Biochem - Metabolism (Part 3) Flashcards Preview

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Flashcards in Biochem - Metabolism (Part 3) Deck (171)
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1
Q

Insulin binds to what type of receptor to activate protein phosphatase, which goes on to inactivate glycogen phosphorylase kinase and glycogen phosphorylase?

A

Tyrosine kinase

2
Q

An activated glycogen phosphorylase will begin what process?

A

Glycogenolysis

3
Q

During glycogen metabolism, glucose-1-phosphate is converted to UDP-glucose by which enzyme?

A

UDP-glucose pyrophosphorylase; UDP-glucose is the substrate for glycogen synthase

4
Q

During glucose metabolism, UDP-glucose is converted to the storage form of glycogen by which enzyme?

A

Glycogen synthase

5
Q

In which organ does glycogen undergo rapid glycogenolysis during exercise?

A

Skeletal muscle

6
Q

In which organ does glycogen undergo glycogenolysis to maintain blood sugar within an appropriate range?

A

Liver

7
Q

What type of bond is found at glycogen branch points?

A

(1,6) bonds

8
Q

What type of bond is found at side-by-side linkages of glucose in glycogen?

A

(1,4) bonds

9
Q

What enzyme creates a new branch point when assembling glycogen molecules?

A

Branching enzyme

10
Q

What enzyme digests glycogen to create a limit dextran?

A

Glycogen phosphorylase

11
Q

Once a limit dextran has been created, what enzyme is necessary for further digestion of the glycogen molecule?

A

Debranching enzyme

12
Q

Glycogen digestion in the lysosome occurs through which enzyme?

A

-1,4-glucosidase

13
Q

What molecules are the end products of glycogenolysis?

A

Glucose and Pi

14
Q

What conversion must occur for the glucose-1-phosphate produced during glycogenolysis to be converted to glucose?

A

The phosphate group has to be moved from the 1 carbon to the 6 carbon

15
Q

Which enzyme reacts with a limit dextran (four glucose residues in branched configuration) during degradation of glycogen to form glucose?

A

Debranching enzyme

16
Q

Which enzyme is responsible for the conversion of glucose-1-phosphate to glucose-6-phosphate?

A

Phosphoglucomutase

17
Q

Which enzyme degrades glycogen to glucose in the lysosome?

A

Lysosomal acid maltase (-1,4-glucosidase)

18
Q

Glycogen storage diseases involve an abnormal accumulation of toxic levels of what substance within cells?

A

Glycogen

19
Q

How many types of glycogen storage diseases are there?

A

Twelve glycogen metabolism enzyme deficiencies have been described in humans

20
Q

What is another name for glycogen storage disease type I?

A

von Gierke's disease

21
Q

A patient has severe fasting hypoglycemia, increased stores of glycogen in the liver, hepatomegaly, and elevated levels of lactate in his blood. What is the likely underlying metabolic deficiency?

A

von Gierke's disease (glycogen storage disease type I) resulting from glucose-6-phosphatase deficiency

22
Q

Glycogen storage disease type I results from a deficiency of what enzyme?

A

Glucose-6-phosphatase

23
Q

What is the prognosis for a child diagnosed with Pompe disease?

A

Early death

24
Q

Name four glycogen storage diseases.

A

Von Gierke's disease (type I), Pompe;s disease (type II), Cori's disease (type III), McArdle;s disease (type V) (remember: Very Poor Carbohydrate Metabolism)

25
Q

How can you differentiate between a patient with Cori's disease and one with von Gierke's disease using blood samples?

A

Patients with Cori's disease have normal blood lactate levels due to intact gluconeogenesis, whereas those with von Gierke's have elevated blood lactate

26
Q

What is another name for glycogen storage disease type II?

A

Pompe's disease

27
Q

In a patient with McArdle's disease, would you expect increased or decreased levels of glycogen on muscle biopsy?

A

Increased levels of glycogen, because the muscle cannot break it down

28
Q

What is another name for -1,4-glucosidase?

A

Acid maltase

29
Q

What disease is the result of a deficiency of lysosomal -1,4-glucosidase?

