Biochem - Metabolism (Part 3) Flashcards
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
α-1,6-glycosidic
8
Q
What type of bond is found at side-by-side linkages of glucose in glycogen?
A
α-1,6-glycosidic
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
α-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
How can you differentiate between a patient with Cori's disease and one with von Gierke's disease using blood samples?
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
What is another name for glycogen storage disease type II?
Pompe's disease
27
In a patient with McArdle's disease, would you expect increased or decreased levels of glycogen on muscle biopsy?
Increased levels of glycogen, because the muscle cannot break it down
28
What is another name for -1,4-glucosidase?
Acid maltase
29
What disease is the result of a deficiency of lysosomal -1,4-glucosidase?
Pompe;s disease (glycogen storage disease type II)
30
Pompe;s disease (glycogen storage disease type II) is associated with the enlargement of what organ?
The heart (remember: **P**ompe's trashes the **P**ump)
31
Name three organs affected in Pompe's disease.
Heart, liver, muscle
32
What is another name for glycogen storage disease type III?
Cori's disease
33
What is another name for -1,6-glucosidase?
Debranching enzyme
34
What disease is the result of a deficiency of -1,6-glucosidase?
Cori's disease (glycogen storage disease type III)
35
What is another name for glycogen storage disease type V?
McArdle's disease
36
What disease is the result of a deficiency of skeletal muscle glycogen phosphorylase?
McArdle's disease (glycogen storage disease type V)
37
A patient has painful cramping and myoglobinuria associated with strenuous exercise. What is the likely underlying metabolic deficiency?
McArdle's disease (glycogen storage disease type V) (remember: McArdle's = Muscle)
38
What bodily fluid can be used to diagnose McArdle's in a patient with severe muscle cramping after exercise?
A urinalysis will show myoglobinuria
39
What enzyme deficiency is seen in Fabry's disease?
-Galactosidase A
40
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?
Foam cells; seen in Niemann-Pick disease
41
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?
Globoid cells; seen in Krabbe's disease
42
A deficiency of the enzyme -galactosidase A leads to what disease?
Fabry's disease
43
What substrate is accumulated in Fabry's disease?
Ceramide trihexoside
44
What type of inheritance does Fabry's disease demonstrate?
X-linked recessive
45
What is the appearance of the cells that may serve as histologic confirmation of Gaucher's disease?
Gaucher's cells are macrophages that look like crumpled tissue paper
46
Name two mucopolysaccharidoses.
Hunter's syndrome and Hurler's syndrome
47
A patient shows milder symptoms and appearance similar to Hurler's syndrome but no corneal clouding; what kind of behavior patterns do you expect?
Aggressive behavior; this describes Hunter's syndrome, an X-linked mucopolysaccharidosis
48
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?
Fabry's disease
49
What substrate accumulates in a patient with a deficiency of -glucocerebrosidase?
Glucocerebroside; it accumulates in liver, spleen, and bone in Gaucher's disease
50
Name six types of sphingolipidosis.
Fabry's disease, Gaucher's disease, Niemann-Pick disease, Tay-Sachs disease, Krabbe's disease, metachromatic leukodystrophy
51
What substrate is accumulated in Niemann-Pick disease?
Sphingomyelin (remember: **No man picks [Niemann-Pick]** his nose with his **sphinger [sphingomyelinase]**)
52
What enzyme deficiency leads to Gaucher's disease?
-Glucocerebrosidase
53
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?
Tay-Sachs disease
54
What is the most common lysosomal storage disorder?
Gaucher's disease
55
A patient has developmental delay, gargoylism, airway narrowing, and corneal clouding. These characteristics are typical of which lysosomal storage disease?
Hurler's syndrome
56
Which three lysosomal storage disorders are Ashkenazi Jews at increased risk for?
Tay-Sachs, Niemann-Pick, and some forms of Gaucher's disease
57
What type of inheritance does Gaucher's disease demonstrate?
Autosomal recessive
58
A patient has hepatosplenomegaly, aseptic necrosis of the femur, and abnormal macrophages on histologic examination. These characteristics are typical of which lysosomal storage disease?
Gaucher's disease
59
What is the term for macrophages that look like crumpled tissue paper under the microscope and are associated with a lysosomal storage disease?
Gaucher's cells
60
What enzyme deficiency leads to Niemann-Pick disease?
Sphingomyelinase
61
A deficiency of the enzyme sphingomyelinase leads to what disease?
Niemann-Pick disease
62
What type of inheritance does Niemann-Pick disease demonstrate?
