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Tissues > T02 - Carbohydrate Metabolism I > Flashcards

T02 - Carbohydrate Metabolism I Flashcards

1
Q

Most dietary carbohydrates are in what form?

A

starch

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2
Q

Starch comes in what three forms?

A

amylose; amylopectin (from plants); glycogen (from animals)

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3
Q

Distinguish between amylose, amylopectin, and glycogen.

A

all are polymers of glucose but have different chemical linkages and branching patterns

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4
Q

Describe the carbohydrate composition of an average/normal diet.

A

50% polysaccharides; 40% disaccharides; 10% monosaccharides

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5
Q

What is cellulose?

A

an undigestable carbohydrate

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6
Q

Where does carbohydrate digestion begin?

A

in the mouth, with amylase in the saliva

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7
Q

Where does most carbohydrate digestion occur?

A

in the small intestine

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8
Q

What is the major luminal enzyme for carbohydrate digestion in the small intestine?

A

amylase secreted from pancreas

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9
Q

What are the three possible carbohydrate products following amylase action?

A

glucose; galactose; fructose

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10
Q

(T/F) The epithelium of the GI tract can absorb mono-, di-, or polysaccharides.

A

False. It can only absorb monosaccharides, which means that disaccharides have to be further hydrolyzed.

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11
Q

Polysaccharides must be hydrolyzed into monosaccharides in order to be absorbed by the epithelium of the GI tract. What happens if a polysaccharide can’t be broken down further?

A

remain in the GI tract where they exert osmotic force, preventing proper absorption of salt and water, and likely leading to diarrhea

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12
Q

A critically important feature of absorption of substances across the epithelium is the requirement for

A

the epithelial cells to be polarized cells

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13
Q

Describe the basic architecture of the system that transports monosaccharides across the GI epithelium.

A

two-step process involving sequential actions of apical membrane protein and basolateral membrane protein

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14
Q

How are the monosaccharides glucose and galactose transported across the GI epithelium?

A

transported across apical surface by sodium-glucose-galactose transporter 1 (SGLT1) protein

transported across basolateral surface by GLUT2 through facilitated diffusion

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15
Q

Describe the properties of the sodium-glucose-galactose transporter 1 (SGLT1) protein.

A

intrinsic apical membrane protein that couples active transport of either molecule with transport of Na+ ion

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16
Q

The sodium-glucose-galactose transporter 1 (SGLT1) protein is an example of what kind of transport system?

A

SGLT1 is an example of a secondary active transport system (couples movement of one molecule, Na+, down its gradient to push another, glucose & galactose, against its gradient)

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17
Q

How is the monosaccharide fructose transported across the GI epithelium?

A

absorbed by GLUT5, a distinct apical membrane protein, through facilitated diffusion

transported across basolateral surface by GLUT2 through facilitated diffusion

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18
Q

What is the primary difference between facilitated diffusion and secondary active transport?

A

in facilitated diffusion, substances can only move down their gradients, but in secondary active transport, substances can be moved against their gradients if coupled to another molecule moving down its gradient

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19
Q

What are the two classes of glucose transporters in mammalian cells?

A

Na+-dependent cotransporter

facilitated glucose transporter

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20
Q

What are the high affinity glucose transporters?

A

GLUT-1 and GLUT-3 (low Km, 1 mM)

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21
Q

The GLUT-1 transporter is primarily found in (3)

A

erythrocytes [blood]

blood/brain barrier

cancerous cells

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22
Q

What is the significance of the GLUT-3 transporter?

A

GLUT-3 transporter allows brain to have constant glucose levels, even when blood [glucose] fluctuates

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23
Q

What is the low affinity glucose transporter?

A

GLUT2 (low affinity, Km 17 mM)

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24
Q

What does it mean for the GLUT2 transporter to be “high capacity?” How is this phenomenon important in terms of hormonal regulation?

A

rate of glucose import into liver and pancreatic beta cells is proportional to concentration of glucose in blood

allows insulin-producing pancreatic beta cells to “sense” blood levels and produce insulin accordingly

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25
Q

How is the high Km of the GLUT2 transporter important in hypoglycemic conditions?

A

high Km for glucose (low affinity) means that when blood glucose is low, it’s not imported into the liver and is instead preserved for more important organs like the brain

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26
Q

Which tissues require insulin for glucose transport?

Which tissues do not require insulin for glucose transport?

A

insulin required in muscle and fat tissue

insulin not used in liver and brain

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27
Q

What is the GLUT4 transporter?

A

insulin-dependent glucose transporter in muscle/fat tissue that translocates from cytosol to plasma membrane in response to insulin administration and facilitates uptake of glucose

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28
Q

(T/F) Glucose can be stored as fat.

A

True. It can be stored as fat in adipose tissue, with the help of the GLUT4 transporter.

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29
Q

Describe the Km of the hexokinases (I-III) for glucose.

A

low Km (0.01-0.05 mM), therefore high affinity

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30
Q

Describe the distribution of the hexokinases (I-III) in the body.

A

wide tissue distribution

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31
Q

What inhibits the hexokinases (I-III)?

