Lecture 303: gluconeogenesis

Question 1

gluconeogenesis

Answer 1

• biosynthesis of glucose from non-carbohydrate substrates [pyruvate]

Question 2

g of glucose needed by entire body/ brain/ in storage

Answer 2

• body 160g
• brain needs 120g
• body has 210g glucose reserves

Question 3

where is glucose synthesized

Answer 3

• liver
• one precursor generated in mitochondria
• glucose generated in ER
• transported into cytosol [predominates here]

Question 4

3 irreversible steps of glycolysis bypassed during gluconeogenesis

Answer 4

• 2 enzymes needed for pyruvate kinase
• 1 enzyme needed for PFK-1
• 1 enzyme needed for hexokinase

Question 5

step 1

Answer 5

• bypassing pyruvate kinase
• done via pyruvate carboxylase and PEPCK
• pyruvate carboxylase REQUIRES ATP
• pyruvate carboxylase creates oxaloacetate in mitochondria = taken into cytosol via malate dehydrogenase
• PEPCK REQUIRES GTP AND IS REGULATED
• PEPCK acts in decarboxylation of oxaloacetate to PEP

Question 6

step 2

Answer 6

• PEP converted to F1,6BP via glycolytic enzymes

- entire energy investment here

Question 7

step 3

Answer 7

• bypass PFK-1 to convert F1,6BP to F6P via F1,6BPase
• most important step in gluconeogenesis
• regulated
• removes Pi group from C1

Question 8

step 4

Answer 8

• isomerize [synthesize] F6P to G6P via glycolytic enzymes

Question 9

step 5

Answer 9

• bypass glucokinase and hexokinase to convert G6P to glucose via G6Pase
• remove Pi group from C6
• in endoplasmic reticulum

Question 10

G6Pase found primarily

Answer 10

• liver
• kidney cortex
• organs that need glucose as primary carbon source DO NOT express G6Pase [can’t synthesize glucose]

Question 11

G6Pase deficiency

Answer 11

• Von Gierke Disease
• severe hypoglycemia
• enlarged liver
• growth failure, increased infection risk, impaired blood clotting, neurodevelopmental delay

Question 12

non-pyruvate starting points

Answer 12

• lactate, glutamine or alanine precursor to pyruvate
• glutamine or propionate precursor to oxaloacetate
• glycerol precursor to steps leading up to F1,6BP

Question 13

role of PEPCK in kidney cortex

Answer 13

• gluconeogenesis to detox ammonia

Question 14

role of PEPCK in adipose tissue

Answer 14

• adipose incapable of complete gluconeogenesis [lacks G6Pase]
• PEP produced by PEPCK converted to G3P [glyceroneogenesis]
• high levels of PEPCK leads to obese mice because of increased fat synthesis [inc. triacylglycerol content]

Question 15

role of PEPCK in skeletal muscle

Answer 15

• skeletal muscle incapable of complete gluconeogenesis [lacks G6Pase]
• PEPCK in high amounts led to freaky mice

Question 16

additional intermediate in gluconeogenesis NOT included in glycolysis

Answer 16

oxaloacetate

Question 17

G6Pase found in ____ and not in ____

Answer 17

• found in liver and kidney cortex

- not found in brain or muscle

Question 18

gluconeogenesis precursors

Answer 18

• lactate
• glycerol
• almost all AA especially alanine and glutamine but exception to leucine and lysine