A

Pompe;s disease (glycogen storage disease type II)

30
Q

Pompe;s disease (glycogen storage disease type II) is associated with the enlargement of what organ?

A

The heart (remember: Pompe's trashes the Pump)

31
Q

Name three organs affected in Pompe's disease.

A

Heart, liver, muscle

32
Q

What is another name for glycogen storage disease type III?

A

Cori's disease

33
Q

What is another name for -1,6-glucosidase?

A

Debranching enzyme

34
Q

What disease is the result of a deficiency of -1,6-glucosidase?

A

Cori's disease (glycogen storage disease type III)

35
Q

What is another name for glycogen storage disease type V?

A

McArdle's disease

36
Q

What disease is the result of a deficiency of skeletal muscle glycogen phosphorylase?

A

McArdle's disease (glycogen storage disease type V)

37
Q

A patient has painful cramping and myoglobinuria associated with strenuous exercise. What is the likely underlying metabolic deficiency?

A

McArdle's disease (glycogen storage disease type V) (remember: McArdle's = Muscle)

38
Q

What bodily fluid can be used to diagnose McArdle's in a patient with severe muscle cramping after exercise?

A

A urinalysis will show myoglobinuria

39
Q

What enzyme deficiency is seen in Fabry's disease?

A

-Galactosidase A

40
Q

A patient presents with progressive neurodegeneration, hepatosplenomegaly, and a cherry-red spot on his macula. Histologic examination reveals cells containing lipid droplets, confirming a lysosomal storage disease. What are these cells called?

A

Foam cells; seen in Niemann-Pick disease

41
Q

A patient presents with peripheral neuropathy, developmental delay, and optic atrophy. Histologic examination reveals multinucleated macrophages, confirming your diagnosis of a lysosomal storage disease. What are these cells called?

A

Globoid cells; seen in Krabbe's disease

42
Q

A deficiency of the enzyme -galactosidase A leads to what disease?

A

Fabry's disease

43
Q

What substrate is accumulated in Fabry's disease?

A

Ceramide trihexoside

44
Q

What type of inheritance does Fabry's disease demonstrate?

A

X-linked recessive

45
Q

What is the appearance of the cells that may serve as histologic confirmation of Gaucher's disease?

A

Gaucher's cells are macrophages that look like crumpled tissue paper

46
Q

Name two mucopolysaccharidoses.

A

Hunter's syndrome and Hurler's syndrome

47
Q

A patient shows milder symptoms and appearance similar to Hurler's syndrome but no corneal clouding; what kind of behavior patterns do you expect?

A

Aggressive behavior; this describes Hunter's syndrome, an X-linked mucopolysaccharidosis

48
Q

A patient has peripheral neuropathy of the hands and feet, angiokeratomas of the skin, and both cardiovascular and renal disease. These characteristics are typical of which lysosomal storage disease?

A

Fabry's disease

49
Q

What substrate accumulates in a patient with a deficiency of -glucocerebrosidase?

A

Glucocerebroside; it accumulates in liver, spleen, and bone in Gaucher's disease

50
Q

Name six types of sphingolipidosis.

A

Fabry's disease, Gaucher's disease, Niemann-Pick disease, Tay-Sachs disease, Krabbe's disease, metachromatic leukodystrophy

51
Q

What substrate is accumulated in Niemann-Pick disease?

A

Sphingomyelin (remember: No man picks [Niemann-Pick] his nose with his sphinger [sphingomyelinase])

52
Q

What enzyme deficiency leads to Gaucher's disease?

A

-Glucocerebrosidase

53
Q

A child has progressive neurodegeneration, developmental delay, cherry-red spots on the macula, and lysosomes with onion skinning; he does not have hepatomegaly. These characteristics are typical of which lysosomal storage disease?

A

Tay-Sachs disease

54
Q

What is the most common lysosomal storage disorder?

A

Gaucher's disease

55
Q

A patient has developmental delay, gargoylism, airway narrowing, and corneal clouding. These characteristics are typical of which lysosomal storage disease?

