Metabolism of Carbohydrates and Lipids Flashcards

1
Q

Inhibitors of Complex I (NADH dehydrogenase)

A

Barbiturate
Piericidin A
Amytal
Rotenone

MNEMONIC: RotenONE acts on complex ONE

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2
Q

Inhibits of Complex II (succinate dehydrogenase)

A

Malonate
Carboxin
TTFA

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3
Q

Inhibitors of Complex III (ubiquinol:ferricytochrome oxidoreductase)

A

Antimycin A

Dimercaprol

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4
Q

Inhibitors of Complex IV (cytochrome oxidase)

A

Cyanide
Carbon monoxide
Sodium azide
Hydrogen sulfide

MNEMONIC: CO blocks CO
Carbon monoxide blocks Cytochrome Oxidase

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5
Q

Three examples of uncouplers

A

2,4-dinitrophenol
Aspirin
Thermogenin

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6
Q

Complex V (ATP synthase) inhibitor

A

Oligomycin

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7
Q

Rate limiting step

Glycosis

A

Phosphofructokinase

Fructose-6-phosphate –> Fructose-1,6-biphosphate

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8
Q

Hexokinase or glucokinase

  1. Acts at a constant rate to provide glucose-6-phosphate to meet the cell’s need
  2. High Km
  3. Activity induced by insulin
  4. Present in most tissues
  5. High Vmax
A
  1. Hexokinase
  2. Glucokinase
  3. Glucokinase
  4. Hexokinase
  5. Glucokinase
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9
Q

The transport of reducing equivalents (NADH) from the cytosol to the mitochondria requires this enzyme. It reduces ___ to ___ which then traverse the mitochondrial membrane.

A

Malate dehydrogenase reduces oxaloacetate to malate, which crosses the mitochondrial membrane from the cytosol to matrix.

In the mitochondrion, oxaloacetate is deaminated to aspartate. In the process glutamate is ‘aminated’ to form a-ketoglutarate. A-KG and Asp then traverses the membrane from the matrix to the cytosol to form oxaloacetate and glutamate. Cycle repeats.

(Malate-Aspartate shuttle)

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10
Q

Reducing equivalents are produced at which step of glycolysis

A

Glyceraldehyde-3-phosphate -> 1.3-biphosphoglycerate

Glyceraldehyde phosphate dehydrogenase

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11
Q

These organs are strictly glycolytic. The major fate of pyruvate in these organs is to be converted into lactate by lactate dehydrogenase.

A
  1. RBC
  2. Lens
  3. Cornea
  4. Kidney (medulla)
  5. Testes
  6. WBC
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12
Q

In the human body, pyruvate can participate in:

A. Anaerobic glycolysis, in which it is converted to ___ by ____ (enzyme).
B. Gluconeogenesis, in which it is converted to ___ by ____ (enzyme).
C. TCA, in which it is converted to ___ by ___ (enzyme).

A

A. Lactic acid, lactate dehydrogenase
B. Oxaloacetate, pyruvate carboxylase
C. Acetyl CoA, pyruvate dehydrogenase

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13
Q

Pyruvate dehydrogenase requires 5-coenzymes:

A
  1. Lipoic acid
  2. NAD+
  3. FAD
  4. Thiamine pyrophosphate
  5. Coenzyme A
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14
Q

In skeletal muscle, glycogen rather than glucose is used for anaerobic glycolysis. Why?

A

Glycogen can be ‘broken down’ by glycogen phosphorylase to glucose-1-phosphate, which is interconvertible with glucose-6-phosphate. This saves muscle 1 ATP that would otherwise be used by hexokinase (to convert glucose to glucose-6-phosphate). This increases the net yield of ATP from 2 to 3 ATPs per glucose molecule undergoing anaerobic glycolysis.

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15
Q

Why are alcoholics thiamin-deficient?

A

2 reasons.

  1. Poor intake
  2. Alcohol inhibits thiamine absorption
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16
Q

Oxidation of glucose yields up to ___ ATP under aerobic conditions, but only ___ ATP when oxygen is absent.

A

Aerobic conditions: 38 (or 36)

Anaerobic: 2

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17
Q

When blood samples are taken for measurement of glucose, it is collected in tubes containing FLUORIDE to inhibit glycolysis. Fluoride is an inhibitor of this enzyme.

A

Enolase

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18
Q

Arsenic poisoning occurs because it reacts with the ____ component of ___.