Autosomal recessive
63
A child has progressive neurodegeneration, hepatosplenomegaly, and a cherry-red spot on his macula. These characteristics are typical of which lysosomal storage disease?
Niemann-Pick disease
64
What enzyme deficiency leads to Tay-Sachs disease?
Hexosaminidase A (remember: Tay-Sa**X** lacks he**X**osaminidase)
65
What substrate is accumulated in Tay-Sachs disease?
GM2 ganglioside
66
What type of inheritance does Tay-Sachs disease demonstrate?
Autosomal recessive
67
Name two lysosomal storage diseases that may present with a cherry-red spot on the macula.
Niemann-Pick disease and Tay-Sachs disease
68
What enzyme deficiency leads to Krabbe's disease?
Galactocerebrosidase
69
What substrate is accumulated in Krabbe's disease?
Galactocerebroside
70
What type of inheritance does Krabbe's disease demonstrate?
Autosomal recessive
71
A patient has peripheral neuropathy, developmental delay, and optic atrophy. These characteristics are typical of which lysosomal storage disease?
Krabbe's disease
72
What enzyme deficiency leads to metachromatic leukodystrophy?
Arylsulfatase A
73
What substrate is accumulated in metachromatic leukodystrophy?
Cerebroside sulfate
74
What type of inheritance does metachromatic leukodystrophy demonstrate?
Autosomal recessive
75
A patient has central and peripheral demyelination with ataxia and dementia. These characteristics are typical of which lysosomal storage disease?
Metachromatic leukodystrophy
76
What enzyme deficiency leads to Hurler's syndrome?
-L-iduronidase
77
What substrates accumulates in Hurler's syndrome?
Heparan sulfate and dermatan sulfate
78
What pattern of inheritance does Hurler's syndrome demonstrate?
Autosomal recessive
79
What enzyme deficiency leads to Hunter's syndrome?
Iduronate sulfatase
80
What substrates are accumulated in Hunter's syndrome?
Heparan sulfate and dermatan sulfate
81
What pattern of inheritance does Hunter's syndrome demonstrate?
X-linked recessive
82
A patient has mild developmental delay, gargoylism, and airway obstruction but no corneal clouding. These characteristics are typical of which lysosomal storage disease?
Hunter's syndrome
83
Name the two lysosomal storage diseases that lead to an accumulation of heparan sulfate and dermatan sulfate.
Hunter's syndrome and Hurler's syndrome
84
Name the two lysosomal storage diseases that show x-linked recessive inheritance.
Fabry's disease and Hunter's syndrome
85
What is the name of the shuttle that moves acetyl coenzyme A from the mitochondria to the cytoplasm to participate in fatty acid synthesis?
Citrate shuttle (remember: **SY**trate = **SY**nthesis)
86
The addition of carbon dioxide to acetyl coenzyme A during fatty acid synthesis yields what molecule?
Malonyl coenzyme A
87
In acyl-CoA dehydrogenase deficiency, dicarboxylic acid levels _____ (increase/decrease) and glucose and ketone levels _____ (increase/decrease).
Increase; decrease
88
A deficiency of which enzyme in fatty acid metabolism causes an increase in dicarboxylic acids and a decrease in glucose and ketones?
Acyl-CoA dehydrogenase deficiency
89
What cofactor is required for the conversion of acetyl-CoA to malonyl-CoA during fatty acid synthesis?
Biotin; it donates the CO2 group
90
Where does fatty acid degradation occur? Where are the products of degradation consumed?
Both occur in the mitochondrion
91
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?
Carnitine shuttle (remember: **CAR**nitine = **CAR**nage of fatty acids)
92
After breakdown of fatty acids, the resulting acetyl-CoA groups can be put to which uses?
Ketogenesis or citric acid cycle
93
In which direction does the citrate shuttle move acetyl-CoA across the mitochondrial membrane?
From the mitochondria to the cytoplasm
94
In which direction does the carnitine shuttle move fatty acids across the mitochondrial membrane?
From the cytoplasm to the mitochondria
95
A deficiency of what substance will result in hypoketotic hypoglycemia?
Carnitine
96
What are the clinical sequelae of carnitine deficiency?
Weakness, hypotonia, and hypoketotic hypoglycemia due to toxic accumulation of long-chain fatty acids
97
Name two ketone bodies derived from acetyl-CoA. (These are found in individuals who have experienced prolonged starvation and diabetic ketoacidosis.)
