Metabolism Flashcards
(177 cards)
1
Q
Enzyme that converts galactose to galactose-1-phosphate
A
Galactokinase (GALK)
2
Q
Upon GALK deficiency, which enzyme converts galactose to galactitol
A
Aldose reductase
3
Q
Most important clinical manifestation (might be the only one) in GALK deficiency
A
Cataracts
4
Q
Substrate with high osmotic activity that accumulates in the lens leading to cataract formation in patients with GALK deficiency
A
Galactitol
5
Q
Intermediate substrate that is accumulated in the more serious form of galactosemia due to deficiency of galactose-1-phosphate uridyl transferase (GALT)
A
Galactose-1-phosphate
6
Q
What are the clinical manifestations of GALT deficiency in the newborn period
A
Vomiting, lethargy, and failure to thrive
7
Q
Deficient enzyme in Fabry disease
A
alpha-Galactosidase A
8
Q
Accumulated substrate in Fabry disease
A
Ceramide trihexoside
9
Q
Mode of inheritance of Fabry disease
A
X-linked recessive
10
Q
Clinical manifestations of Fabry disease
A
- Neuropathy (mainly burning sensation)
- Angiokeratomas
- Hypohidrosis
- Can also develop cataracts!*
11
Q
Disease that results from deficiency of glucose-6-phosphatase
A
Von Gierke disease
12
Q
Clinical manifestations of von Gierke disease
A
- Hypoglycemia
- Lactic acidosis
- Hepatomegaly
- Hipertriglyceridemia
13
Q
Deficient enzyme in Tay-Sachs disease
A
Hexosaminidase A
14
Q
Accumulated substrate in Tay-Sachs disease
A
GM2 ganglioside
15
Q
Clinical manifestations of Tay-Sachs disease
A
- Cherry-red spot on macula*
- Neurodegeneration
- Macrocephayl
- Abnormal startle reflex with acoustic stimuli
16
Q
Deficient enzyme in Niemann-Pick disease
A
Sphingomyelinase
17
Q
Accumulated substrate in Niemann-Pick disease
A
Sphingomyelin
18
Q
Clinical manifestations of Niemann-Pick disease
A
- Neurodegeneration
- Cherry red spot on macula*
- Hepatosplenomegaly* (this is the differentiating symptom with Tay-Sachs disease)
19
Q
Characteristic type of cells seen in the reticuloendotelial and nervous systems in Niemann-Pick disease
A
Lipid-laden cells (foam cells)
20
Q
Branched-chain aminoacids
A
Leucine, Isoleucine, and Valine
21
Q
Deficient enzyme in maple syrup disease
A
Branched-chain ketoacid dehydrogenase
22
Q
Enzyme deficiency in homocystinuria
A
Cystathionine-B-synthase
23
Q
Tetrahydrobiopterin works as a cofactor in which reactions
A
- Synthesis of serotonin
- Synthesis of tyrosine
- Synthesis of DOPA
24
Q
Clinical manifestations of Gaucher disease
A
- Hepatosplenomegaly
- Osteoporosis - avascular necrosis of the femur*
- Pancytopenia/thrombocytopenia
25
Characteristic cell observed in Gaucher disease
Lipid-laden macrophage resembling crumpled tissue paper (Gaucher cell)
26
Deficient enzyme in Gaucher disease
Glucocerebrosidase
27
Accumulated substrate in Gaucher disease
Glucocerebroside
28
Deficient enzyme in metachromatic leukodystrophy
Arylsulfatase A
29
Clinical manifestations of metachromatic leukodystrophy
- Motor symptoms (ataxia) and dementia
| - Polyneuropathy
30
Accumulated substrate in metachromatic leukodystrophy
Cerebroside sulfate
31
Under anaerobic conditions, which enzyme regenerates NAD+ in order to keep glyceraldehyde-3-phosphate dehydrogenase working (and therefore, glycolysis)
Lactate dehydrogenase
32
Number of ATP produces in aerobic glycolysis per glucose molecule
32 net ATPs through the malate-shuttle (heart and liver) and 30 net ATPs through the G3P shuttle (muscle)
33
Main source of NADPH
HMP shunt (pentose phosphate pathway)
34
Rate limiting enzyme in the oxidative phase of the pentose phosphate shunt
Glucose-6-P dehydrogenase
35
Necessary molecule to keep glutathione reduced
NADPH (coming from the pentose phosphate pathway)
36
Histological difference between PK deficiency and G6PD
There are no Heinz bodies in PK defiency
37
In abscence of fructokinase, what enzyme is in charge of phosphorylating fructose to fructose-6-P
Hexokinase
*Normally, fructokinase phosphorylates fructose to fructose-1-P
38
Enzyme deficient in essential fructosuria
Fructokinase
39
Enzyme deficient in fructose intolerance
Aldolase B
40
Clinical manifestations of fructose intolerance
* Lethargy, vomiting
* Liver damage, hyperbilirubinemia, jaundice
* Hypoglycemia