A

-SH groups of lipoic acid
Lipoic acid is a cofactor of:
1. Pyruvate dehydrogenase
2. Alpha-ketoglutarate dehydrogenase

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19
Q

Products of glycolysis per glucose molecule.

A

2 ATPs

2 NADH

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20
Q

3 irreversible and regulated steps in glycolysis

A
  1. Phosphorylation of glucose
  2. Phosphorylation of fructose-6-phosphate
  3. Formation of pyruvate
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21
Q

2 glycolytic reactions in which substrate level phosphorylation occurred

A
  1. Formation of pyruvate

2. Formation of 3-phosphoglycerate

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22
Q

Fluoroacetate is toxic because it inhibits which enzyme of the citric acid cycle.

A

Fluoroacetate condenses with oxaloacetate to form fluorocitrate which inhibits ACONITASE.

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23
Q

CO2 is released at which steps in the TCA cycle.

A

Isocitrate > a-KG (Isocitrate dehydrogenase)

a-KG > Succinyl-CoA (a-KG dehydrogenase)

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24
Q

Decarboxylation reactions in TCA require which two cations

A

Mn++

Mg++

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25
Q

GTP is produced at which step of the TCA cycle

A

Succinyl-CoA > Succinate (Succinate thiokinase)

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26
Q

Reducing equivalents are released at which steps of the TCA cycle.

A

NADH (3)

  1. Isocitrate > a-KG (Isocitrate dehydrogenase)
  2. a-KG > Succinyl-CoA (a-KG dehydrogenase)
  3. Malate > Oxaloacetate (malate dehydrogenase)

FADH2 (1)
Succinate > Fumarate (Succinate dehydrogenase)

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27
Q

In tissues capable of gluconeogenesis, the GTP produced in the TCA cycle is used in:

A

Decarboxylation of oxaloacetate to PEP in gluconeogenesis. This effectively withdraws oxaloacetate from TCA into gluconeogenesis.

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28
Q

Which enzyme in the TCA is also a part of the ETC?

A

Succinate dehydrogenase (Complex II)

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29
Q

How many ATPs are formed per turn of the TCA cycle?

A

3 NADH x 3 = 9 ATPs
1 FADH2 x 2 = 2 ATPs
1 GTP
= 12

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30
Q

Is the TCA catabolic or anabolic?

A

Both. It is amphibolic.

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31
Q

The key enzyme that catalyzes the net transfer out of the TCA into gluconeogenesis

A

Phosphoenolpyruvate carboxykinase.
Catalyzes oxaloacetate > PEP > Glucose.
GTP used in this reaction

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32
Q

The most important reaction that catalyzes net transfer into TCA cycle.

A

Carboxylation of pyruvate to form oxaloacetate.

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33
Q

Is acetyl-CoA inhibitory/stimulatory to:
A. Pyruvate dehydrogenase
B. Pyruvate carboxylase

A

A. Inhibitory

B. Stimulatory. Ensures steady supply of oxaloacetate for condensation with acetyl-CoA.

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34
Q

Which keto-acids are formed by the following amino acids after transamination reactions?

A. Alanine
B. Asparate
C. Glutamate

A

A. Pyruvate
B. Oxaloacetate
C. Alpha-ketoglutarate

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35
Q

Acetyl-CoA is the major substrate for long chain fatty acid synthesis, which occurs in the cytosol. But pyruvate dehydrogenase which produces Acetyl-CoA is a mitochondrial enzyme. How is Acetyl-CoA made available in the cytosol given that it is impermeable to the mitochondrial membrane?

A

Acetyl-Coa condenses with oxaloacetate to form citrate (TCA). It is citrate that is transported into the cytosol, and cleaved by ATP-CITRATE LYASE. Citrate is only available for transport out of the mitochondrion when aconitase is saturated with its substrate.

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36
Q

The dehydrogenases in TCA is activated by ___ which increases in concentration during muscular contraction.

A

Ca++

37
Q

Rate-limiting step!

TCA

A

Isocitrate > alpha-ketoglutarate

Isocitrate dehydrogenase

38
Q

This intermediate of the TCA cycle is important in heme synthesis

A

Succinyl-CoA

39
Q

In the TCA, only a small quantity of ___ is needed for the oxidation of large quantity of acetyl-CoA; it can thus be considered as playing a catalytic role.