Acetoacetate and -hydroxybutyrate
98
In a patient with high levels of circulating ketone bodies, what does the breath smell like?
Acetone (a fruity odor)
99
Which two precursors can be made into ketone bodies?
Amino acids and fatty acids
100
What is the precursor molecule to acetoacetate?
HMG coenzyme A
101
In alcoholism, the citric acid cycle is stalled due to excess NADH, causing a shunting of glucose and free fatty acids toward formation of _______ \_\_\_\_\_\_\_.
Ketone bodies
102
Which two organs can use ketone bodies as fuel during starvation?
Muscle and brain
103
Which ketone body cannot be detected by a urine test?
-Hydroxybutyrate
104
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?
Ketone bodies
105
Where in the body are ketones synthesized?
Liver
106
In which two pathological states will the body produce large amounts of ketones?
Starvation and ketoacidosis
107
The brain can convert one ketone body into two of what type of molecule?
Acetyl-CoA for use in the tricarboxylic acid cycle to generate adenosine triphosphate
108
1 gram protein or carbohydrate = ____ kcal
4
109
1 gram fat = ___ kcal
9
110
During the first three days of fasting, which four processes maintain the blood glucose level?
Hepatic glycogenolysis, adipocyte free fatty acid release, muscle and liver free fatty acid use (instead of glucose), and hepatic gluconeogenesis
111
What molecules do skeletal muscles contribute for hepatic gluconeogenesis in order to maintain the blood glucose level?
Lactate and alanine
112
What are the only triacylglycerol molecules that can contribute to gluconeogenesis?
Glycerol, propionyl-CoA (from odd-chain free fatty acids)
113
Which compounds do adipose tissues contribute for hepatic gluconeogenesis in order to maintain the blood glucose level during the first three days of starvation?
Glycerol and propionyl-CoA (from free fatty acid metabolism)
114
What two metabolic processes does the liver undergo to maintain blood glucose level in the first three days of fasting/starvation?
Gluconeogenesis and glycogenolysis
115
Name the organ: After the third day of fasting, ketone bodies formed in the _____ supply the _____ and the ______ with energy.
Liver; brain; heart
116
What role does adipose tissue play in maintaining blood glucose levels in the first three days of fasting/starvation?
Release of free fatty acids that can be metabolized into contributions for hepatic gluconeogensis
117
Which tissues contribute the compounds required for hepatic gluconeogensis in order to maintain the blood glucose level during the first three days of fasting?
Peripheral tissue (lactate and alanine) and adipose tissue (free fatty acids)
118
True or False? More muscle protein is degraded during days 1-3 of starvation than after several weeks of starvation.
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
After several weeks of starvation, survival time is determined by the amount of _____ (muscle/fat) stores.
Fat
120
Once fat stores are depleted after several weeks of starvation, _____ (protein/glucose/free fatty acid) degradation accelerates, leading to organ failure and death.
Protein
121
What are the sources of adenosine triphosphate for muscles during brief exercise?
Stored adenosine triphosphate, creatine phosphate, and anaerobic glycolysis
122
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?
Stored adenosine triphosphate, creatine phosphate, anaerobic glycolysis, and oxidative phosphorylation
123
Which sources of adenosine triphosphate does the body use during exercise that lasts for hours?
Glycogen and free fatty acid oxidation
124
What are the purposes of the metabolic changes the body undergoes during starvation?
To supply glucose to the brain and preserve protein structures
125
What is the enzyme that esterifies plasma cholesterol?
Lecithin-cholesterol acetyltransferase
126
What category of drugs inhibits HMG coenzyme A reductase?
Statins
127
What enzyme catalyzes the rate-limiting reaction in cholesterol synthesis?
HMG-CoA reductase
128
What are the two essential fatty acids?
Linolenic acid and linoleic acid
129
What acid becomes essential in the absence of linoleic acid?
Arachidonic acid
130
The formation of eicosanoids is dependent on the consumption of which fatty acids?
Essential fatty acids: linolenic and linoleic acid
131
Which enzyme is responsible for the degradation of dietary triglycerides?
Pancreatic lipase
132
Which enzyme is responsible for the degradation of triglycerides that are circulating as chylomicrons?
Lipoprotein lipase
133
Which organs take up low-density lipoproteins from the circulation?
The liver and peripheral tissues with low-density lipoprotein receptors
134
Which enzyme is responsible for the degradation of triglycerides circulating as intermediate-density lipoproteins?
