Lecture 6- CHO Metabolism

Question 1

Fate of Glucose:

Answer 1

• Enters glycogenesis for energy storage
• Enters glycolysis for energy production
• Enters hexose monophosphate shunt to generate precursors for biogenesis
Which pathway is used depends on requirements of the cell (energy or biosynthesis)

Diagram

Question 2

Glycogenesis:

Answer 2

• Muscle and liver can create and store glycogen from glucose
  
  • Only liver can release glucose back into the blood, important for maintaining glucose homeostasis
  • Glucose moves into a cell, cell converts it into G6P via hexokinase in muscle cells, and glucokinase in the liver (tricks body into thinking there isn’t glucose in the cell, allows for more glucose to be brought in)
  • Creates negative feedback in muscle cells- high amounts of G6P inhibits hexokinase, prevents further glucose molecules from being brought in
  ○ In muscle cells, once glucose enters the cell, it can’t leave (must be used for energy), so don’t want too much glucose entering
  • Can store as much glucose as you want in the liver (can be returned to the blood if needed), so negative feedback doesn’t occur
  After a meal, insulin levels are high (want to remove glucose from the blood and convert it into glycogen), encourages glycogenesis by activating glucokinase

Diagram

Question 3

Glycogenin:

Answer 3

• Enzyme that serves as a scaffold on which to attach glucose molecules to build glycogen
• Acts as a primer, attaches glucose molecules to itself, allows glycogen to form and build
• Once there are ~8 glucose molecules in the chain, glycogen synthase takes over , glycogen dissociates, binds to new glucose molecules (allows for new glycogen to form)
○ 30 000+ glucose molecules can be contained in a single glycogen store
Lots of different structures of glycogen, allows for more energy to be readily accessible

Question 4

Glycogenolysis:

Answer 4

• Breaking down glycogen reserves
• Glucagon levels are high when insulin levels are low (not eating), stimulates liver to break down glycogen and increase blood glucose
Branches made of 1,6-glycosidic bonds, debranching enzymes breaks down branches

Diagrams

Question 5

Energy Production in the Cell:

Answer 5

• Substrate level phosphorylation
○ Transfer of high energy phosphate bonds
○ Occurs in the mitochondria (Kreb’s) and cytoplasm (glycolysis)
• Oxidative Phosphorylation
Occurs in the mitochondria (ETC)

Question 6

Glycolysis:

Answer 6

• Involves glycolytic enzymes in the cytoplasm
• All life on earth performs glycolysis
• Endpoint depends on available oxygen in the cell
○ Aerobic environment-> Kreb’s
○ Anaerobic -> lactic acid synthesis
• Red blood cells are dependent on glycolysis to produce ATP
Done via substrate level phosphorylation because they don’t have mitochondria

Diagram

Question 7

Glucokinase/Hexokinase:

Answer 7

Turns glucose into glucose 6 phosphate (G6P)

Question 8

Glucagon:

Answer 8

• Has inhibitory effect on the liver
• Glucagon levels are high when blood glucose is low (needs to increase blood glucose)
• The liver is the only tissue that can return glucose into the blood, don’t want all glucose to be used in glycolysis or other tissues wouldn’t have any glucose
Glucagon inhibits phosphofructokinase, inhibits glycolysis in the liver

Question 9

Lactic acid

Answer 9

○ Pyruvate converted to lactic acid
Regenerates NAD+, allows for the first part of glycolysis to occur (producing a net of 2 ATP)

Diagram

Question 10

Ethanol

Answer 10

○ Yeast can break down pyruvate into carbon dioxide and ethanol
○ Regenerates NAD+
Basis of fermentation of making beer and wine

Diagram

Question 11

Cori Cycle:

Answer 11

• Occurs in an anaerobic state in muscle cells
• Lactate is produced, transported back into liver, where gluconeogenesis allows for the conversion of pyruvate back to glucose
• 2 molecules of lactate forms one glucose molecule, consuming 6 ATP molecules in the process
• Liver is the only tissue that can take lactate and create glucose (main spot of gluconeogenesis)
More energy is consumed than produced, can’t be maintained forever

Diagram

Question 12

Hexose Monophosphate Shun

Answer 12

• Also known as the pentose phosphate pathway
• Consists of 2 phases- oxidative and non-oxidative
• Important for producing NADPH (used for biosynthesis of fatty acids, regenerating antioxidant enzymes)
○ Very important role in dealing with oxidative stress
Creates precursors for nucleotides (pentose phosphate)

• All cells use the non-oxidative phase, but only cells performing biosynthesis will use the oxidative phase
• Oxidative shunt will be turned off once enough precursors  (NADPH) have been synthesized Nucleotide synthesis can be reached through both the non-oxidative and oxidative pathways

Diagrams

Question 13

Pyruvate Dehydrogenase:

Answer 13

• Gatekeeper to Kreb's cycle
	• Large enzyme requiring several cofactors (including 4 vitamins)
		○ Thiamine
		○ Niacin
		○ Riboflavin 
		○ Pantothenic acid
	• 2 step process
		○ Decarboxylation
		○ Dehydrogenation
Occurs twice (once per each pyruvate molecule)

Equation

Question 14

Kreb’s Cycle (TCA Cycle):

Answer 14

• Over 90% of energy in food released during TCA cycle
  
  • Common and final catabolic pathway for protein, lipid, and CHOs
  • Takes place in mitochondrial matrix
  • Oxaloacetate needed for Kreb’s cycle to occur, buildup of acetyl CoA activates Pyruvate Carboxlyase to generate oxaloacetate
  • Trans amino acids- transfer of nitrogen groups to different proteins
  Some amino acids can be created to make compounds like succinyl CoA

Pathways

Question 15

Net Energy Yield:

Answer 15

• Glycolysis generates a net energy of 2 ATP + 2 NADH= 8 ATP
• Pyruvate dehydrogenation generates 1 NADH (3 ATP) x 2 (2 pyruvate per one molecule of glucose) = 6 ATP
• Kreb’s cycle generates 3 NADH, 1 FADH2, 1 GTP (12 ATP) x 2 = 24 ATP
• Total ATP= 38 ATP
• 2 ATP required for mitochondrial import of 2 NADH produced from glycolysis
○ 38-2=36 ATP
For this class, use 38 ATP

Question 16

Gluconeogenesis:

Answer 16

• Opposite of glycolysis
• Very active in the liver
• Also occurs in the kidney during starvation
• Muscle and adipose tissues lack enzymes for gluconeogenesis
• High physical activity produces muscle lactate, which goes to the liver via the Cori cycle
• Glycolysis has key steps that are irreversible, gluconeogenesis has ways to by pass these steps
Not sustainable in the long run, uses more energy than is produced

Diagrams