A

Hurler's syndrome

56
Q

Which three lysosomal storage disorders are Ashkenazi Jews at increased risk for?

A

Tay-Sachs, Niemann-Pick, and some forms of Gaucher's disease

57
Q

What type of inheritance does Gaucher's disease demonstrate?

A

Autosomal recessive

58
Q

A patient has hepatosplenomegaly, aseptic necrosis of the femur, and abnormal macrophages on histologic examination. These characteristics are typical of which lysosomal storage disease?

A

Gaucher's disease

59
Q

What is the term for macrophages that look like crumpled tissue paper under the microscope and are associated with a lysosomal storage disease?

A

Gaucher's cells

60
Q

What enzyme deficiency leads to Niemann-Pick disease?

A

Sphingomyelinase

61
Q

A deficiency of the enzyme sphingomyelinase leads to what disease?

A

Niemann-Pick disease

62
Q

What type of inheritance does Niemann-Pick disease demonstrate?

A

Autosomal recessive

63
Q

A child has progressive neurodegeneration, hepatosplenomegaly, and a cherry-red spot on his macula. These characteristics are typical of which lysosomal storage disease?

A

Niemann-Pick disease

64
Q

What enzyme deficiency leads to Tay-Sachs disease?

A

Hexosaminidase A (remember: Tay-SaX lacks heXosaminidase)

65
Q

What substrate is accumulated in Tay-Sachs disease?

A

GM2 ganglioside

66
Q

What type of inheritance does Tay-Sachs disease demonstrate?

A

Autosomal recessive

67
Q

Name two lysosomal storage diseases that may present with a cherry-red spot on the macula.

A

Niemann-Pick disease and Tay-Sachs disease

68
Q

What enzyme deficiency leads to Krabbe's disease?

A

Galactocerebrosidase

69
Q

What substrate is accumulated in Krabbe's disease?

A

Galactocerebroside

70
Q

What type of inheritance does Krabbe's disease demonstrate?

A

Autosomal recessive

71
Q

A patient has peripheral neuropathy, developmental delay, and optic atrophy. These characteristics are typical of which lysosomal storage disease?

A

Krabbe's disease

72
Q

What enzyme deficiency leads to metachromatic leukodystrophy?

A

Arylsulfatase A

73
Q

What substrate is accumulated in metachromatic leukodystrophy?

A

Cerebroside sulfate

74
Q

What type of inheritance does metachromatic leukodystrophy demonstrate?

A

Autosomal recessive

75
Q

A patient has central and peripheral demyelination with ataxia and dementia. These characteristics are typical of which lysosomal storage disease?

A

Metachromatic leukodystrophy

76
Q

What enzyme deficiency leads to Hurler's syndrome?

A

-L-iduronidase

77
Q

What substrates accumulates in Hurler's syndrome?

A

Heparan sulfate and dermatan sulfate

78
Q

What pattern of inheritance does Hurler's syndrome demonstrate?

A

Autosomal recessive

79
Q

What enzyme deficiency leads to Hunter's syndrome?

A

Iduronate sulfatase

80
Q

What substrates are accumulated in Hunter's syndrome?

A

Heparan sulfate and dermatan sulfate

81
Q

What pattern of inheritance does Hunter's syndrome demonstrate?

A

X-linked recessive

82
Q

A patient has mild developmental delay, gargoylism, and airway obstruction but no corneal clouding. These characteristics are typical of which lysosomal storage disease?

A

Hunter's syndrome

83
Q

Name the two lysosomal storage diseases that lead to an accumulation of heparan sulfate and dermatan sulfate.

A

Hunter's syndrome and Hurler's syndrome

84
Q

Name the two lysosomal storage diseases that show x-linked recessive inheritance.

A

Fabry's disease and Hunter's syndrome

85
Q

What is the name of the shuttle that moves acetyl coenzyme A from the mitochondria to the cytoplasm to participate in fatty acid synthesis?

A

Citrate shuttle (remember: SYtrate = SYnthesis)

86
Q

The addition of carbon dioxide to acetyl coenzyme A during fatty acid synthesis yields what molecule?

