Ch 9 - Carbohydrate Metabolism

Question 1

GLUT 2

Answer 1

• occus in cytoplasm
• a glucose transporter
• low affinity transporter
• hepatocytes and pancreatic cells
• high K_m
• liver picks up excess glucose (when glucose conc is high)
• can be sensor for insulin release

Question 2

GLUT 4

Answer 2

• adipose tissue and muscle
• respond to peripheral glucose level
• insulin stimulates GLUT 4 transporters to the surface of the cell via exocytosis
• K_m is close to normal glucose level in blood
  
  • transporter saturated hwne levels are higher than normal
  • increasing blood glucose will not change kinetics because of saturation (zero order kinetics)
  • Increase uptake by increasing number of transporters
• muscle stores glucose as glycogen
• adipose stores glucose as glycerol phosphate then triglycerides

Question 3

glycolysis overview

Answer 3

• glucose to (2) pyruvate molecules
• 2 substrate level phosphorylation
• 1 oxidation
• can occur aerobically or anaerobically
• used in liver to help make fatty acids from glucose

Question 4

Hexokinase

Answer 4

• kinase - phosphorylate (attach phosphate group)
• glucose to Glucose 6-P via hexokinase
• traps glucose in cell because it is no longer recognized as glucose
• hexokinase - low Km, inhibited by glucose
• glucokinase - in liver and pancreatic cells
  
  • high Km, induced by insulin in hepatocytes

Question 5

Rate limiting enzymes

Answer 5

• glycolysis - phosphofructokinase-1
• fermentation - lactate dehydrogenase
• glycogenesis - glycogen synthase
• glycogenolysis - glycogen phosphorylase
• gluconeogenesis - fructose-1, 6-bisphosphatase
• pentose phosphate pathway - glucose-6-phosphate dehydrogenase

Question 6

Phosphofructokinases

Answer 6

• PFK-1
• rate limiting for glycolysis
• fructose 6-phosphate is phosphorylated to fructose 1.6 bisphosphate
• uses ATP
• inhibited by ATP and citrate
• activated by AMP
• citrate produced in citrate cycle therefore glycolysis is not needed

Question 7

Phosphofructokinase-2

Answer 7

• PFK-2
  
  • mostly in liver
• convert fructose 6-phosphate to fructose 2,6 bisphosphate (F2,6-BP)
• F2,6-BP activates PFK 1
• PFK 2 activated by insulin
• inhibited by glucagon
  
  • lowers PFK 2 therefore lower PFK 1
• PFK-2 helps PFK 1 overcome ATP caused inhibition
  
  • continue to produce metabolites even when energy is sufficient
    
    • used for glycogen, fatty acids, storage molecules

Question 8

Glyceraldehyde-3-phosphate dehydrogenase

Answer 8

• catalyze oxidation and add phosphate to glyceraldehyde 3-P
• 1,3 bisphosphoglycerate produced
• reduce NAD+ to NADH

Question 9

3-phosphoglycerate kinase

Answer 9

• 1,3 bisphosphoglycerate to ADP
• produce ATP and 3-phosphoglycerate
• substrate level phosphorylation
  
  • does not require oxygen

Question 10

Pyruvate kinase

Answer 10

• phosphoenolpyruvate (PEP) to pyruvate
• substrate level phosphorylation (ADP to ATP)
• activated by fructose 1, 6 bisphosphate
• feed-forward activation - product of earlier reaction stimulates later reaction

Question 11

Fermentation

Answer 11

• absence of oxygen
• lactate dehydrogenase
  
  • oxidize NADH to NAD+
  • reduce pyruvate to lactate
  • produce NAD+ to be used in glycolysis

Question 13

DHAP

Answer 13

• Dihydroxyacetone phosphate
• hepatic and adipose triacylglycerol synthesis
• intermediate in glycolysis

Question 14

1,3 - BPG

Answer 14

• 1,3 bisphosphoglycerate
• PEP (phosphoenolpyruvate)
• Both high energy intermediates used to generate ATP by substrate level phosphorylation
  
  • only ATP generated in anaerobic respiration

Question 15

Irreversible enzymes og glycolysis

Answer 15

• keep moving in one direction
• hexokinase and glucokinase
• PFK-1
• pyruvate kinase

Question 16

Glycolysis in erythrocytes

Answer 16

• only way to make energy
• bisphosphoglycerate mutase makes 2,3 BPG from 1,3 BPG (from glycolysis)
• mutase - moves functional groups
• 2,3 BPG binds to hemoglobin and decreases O2 affinity
• increased 2,3 BPG shifts hemoglobin curve to the right