Hepatic triglyceride lipase
135
What is the enzyme responsible for converting nascent high-density lipoproteins into mature high-density lipoproteins?
Lecithin-cholesterol acetyltransferase
136
What enzyme is responsible for the degradation of triglycerides that are stored within adipocytes?
Hormone-sensitive lipase
137
What enzyme transfers cholesterol esters from high-density lipoproteins to other lipoproteins?
Cholesteryl ester transfer protein
138
What organ releases chylomicrons into the circulation?
The gastrointestinal tract
139
Name three lipoproteins that receive cholesterol esters from high-density lipoprotein via cholesteryl ester transfer protein.
Very-low-density lipoprotein, intermediate-density lipoprotein, low-density lipoprotein
140
What enzyme converts chylomicrons into chylomicron remnants?
Lipoprotein lipase
141
What organ takes up chylomicron remnants from the circulation?
The liver
142
What organ releases very-low-density lipoprotein into the circulation?
The liver
143
What enzymes convert intermediate-density lipoproteins into low-density lipoproteins?
Hepatic triglyceride lipase and lipoprotein lipase
144
What enzyme converts very-low-density lipoproteins into intermediate-density lipoproteins?
Lipoprotein lipase
145
Which apolipoprotein activates lecithin-cholesterol acyltransferase?
Apolipoprotein **A**-I **A**ctivates LCAT
146
Which apolipoprotein binds to the low-density lipoprotein receptor on the liver?
Apolipoprotein **B**-100 **B**inds the LDL receptor
147
What apolipoprotein mediates very-low-density lipoprotein secretion?
Apolipoprotein B-100
148
Which apolipoprotein acts as a cofactor for lipoprotein lipase?
Apolipoprotein **C**-II is a **C**ofactor for LPL
149
Which apolipoprotein mediates remnant uptake?
Apolipoprotein **E** mediates **E**xtra (remnant) uptake
150
What molecules do lipoproteins contain?
Cholesterol, triglycerides, and phospholipids
151
Which lipoprotein delivers dietary triglycerides to peripheral tissues?
Chylomicrons
152
Which lipoprotein is secreted only by intestinal epithelial cells?
Chylomicrons
153
Which apolipoprotein mediates the secretion of chylomicrons from the gastrointestinal tract?
Apolipoprotein B-48
154
Which lipoprotein delivers hepatic triglycerides to peripheral tissues?
Very-low-density lipoprotein
155
Which organ secretes very-low-density lipoprotein into the bloodstream?
The liver
156
Name the two major lipoprotein carriers of cholesterol
Low-density lipoprotein and high-density lipoprotein
157
What lipoprotein carries cholesterol from the liver to the tissues?
Low-density lipoprotein (remember: **L**DL is **L**ousy)
158
What lipoprotein carries cholesterol from the tissues to the liver?
High-density lipoprotein (remember: **H**DL is **H**ealthy)
159
Which apolipoprotein on low-density lipoprotein mediates uptake into the liver?
Apolipoprotein B-100
160
Which lipoprotein delivers dietary cholesterol to the liver?
Chylomicrons (as chylomicron remnants)
161
Which lipoprotein mediates the transport of cholesterol from the periphery to the liver (reverse transport)?
High-density lipoprotein
162
Name four apolipoproteins found on chylomicrons.
B-48, A-IV, C-II, and E
163
Which lipoprotein acts as a reservoir of apolipoprotein C and apolipoprotein E?
High-density lipoprotein
164
Which lipoprotein is formed by the degradation of very-low-density lipoprotein in the periphery by lipoprotein lipase (via IDL as an intermediate)?
Low-density lipoprotein
165
What three apolipoproteins are found on very-low-density lipoprotein?
Apolipoprotein B-100, apolipoprotein C-II, and apolipoprotein-E
166
Which lipoprotein is formed by the degradation of very-low-density lipoprotein?
Intermediate-density lipoprotein
167
What lipoprotein is secreted by both intestinal epithelial cells and the liver?
High-density lipoprotein
168
Which lipoprotein delivers triglycerides and cholesterol to the liver for degradation into low-density lipoprotein?
Intermediate-density lipoprotein
169
What are the two apolipoproteins found on intermediate-density lipoprotein?
B-100 and E
170
What is another name for type I dyslipidemia?
Hyperchylomicronemia
171
An altered apolipoprotein C-II that does not function properly produces which type of familial dyslipidemia?
Type I (hyperchylomicronemia); C-II is a cofactor for lipoprotein lipase and if altered, the body is unable to metabolize chylomicrons