A

Malonyl coenzyme A

87
Q

In acyl-CoA dehydrogenase deficiency, dicarboxylic acid levels _____ (increase/decrease) and glucose and ketone levels _____ (increase/decrease).

A

Increase; decrease

88
Q

A deficiency of which enzyme in fatty acid metabolism causes an increase in dicarboxylic acids and a decrease in glucose and ketones?

A

Acyl-CoA dehydrogenase deficiency

89
Q

What cofactor is required for the conversion of acetyl-CoA to malonyl-CoA during fatty acid synthesis?

A

Biotin; it donates the CO2 group

90
Q

Where does fatty acid degradation occur? Where are the products of degradation consumed?

A

Both occur in the mitochondrion

91
Q

What is the name of the shuttle that moves long-chain fatty acids from the cytoplasm to the mitochondria to participate in fatty acid degradation?

A

Carnitine shuttle (remember: CARnitine = CARnage of fatty acids)

92
Q

After breakdown of fatty acids, the resulting acetyl-CoA groups can be put to which uses?

A

Ketogenesis or citric acid cycle

93
Q

In which direction does the citrate shuttle move acetyl-CoA across the mitochondrial membrane?

A

From the mitochondria to the cytoplasm

94
Q

In which direction does the carnitine shuttle move fatty acids across the mitochondrial membrane?

A

From the cytoplasm to the mitochondria

95
Q

A deficiency of what substance will result in hypoketotic hypoglycemia?

A

Carnitine

96
Q

What are the clinical sequelae of carnitine deficiency?

A

Weakness, hypotonia, and hypoketotic hypoglycemia due to toxic accumulation of long-chain fatty acids

97
Q

Name two ketone bodies derived from acetyl-CoA. (These are found in individuals who have experienced prolonged starvation and diabetic ketoacidosis.)

A

Acetoacetate and -hydroxybutyrate

98
Q

In a patient with high levels of circulating ketone bodies, what does the breath smell like?

A

Acetone (a fruity odor)

99
Q

Which two precursors can be made into ketone bodies?

A

Amino acids and fatty acids

100
Q

What is the precursor molecule to acetoacetate?

A

HMG coenzyme A

101
Q

In alcoholism, the citric acid cycle is stalled due to excess NADH, causing a shunting of glucose and free fatty acids toward formation of _______ _______.

A

Ketone bodies

102
Q

Which two organs can use ketone bodies as fuel during starvation?

A

Muscle and brain

103
Q

Which ketone body cannot be detected by a urine test?

A

-Hydroxybutyrate

104
Q

A patient with a history of alcoholism presents to the emergency department intoxicated. Excess NADH and the shunting of oxaloacetate to malate may result in finding what substance in his urine?

A

Ketone bodies

105
Q

Where in the body are ketones synthesized?

A

Liver

106
Q

In which two pathological states will the body produce large amounts of ketones?

A

Starvation and ketoacidosis

107
Q

The brain can convert one ketone body into two of what type of molecule?

A

Acetyl-CoA for use in the tricarboxylic acid cycle to generate adenosine triphosphate

108
Q

1 gram protein or carbohydrate = ____ kcal

A

4

109
Q

1 gram fat = ___ kcal

A

9

110
Q

During the first three days of fasting, which four processes maintain the blood glucose level?

A

Hepatic glycogenolysis, adipocyte free fatty acid release, muscle and liver free fatty acid use (instead of glucose), and hepatic gluconeogenesis

111
Q

What molecules do skeletal muscles contribute for hepatic gluconeogenesis in order to maintain the blood glucose level?

A

Lactate and alanine

112
Q

What are the only triacylglycerol molecules that can contribute to gluconeogenesis?

A

Glycerol, propionyl-CoA (from odd-chain free fatty acids)

113
Q

Which compounds do adipose tissues contribute for hepatic gluconeogenesis in order to maintain the blood glucose level during the first three days of starvation?

