen phophorylase (inactive)

Question 13

Glycogen Metabolism in fasting state

Answer 13

glucagon activates glycogenolysis and inhibits gluconeogenesis

Phosphorylates same enzymes as insulin dephos’
-Activates Protein kinase A to phosphorylate glycogen synthase (inactive) glycogen phosphorylase kinase (active) glycogen phosphorylase (active amplification)

EPI same but also BLOCKS insulin release

Question 14

Allosteric regulation of glycogen (esis/olysis)

Answer 14

OVERRRIDES hormonal for fast response

• increase G6P activates glycogenesis inhibits glycogenolysis
• increase ATP/AMP inhibit glycogenolysis (esp in muscle)
• inctease Ca2/Calmoduline from muscle contraction activates glycogenolysis (why?)