A

glucose-6-phosphate (G6P) allosterically inhibits the hexokinases

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32
Q

What is another name for hexokinase IV?

A

glucokinase

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33
Q

Describe the Km of glucokinase/hexokinase IV.

A

high Km (10mM), so low affinity

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34
Q

Describe the distribution of glucokinase/hexokinase IV.

A

limited tissue distribution, primarily found in liver, islets and pituitary

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35
Q

(T/F) Glucose-6-phosphate is an inhibitor of all hexokinases.

A

False. G6P inhibits hexokinases I-III, but does not inhibit hexokinase IV.

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36
Q

The GLUT2 transporter is found in what tissues?

A

liver, pancreatic islets

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37
Q

Write out the chemical equation for glycolysis.

A
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38
Q

Draw out the steps of the glycolytic pathway. Identify the enzymes and cofactors associated with each step.

A
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39
Q

What converts pyruvate to lactate? What are the associated cofactors?

A

lactate dehydrogenase catalyzes pyruvate → lactate (a reduction)

associated: NADH → NAD+

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40
Q

How can galactose be acquired?

A

synthesized from glucose

obtained from diet (component of lactose)

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41
Q

How is galactose transported across the apical surface from the lumen to the cell?

A

by a sodium-linked transporter (analogous to the Na/glucose co-transporter)

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42
Q

What three enzymes are required for galactose utilization?

A

galactokinase

uridylyl transferase

UDP-galactose-4-epimerase

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43
Q

Describe the role of galactokinase in galactose utilization.

A

phosphorylates carbon 1 of galactose in an ATP-consuming step

44
Q

How do galactokinase and hexokinase differ?

A

galactokinase phosphorylates carbon 1 of galactose, whereas hexokinase phosphorylates carbon 6 of glucose

45
Q

Describe the role of uridylyl transferase in galactose metabolism.

A

uridylyl transferase transfers UDP group from glucose to galactose-1-P to form glucose-1-P, which can then be used in glycolysis

46
Q

Describe the role of UDP-galactose-4-epimerase in galactose metabolism.

A

interconverts UDP-glucose and UDP-galactose in an NAD+-dependent reaction

47
Q

What explains why galactose is not essential in the diet?

A

UDP-galactose-4-epimerase can readily/easily interconvert UDP-glucose and UDP-galactose

48
Q

Draw out a diagram that illustrates galactose metabolism.

A
49
Q

Hereditary deficiencies for galactose metabolism mean that galactose and galactose-1-P accumulate in blood and tissues. How do cells respond to this accumulation, and what are the clinical consequences?

A

aldolase reductase reduces galactose → galactitol

galactitol accumulate and cause damage to lens of eye (cataracts)

50
Q

Fructose is absorbed and metabolized by what tissue?

A

liver

51
Q

(T/F) Fructose is regulated by insulin.

A

False. In fact, excess fructose consumption has been hypothesized to cause insulin resistance.

52
Q

Why is fructose metabolism considered to be so “dangerous?”

A

pathway of fructose metabolism in liver bypasses PFK (conversion of F-6-P into F-1,6-bP), a key regulatory step of glycolysis

53
Q

Draw a diagram outlining fructose metabolism in muscle.

A
54
Q

Draw a diagram outlining fructose metabolism in the liver.

A
55
Q

What is essential fructosuria?

A

uncommon autosomal recessive disorder involving fructose kinase deficiency

56
Q

What are the symptoms/pathological effects of essential fructosuria?

A

no pathological effects because kidney is capable of excreting excess fructose efficiently

57
Q

What causes hereditary fructose intolerance?

A

caused by deficiency in fructose-1-phosphate aldolase

58
Q

What are the symptoms of hereditary fructose intolerance? (3)

A

nausea

vomiting

failure to grow

59
Q

Ingestion of fructose in patients with hereditary fructose intolerance results in

A

severe hypoglycemia, linked to depletion of ATP and Pi

60
Q

What is the primary fuel source of RBCs?

A

glucose

61
Q

Which two tissues are responsible for gluconeogenesis?

A

liver

kidney

62
Q

Redraw the pathway of glycolysis, showing the three distinct enzymes used for gluconeogenesis.

A
63
Q

Describe the allosteric effects of fructose-2,6-bisphosphate.

A

allosteric activator of PFK

inhibitor of fructose-1,6-bisphosphatase

64
Q

Where is glucose-6-phosphatase located in the cell?

A

lumen of ER

65
Q

Glucose-6-phosphatase is ordinarily non-specific. What gives it specificity for G6P?

A

specificity conferred by G6P translocase in ER membrane

66
Q

What is the Cori cycle?

A

conversion of glucose to 3-carbon metabolites in extrahepatic tissues, and then regeneration of glucose from these metabolites in the liver

67
Q

Draw a diagram of the Cori cycle.

A
68
Q

What is the pathway for gluconeogenesis from fatty acids? Draw out the associated pathway.

A
69
Q

What two monosaccharides make up maltose?

A

maltose = glucose + glucose

70
Q

What two monosaccharides make up sucrose?