A

Glycerol and propionyl-CoA (from free fatty acid metabolism)

114
Q

What two metabolic processes does the liver undergo to maintain blood glucose level in the first three days of fasting/starvation?

A

Gluconeogenesis and glycogenolysis

115
Q

Name the organ: After the third day of fasting, ketone bodies formed in the _____ supply the _____ and the ______ with energy.

A

Liver; brain; heart

116
Q

What role does adipose tissue play in maintaining blood glucose levels in the first three days of fasting/starvation?

A

Release of free fatty acids that can be metabolized into contributions for hepatic gluconeogensis

117
Q

Which tissues contribute the compounds required for hepatic gluconeogensis in order to maintain the blood glucose level during the first three days of fasting?

A

Peripheral tissue (lactate and alanine) and adipose tissue (free fatty acids)

118
Q

True or False? More muscle protein is degraded during days 1-3 of starvation than after several weeks of starvation.

A

True; ketone bodies become the main source of energy for the brain after several weeks of starvation and so less muscle protein is degraded compared to the first three days

119
Q

After several weeks of starvation, survival time is determined by the amount of _____ (muscle/fat) stores.

A

Fat

120
Q

Once fat stores are depleted after several weeks of starvation, _____ (protein/glucose/free fatty acid) degradation accelerates, leading to organ failure and death.

A

Protein

121
Q

What are the sources of adenosine triphosphate for muscles during brief exercise?

A

Stored adenosine triphosphate, creatine phosphate, and anaerobic glycolysis

122
Q

In addition to the sources that can be used in seconds, from which sources do muscles derive adenosine triphosphate during exercise that lasts at least several minutes?

A

Stored adenosine triphosphate, creatine phosphate, anaerobic glycolysis, and oxidative phosphorylation

123
Q

Which sources of adenosine triphosphate does the body use during exercise that lasts for hours?

A

Glycogen and free fatty acid oxidation

124
Q

What are the purposes of the metabolic changes the body undergoes during starvation?

A

To supply glucose to the brain and preserve protein structures

125
Q

What is the enzyme that esterifies plasma cholesterol?

A

Lecithin-cholesterol acetyltransferase

126
Q

What category of drugs inhibits HMG coenzyme A reductase?

A

Statins

127
Q

What enzyme catalyzes the rate-limiting reaction in cholesterol synthesis?

A

HMG-CoA reductase

128
Q

What are the two essential fatty acids?

A

Linolenic acid and linoleic acid

129
Q

What acid becomes essential in the absence of linoleic acid?

A

Arachidonic acid

130
Q

The formation of eicosanoids is dependent on the consumption of which fatty acids?

A

Essential fatty acids: linolenic and linoleic acid

131
Q

Which enzyme is responsible for the degradation of dietary triglycerides?

A

Pancreatic lipase

132
Q

Which enzyme is responsible for the degradation of triglycerides that are circulating as chylomicrons?

A

Lipoprotein lipase

133
Q

Which organs take up low-density lipoproteins from the circulation?

A

The liver and peripheral tissues with low-density lipoprotein receptors

134
Q

Which enzyme is responsible for the degradation of triglycerides circulating as intermediate-density lipoproteins?

A

Hepatic triglyceride lipase

135
Q

What is the enzyme responsible for converting nascent high-density lipoproteins into mature high-density lipoproteins?

A

Lecithin-cholesterol acetyltransferase

136
Q

What enzyme is responsible for the degradation of triglycerides that are stored within adipocytes?

A

Hormone-sensitive lipase

137
Q

What enzyme transfers cholesterol esters from high-density lipoproteins to other lipoproteins?

A

Cholesteryl ester transfer protein

138
Q

What organ releases chylomicrons into the circulation?

A

The gastrointestinal tract

139
Q

Name three lipoproteins that receive cholesterol esters from high-density lipoprotein via cholesteryl ester transfer protein.

A

Very-low-density lipoprotein, intermediate-density lipoprotein, low-density lipoprotein

140
Q

What enzyme converts chylomicrons into chylomicron remnants?

