Ch 9 - Carbohydrate Metabolism Flashcards

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1
Q

GLUT 2

A
  • occus in cytoplasm
  • a glucose transporter
  • low affinity transporter
  • hepatocytes and pancreatic cells
  • high Km
  • liver picks up excess glucose (when glucose conc is high)
  • can be sensor for insulin release
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2
Q

GLUT 4

A
  • adipose tissue and muscle
  • respond to peripheral glucose level
  • insulin stimulates GLUT 4 transporters to the surface of the cell via exocytosis
  • Km 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
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3
Q

glycolysis overview

A
  • 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
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4
Q

Hexokinase

A
  • 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
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5
Q

Rate limiting enzymes

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

Phosphofructokinases

A
  • 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
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7
Q

Phosphofructokinase-2

A
  • 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
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8
Q

Glyceraldehyde-3-phosphate dehydrogenase

A
  • catalyze oxidation and add phosphate to glyceraldehyde 3-P
  • 1,3 bisphosphoglycerate produced
  • reduce NAD+ to NADH
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9
Q

3-phosphoglycerate kinase

A
  • 1,3 bisphosphoglycerate to ADP
  • produce ATP and 3-phosphoglycerate
  • substrate level phosphorylation
    • does not require oxygen
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10
Q

Pyruvate kinase

A
  • 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
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11
Q

Fermentation

A
  • absence of oxygen
  • lactate dehydrogenase
    • oxidize NADH to NAD+
    • reduce pyruvate to lactate
    • produce NAD+ to be used in glycolysis
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12
Q
A
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13
Q

DHAP

A
  • Dihydroxyacetone phosphate
  • hepatic and adipose triacylglycerol synthesis
  • intermediate in glycolysis
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14
Q

1,3 - BPG

A
  • 1,3 bisphosphoglycerate
  • PEP (phosphoenolpyruvate)
  • Both high energy intermediates used to generate ATP by substrate level phosphorylation
    • only ATP generated in anaerobic respiration
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15
Q

Irreversible enzymes og glycolysis

A
  • keep moving in one direction
  • hexokinase and glucokinase
  • PFK-1
  • pyruvate kinase
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16
Q

Glycolysis in erythrocytes

A
  • 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
17
Q

Galactose metabolism

A
  • 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
18
Q

fructose metabolism

A
  • part of sucrose
  • fructokinase
  • cleaved into glyceraldehyde and DHAP by aldolase
19
Q

pyruvate dehydrogenase

A
  • 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
20
Q

Glycogen

A
  • stored in liver and muscle cells
  • branched allows for faster access
  • stored in glycogen granules in cytoplasm
  • made of glucose
21
Q

Glycogenesis

A
  • 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
22
Q

branching enzyme (glycogenesis)

A
  • 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
23
Q

Glycogenolysis

A
  • 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
24
Q

Debranching enzyme (glycogenolysis)

A
  • 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
25
Q

Gluconeogenesis

A
  • 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
26
Q

Pentose phosphate pathway

A
  • 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
27
Q

Enzymes of gluconeogenesis

A
  • 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
28
Q

NADPH

A
  • electron donor, reducing agent
  • used for biosynthesis
  • prevents oxidative damage
    • accomplished via glutathione
      • reducing agent that reverses radical formation
29
Q

location of processes

A
  • 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