A

Oxaloacetate

40
Q

3 biochemical pathways that occur both in the mitochondria and the cytosol

A

Heme synthesis
Urea cycle
Gluconeogenesis

41
Q

These enzymes in gluconeogenesis reverse non-equilibrium reactions in glycolysis.

A
  1. Pyruvate > PEP
    A. Pyruvate carboxylase
    B. PEP carboxykinase
  2. Fructose-1,6-biphosphate > F-6-P
    Fructose-1,6-biphosphatase
  3. G6P > Glucose
    Glucose-6-phosphatase
42
Q

Fructose-2,6-biphosphate is an allosteric regulator of many enzymes. What is its effect on:
A. Phosphofructokinase-1
B. Fructose-1,6-biphosphatase

A

A. Stimulates

B. Inhibits

43
Q

Biotin is a cofactor in carboxylation reactions. Enumerate three carboxylation reactions.

A
  1. Pyruvate > Oxaloacetate
  2. Acetyl CoA > Malonyl CoA
  3. Propionyl CoA > Succinyl CoA
44
Q

Glucose transporter quiz

  1. Active uptake of glucose against a concentration gradient
  2. Found in the brain, kidney and placenta
  3. Found in erythrocytes
  4. Insulin-stimulated uptake
  5. Apical membrane of enterocytes
  6. Rapid uptake of glucose (liver, pancreas)
A
  1. SGLT1
  2. GLUT3
  3. GLUT1
  4. GLUT4
  5. GLUT5
  6. GLUT2
45
Q

Renal threshold for glucose

A

9.5 - 10 mmol/L

46
Q

Energy expenditure of gluconeogenesis

A

4 ATP
2 GTP
2 NADH

47
Q

Rate limiting step!

Glycogenesis

A

Elongation of glycogen chains

Glycogen synthase

48
Q

Rate limiting step!

Glycogenolysis

A

Removal of glucose

Glycogen phosphorylase

49
Q

The lack of this enzyme in the pentose phosphate pathway in primates explains why ascorbic acid is a dietary requirement for humans.

A

Gulonolactone oxidase

50
Q

What is the key enzyme in the oxidative phase of PPP? What are the main products

A

Glucose-6-phosphate dehydrogenase
NADPH
Ribulose-5-phosphate

51
Q

Source of glucoronate for reactions involving its incorporatio into proteoglycans or for reactions of substrates

A

UDP-glucuronate

52
Q

How does a high fructose diet cause hypertriacylglycerolemia, hypercholesterolemia and hyperuricemia?

A

Fructose undergoes more rapid glycolysis in the liver than does glucose; flooding the pathways in the liver leading to enhanced fatty acid synthesis, increased esterification of fatty acids, and increased VLDL.

53
Q

3 enzymes that act in fructose catabolism.

A

Fructokinase - forms Fructose-1-phosphate
Aldolase B - cleaves F1P into D-glyceraldehyde and DHAP
Triokinase - phosphorylates D-glyceraldehyde into glyceraldehyde-3-phosphate

54
Q

What are insulin-insensitive structures, i.e., they do NOT require insulin for glucose uptake?

A
Lens
Retina
Schwann cells
Liver
Kidney
Placenta
RBC
Ovaries
Seminal vesicles

Contain aldose reductase which converts glucose to sorbitol

55
Q

This enzyme is found in seminal vesicles to synthesize the substance that provides the fuel for sperm

A

Sorbitol dehydrogenase

Sorbitol > Fructose

56
Q

Rate limiting step!

Fatty acid synthesis

A

Carboxylation of Acetyl-CoA to malonyl-CoA

Acetyl-CoA carboxylase

57
Q

Elongation of very long fatty acids occur in ___ while b-oxidation of very long fatty acids occur in ___.

A

Endoplasmic reticulum = Elongation

Peroxisome

58
Q

Rate limiting step!

Beta oxidation

A

Fatty acyl CoA + carnitine > Fatty acylcarnitine + CoA

Carnitine acyltransferase

59
Q

Before fatty acids can be used for metabolism, describe the reaction that has to occur.

A

Activation by fatty acyl-CoA synthetase

Fatty acid + CoA + ATP > Fatty acyl CoA + AMP + PPi

Requires 2 ATP equivalents

60
Q

An example of a “suicide enzyme”

A

Cyclooxygenase capable of self-catalyzed destruction

61
Q

Rate-limiting step!