A

Lipoprotein lipase

141
Q

What organ takes up chylomicron remnants from the circulation?

A

The liver

142
Q

What organ releases very-low-density lipoprotein into the circulation?

A

The liver

143
Q

What enzymes convert intermediate-density lipoproteins into low-density lipoproteins?

A

Hepatic triglyceride lipase and lipoprotein lipase

144
Q

What enzyme converts very-low-density lipoproteins into intermediate-density lipoproteins?

A

Lipoprotein lipase

145
Q

Which apolipoprotein activates lecithin-cholesterol acyltransferase?

A

Apolipoprotein A-I Activates LCAT

146
Q

Which apolipoprotein binds to the low-density lipoprotein receptor on the liver?

A

Apolipoprotein B-100 Binds the LDL receptor

147
Q

What apolipoprotein mediates very-low-density lipoprotein secretion?

A

Apolipoprotein B-100

148
Q

Which apolipoprotein acts as a cofactor for lipoprotein lipase?

A

Apolipoprotein C-II is a Cofactor for LPL

149
Q

Which apolipoprotein mediates remnant uptake?

A

Apolipoprotein E mediates Extra (remnant) uptake

150
Q

What molecules do lipoproteins contain?

A

Cholesterol, triglycerides, and phospholipids

151
Q

Which lipoprotein delivers dietary triglycerides to peripheral tissues?

A

Chylomicrons

152
Q

Which lipoprotein is secreted only by intestinal epithelial cells?

A

Chylomicrons

153
Q

Which apolipoprotein mediates the secretion of chylomicrons from the gastrointestinal tract?

A

Apolipoprotein B-48

154
Q

Which lipoprotein delivers hepatic triglycerides to peripheral tissues?

A

Very-low-density lipoprotein

155
Q

Which organ secretes very-low-density lipoprotein into the bloodstream?

A

The liver

156
Q

Name the two major lipoprotein carriers of cholesterol

A

Low-density lipoprotein and high-density lipoprotein

157
Q

What lipoprotein carries cholesterol from the liver to the tissues?

A

Low-density lipoprotein (remember: LDL is Lousy)

158
Q

What lipoprotein carries cholesterol from the tissues to the liver?

A

High-density lipoprotein (remember: HDL is Healthy)

159
Q

Which apolipoprotein on low-density lipoprotein mediates uptake into the liver?

A

Apolipoprotein B-100

160
Q

Which lipoprotein delivers dietary cholesterol to the liver?

A

Chylomicrons (as chylomicron remnants)

161
Q

Which lipoprotein mediates the transport of cholesterol from the periphery to the liver (reverse transport)?

A

High-density lipoprotein

162
Q

Name four apolipoproteins found on chylomicrons.

A

B-48, A-IV, C-II, and E

163
Q

Which lipoprotein acts as a reservoir of apolipoprotein C and apolipoprotein E?

A

High-density lipoprotein

164
Q

Which lipoprotein is formed by the degradation of very-low-density lipoprotein in the periphery by lipoprotein lipase (via IDL as an intermediate)?

A

Low-density lipoprotein

165
Q

What three apolipoproteins are found on very-low-density lipoprotein?

A

Apolipoprotein B-100, apolipoprotein C-II, and apolipoprotein-E

166
Q

Which lipoprotein is formed by the degradation of very-low-density lipoprotein?

A

Intermediate-density lipoprotein

167
Q

What lipoprotein is secreted by both intestinal epithelial cells and the liver?

A

High-density lipoprotein

168
Q

Which lipoprotein delivers triglycerides and cholesterol to the liver for degradation into low-density lipoprotein?

A

Intermediate-density lipoprotein

169
Q

What are the two apolipoproteins found on intermediate-density lipoprotein?

A

B-100 and E

170
Q

What is another name for type I dyslipidemia?

A

Hyperchylomicronemia

171
Q

An altered apolipoprotein C-II that does not function properly produces which type of familial dyslipidemia?

A

Type I (hyperchylomicronemia); C-II is a cofactor for lipoprotein lipase and if altered, the body is unable to metabolize chylomicrons