A

sucrose = glucose + fructose

71
Q

What two monosaccharides make up lactose?

A

lactose = glucose + galactose

72
Q

How is G6P shunted into the PPP?

A

converted to 6-PG, before going into PPP

73
Q

How is G6P shunted into glycogenesis or glycogenolysis?

A

first converted to G1P before being interconverted between those two cycles

74
Q

Which molecule is considered to be at the “center” of glucose utilization?

A

G6P

75
Q

Which molecule negatively regulates hexokinase?

A

glucose-6-phosphate (i.e. its own product)

76
Q

Which molecule serves as the major decision point for entry into glycolysis?

A

fructose-6-phosphate

77
Q

Which enzyme traps glucose in the cell?

A

hexokinase

78
Q

Which enzyme activates glucose for cleavage?

A

phosphofructokinase

79
Q

Which enzyme actually splits glucose?

A

aldolase

80
Q

Which enzymes harvest the energy of glucose through oxidoreduction and phosphorylation? (5)

A

G3P hydrogenase

phosphoglycerate kinase

phosphoglycerate mutase

enolase

pyruvate kinase

81
Q

What is an alternative fate for dihydroxyacetone phosphate?

A

can feed into fat

82
Q

Write out the net chemicalequation for glycolysis.

A

glucose + 2 ADP + 2 Pi → 2 pyruvate + 2 ATP + 2 NADH + 2 H2O

83
Q

What are the four possible metabolic fates of pyruvate?

A

alanine (via transamination)

oxaloacetate (via carboxylation)

acetyl CoA (via oxidative decarboxylation)

lactate (via reduction)

84
Q

Draw a diagram illustrating the fermentation of pyruvate in anaerobic conditions.

A
85
Q

What is the function of the pyruvate dehydrogenase (PDH) enzyme?

A

converts pyruvate into acetyl CoA

86
Q

Glucose can be synthesized from most amino acids. Is this process efficient?

A

No. Amino acids are not an efficient source to produce glucose.

87
Q

Among the fatty acids, which molecule is most efficient for glucose production?

A

odd-chain fatty acids

88
Q

Describe the regulatory effects of pyruvate kinase.

A

controls glycolysis vs. gluconeogenesis to prevent futile cycle

89
Q

Describe the regulatory effects of phosphofructokinase.

A

regulates amount of energy produced

90
Q

Glucokinase/hexokinase IV is regulated by

A

positively regulated by insulin

91
Q

Hexokinase (I-III) is regulated by

A

negatively regulated by G6P

92
Q

Describe the location of glucokinase in normoglycemic and hyperglycemic conditions.

A

normal conditions = glucokinase sequestered in nucleus by GK-RP

hyperglycemic = dissociated from GK-RP and released into cytoplasm

93
Q

Which molecules negatively regulate phosphofructokinase? (3)

A

ATP (too much energy already, stop making pyruvate)

citrate (too much energy already, stop making pyruvate)

H+ (too much lactate, stop making pyruvate)

94
Q

What are the two possible states of pyruvate kinase?

A

phosphorylated inactive form

dephosphorylated active form

95
Q

What molecule allosterically activates pyruvate kinase?

A

fructose-1,6-bisphosphate

96
Q

What molecules allosterically inhibit pyruvate kinase? (2)

A

ATP

alanine

97
Q

Describe the activity of pyruvate kinase in hypo- and hyperglycemic conditions.

A

hypoglycemic = pyrvuate kinase inactive (phosphorylated by protein kinase A)

hyperglycemic = pyruvate kinase active (dephosphorylated by phosphoprotein phosphatase)

98
Q

Where in the cell is the pyruvate carboxylase enzyme located?

A

mitochondria

99
Q

PEP carboxykinase is activated by

A

CREB, a hormonal regulated transcription factor

100
Q

What enzyme serves as the rate limiting step of gluconeogenesis?

A

fructose-1,6-bisphosphatase

101
Q

What molecule activates fructose-1,6-bisphosphatase?

A

citrate

102
Q

Write out the pathway of PFK-2/FBPase-2 activity in fasting conditions.

A

Fasting → glucagon → ↑ cAMP → ↑ PKA → active FBPase-2 → ↓ Fructose-2,6-BP → inactive PFK-1 → gluconeogenesis

103
Q

Write out the pathway of PFK-2/FBPase-2 activity in fed conditions.

A

Fed → insulin → dephosphorylation → active PFK-2 → ↑ Fructose-2,6-BP → active PFK-1 → glycolysis

104
Q

Which two amino acids cannot serve as substrates for glucose production?

A

lysine

leucine

105
Q

Summarize the key (i.e. rate-determining) enzyme of glycolysis and its associated regulators.

A

PFK-1

activated by AMP and F-2,6-bP

inhibited by ATP, H+, citrate

106
Q

Summarize the key (i.e. rate-determining) enzyme of gluconeogenesis and its associated regulators.

A

F-1,6-bPase

activated by F-1,6-bP and citrate

inhibited by AMP and F-2,6-bP

Tissues (23 decks)

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