Question 17

Galactose metabolism

Answer 17

• comes from lactose
• galactose kinase
• galactose-1-phosphate uridyltransferase
• epimerase - enzyme that converts one sugar epimer to another
  
  • epimers - differ at exactly on chiral carbon

Question 18

fructose metabolism

Answer 18

• part of sucrose
• fructokinase
• cleaved into glyceraldehyde and DHAP by aldolase

Question 19

pyruvate dehydrogenase

Answer 19

• pyruvate to acetyl-CoA in the mitochondria
  
  • produces NADH, CO2, acetyl CoA
• Pyruvate dehydrogenase complex (PDH) reaction is irreversible
• PDH activated by insulin in liver
  
  • not responsive to anything in nervous system
• needs many cofactors and coenzymes
• inhibited by acetyl-CoA

Question 20

Glycogen

Answer 20

• stored in liver and muscle cells
• branched allows for faster access
• stored in glycogen granules in cytoplasm
• made of glucose

Question 21

Glycogenesis

Answer 21

• synthesis of glycogen granules
• glycogenin is core protein
• Glucose - glucose-6-P - Glucose-1-P - UDP-glucose - glycogen
  
  • uses UTP (uridine triphosphate)
  • glycogen synthase
    
    • rate limiting enzyme
    • form a-1,4 glycosidic bond for linear chains
  • promoted by insulin and glucose 6-P
  • inhibited by glucagon and epinephrine

Question 22

branching enzyme (glycogenesis)

Answer 22

• alpha 1,6 linked branches
• Glycosyl a-1,4:a-1,6 transferase
• branch enzyme hydrolyzes an a-1,4 bond
• transfers hydrolyzed branch and attaches it to a-1,6 bond to create branch
• glycogen synthase works on both branches

Question 23

Glycogenolysis

Answer 23

• breaking down glycogen
• glycogen phosphorylase - rate limiting enzyme
• Use phosphate to break the bond
• make glucose 1-phosphate that is converted to glucose 6-phosphate
• glycogen phosphorylase - break a1, 4 to release glucose off periphery of the granule
  
  • stops at branch points (a1, 6 bonds)
  • activated by glucagon in liver, AMP, and epinephrine
  • inhibit by ATP

Question 24

Debranching enzyme (glycogenolysis)

Answer 24

• break last a1,4 before the branch
• move that cut chain to the end of the other branch and reattach (new a1, 4)
• hydrolyze a1, 6 and release single glucose as free glucose
• normaly glucose released as glucose 1-P

Question 25

Gluconeogenesis

Answer 25

• liver maintain blood glucose level while fasting using gluconeogenesis and glycogenolysis
• controlled by acetyl-CoA - activates enzymes
  
  • acetyl-CoA is not a substrate
• promoted by glucagon and epinephrine
• inhibited by insulin
• raise blood sugar level
• substrates:
  
  • glycerol 3-P
  • lactate
  • glucogenic amino acids (alanine is important)
    
    • all except lysine and leucine
    • converted to intermediates for gluconeogenesis
  • use substrates to make pyruvate and DHAP which are intermediates used to make glucose

Question 26

Pentose phosphate pathway

Answer 26

• occurs in cytoplasm
• produce NADPH and ribose 5-P (needed for nucleotides)
• glucose-6-P dehydrogenase - rate limiting enzyme
  
  • induced by insulin
  • inhibited by products
  • produces NADPH and 6-phosphogluconate
• intermediates can feed back into glycolysis

Question 27

Enzymes of gluconeogenesis

Answer 27

• pyruvate carboxylase - produce oxaloacetate (OAA) from acetyl-CoA (from fatty acids)
• phosphoenolpyruvate carboxykinase (PEPCK) - OAA to PEP, requires GTP
• Fructose-1,6-bisphosphatase - fructose 1,6 bisphosphate to fructose 6-P
  
  • rate limiting step in gluconeogenesis
• glucose-6-phsphatase - glucose-6-P to glucose
  
  • only in the liver
  • requires beta oxidation to power the process

Question 28

NADPH

Answer 28

• electron donor, reducing agent
• used for biosynthesis
• prevents oxidative damage
  
  • accomplished via glutathione
    
    • reducing agent that reverses radical formation

Question 29

location of processes

Answer 29

• glycolysis - cytoplasm
• Pyruvate from glycolysis into mitochondria
• PDH in mitochondria
• glycogen - snythetis and degrade in liver and skeletal muscle
• glycogenesis - formed in cytoplasm
• glycogenolysis - degrade in cytoplasm
• gluconeogenesis - mitochondria or cytoplasm
  
  • kidney and liver