Bile acid synthesis

A

Cholesterol-7-a-hydroxylase

62
Q

Rate-limiting step!

Steroid hormone synthesis

A

Conversion of cholesterol to pregnenolone by desmolase (inhibited by aminogluthetimide)

63
Q

Farnesyl pyrophosphate is an intermediate in the pathway used for the synthesis of:

A

Coenzyme Q
Dolichol pyrophosphate
Prenylation of proteins
Heme A

64
Q

Major apolipoprotein of HDL

A

Apo A

65
Q

Major apolipoprotein of LDL

A

Apo B-100

66
Q

Major apolipoprotein of chylomicrons

A

Apo B-48

67
Q

Where is Apo B100 synthesized? B-48?

A

B-100 is synthesized in the liver.
B-48 is synthesized in the small intestine.

Remember that B-48 is incorporated into chylomicrons which transport fat from the small intestine to the liver.

68
Q

Some apolipoproteins function as enzyme cofactors. Which is the co-factor of:

A. Lipoprotein lipase
B. Lecithin:cholesterol acyltransferase

A

A. C-II

B. A-I

69
Q

This apolipoprotein is believed to be important in human neurodegenerative disorders.

A

Apo D

70
Q

These apolipoproteins act as ligands for the LDL receptor.

A

Apo E

Apo B-100

71
Q

Some apolipoproteins are enzyme inhibits. Which inhibit:

A. Lipoprotein lipase
B. Cholesteryl ester transfer protein

A

A. C-III, A-II

B. C-I

72
Q

2 proteins important in uptake of free fatty acids in peripheral tissues

A

Membrane fatty acid transport protein: transmembrane co-transporter with Na

Fatty acid binding protein: binds free fatty acids within the cytosol

73
Q

The vehicles of transport of triacylglycerol from the liver to the extrahepatic tissues

A

VLDL

74
Q

This apolipoprotein is essential for chylomicron and VLDL formation. Lack of lipoprotein leads to formation of lipid droplets in intestine and liver.

A

Apo B

Abetalipoproteinemia

75
Q

Newly secreted (nascent) chylomicrons and VLDL contain only a small amount of apoC and apoE. The full complement is acquired from ____ in the circulation.

A

HDL

76
Q

T/F. Insulin enhances lipoprotein lipase synthesis in adipocytes and its translocation to the luminal surface of the capillary endothelium.

A

True. Upregulation of lipoprotein lipase leads to uptake of fatty acids by adipocytes from VLDL, chylomicrons.

77
Q

This receptor plays an important part in delivery of fatty acids from VLDL TAG to adipocytes.

A

VLDL receptor

78
Q

Uptake of chylomicron remnants in the lier is mediated by ___

A

Apo E

79
Q

In uptake, Apo E in chylomicrons interact with ___ and ___ in the liver.

A
  1. LDL receptor (Apo B-100, Apo E)

2. LRP (LDL-receptor-related protein)

80
Q

Where is HDL synthesized?

A

Both liver and intestine.

However, apo C and apo E are synthesized only in the liver; and transferre to intestinal HDL in plasma.

81
Q

How can starvation cause the formation of a fatty liver?

A

In starvation, low insulin and high glucagon increases lipolysis. Increasing influx and esterification of free fatty acids in the liver outpace production of VLDL and cause fatty liver.

82
Q

This causes fatty liver by interfering with glycosylation of VLDL, inhibiting its release. it is also believed to impair recruitment of TAG to particles.

A

Orotic acid

83
Q

This ‘lipotropic factor’ important in phospholipid synthesis is lacking in many forms of fatty liver.

A

Choline

84
Q

Hormone sensitive lipase is sensitive to which hormones.

A
GLUCAGON
Epinephrine
Norepinephrine
ACTH
MSH
TSH
GH
Vasopressin
85
Q

The activity of cholesterol 7a-hydroxylase in bile acid synthesis is suppressed by ___ which is activated when the size of the bile acid pool increases.

A

Farnesoid X receptor

86
Q

Which secondary bile acid is particularly important in activating farnesoid X receptor?

A

Chenodeoxycholic acid

87
Q

How does PUFA lower cholesterol levels?

A

Up-regulation of LDL receptors increasing the catabolic rate of LDL - the main atherogenic lipoprotein

88
Q

How does alcohol raise HDL levels?

A

Increased synthesis of Apo-A1

Changes in activity of cholesteryl ester transfer protein