* Hyperuricemia
* Renal proximal tubule defect (Fanconi)
41
Metabolic pathways that are inhibited in fructose intolerance due to low phosphate
Glycogenolysis and gluconeogenesis
42
Diagnosis of fructose intolerance
Symptoms + reducing sugars in urine
*Urine dipstick will be negative because it only Works for glucose
43
Aldolase B metabolizes fructose-1-P to what 2 intermediates
Dihydroxyacetone-P (DHAP) and glyceraldehyde
*Both can be transformed into G3P and be used in glycolysis, glycogenesis, gluconeogenesis
44
Pyruvate dehydrogenase cofactor that is inhibited by arsenic
Lipoic acid
45
Pyruvate dehydrogenase cofactors
1. Thiamine
2. Lipoic acid
3. CoA
4. FAD
5. NAD+
*Tender Loving Care For Nancy
46
Accumulated substrates in pyruvate dehydrogenase deficiency
Pyruvate gets shunted to lactate (via LDH) and alanine (via ALT)
47
Mode of inheritance of pyruvate dehydrogenase deficiency
X-linked
48
Clinical manifestations of pyruvate dehydrogenase deficiency
* Neurologic defects (microcephaly and mental retardation)
* Lactic acidosis
* Increased serum alanine starting in infancy
49
Treatment for pyruvate dehydrogenase deficiency
*Increase intake of ketogenic nutrients (high fat, high lysine and leucine)
50
Reaction catalyzed by pyruvate dehydrogenase
Pyruvate + NAD + CoA = acetyl-CoA + CO2 + NADH
*Links glycolysis to TCA cycle
51
Enzyme deficient in Von Gierke's disease
Glucose-6-phosphatase
52
Signs and symptoms of Von Gierke's disease
* Severe fasting hypoglycemia
* Hepatomegaly (accumulation of glycogen in the liver)
* Lactic acidosis
* Hyperlipidemia
* Hyperuricemia
* Characteristic DOLL-LIKE FACIES (with short stature, protruding abdomen, and emaciated extremities)
53
Treatment for Von Gierke's disease
Frequent oral glucose/cornstarch and avoidance of fructose and galactose
54
Deficient enzyme in Pompe's disease
Acid maltase (lysosomal acid a-1,4-glucosidase with a-1,6-glucosidase activity)
55
Signs and symptoms of Pompe's disease
* Cardiomegaly and cardiac failure
* Hepatomegaly
* Exercise intolerance
PomPe trashes the PumP (1,4) - heart, liver, and muscle
56
Histologic finding in Pompe's disease
Glycogen-like material in inclusion bodies
57
Deficient enzyme in Cori's disease
Glycogen debranching enzyme (a-1,6-glucosidase)
58
Signs and symptoms of Cori's disease
* Accumulation of excessive amounts of glycogen with altered structure (DEXTRIN-LIKE in cytosol)
* Hyperglycemia
* Hyperlipidemia
* Failure to thrive
* Myopathy and cardiomyopathy
Abscence of hepatomegaly can be used to distinguish between this disease and Von Gierke's
59
Deficient enzyme in Andersen's disease
Branching enzyme
60
Signs and symptoms of Andersen's disease
* Muscle weakness (infantile hypotonia)
* Exercise intolerance
* Dilated cardiomyopathy and heart failure
* Progressive liver failure and cirrhosis
61
Treatment for Andersen's disease
Liver transplantation
62
Deficient enzyme in McArdle's disease
Muscle glycogen phosphorylase (myophosphorylase)
63
Signs and symptoms of McArdle's disease
* Painful muscle cramps
* Myoglobinuria with strenous excercise
* Exercise intolerance
These patients have a SECOND WIND PHENOMENON during exercise due to increased muscular blood flow
64
Deficient enzyme in Hers disease
Hepatic glycogen phosphorylase
65
Signs and symptoms of Hers disease
* Mild hypoglycemia
* Hyperlipidemia
* Hyperketosis
* Hepatomegaly
* Growth retardation in early childhood
66
Autosomal recessive glycogen storage diseases
"Very Poor Carbohydrate Metabolism"
Types 1 (Von Gierke), 2 (Pompe), 3 (Cori), 5 (McArdle)
67
Gluconeogenesis irreversible enzymes
"Pathway Produces Fresh Glucose"
* Pyruvate carboxylase
* PEP carboxykinase
* Fructose-1,6-bisphosphatase
* Glucose-6-phosphatase
68
Gluconeogenesis enzyme that transforms pyruvate into oxaloacetate (Malate shuttle through mitochondria)
Pyruvate carboxylase
*Activated by Acetyl-CoA, requires biotin and ATP
69
Gluconeogenesis enzyme that transforms oxaloacetate into PEP
PEP carboxykinase
*Requires GTP
70
Allosteric regulators of fructose-1,6-biphosphatase
(+) Citrate
(-) AMP, fructose-2,6-bisphosphate (because if this molecule increases, PFK-1 activity is initiated, and therefore the opposite reaction takes place for glycolysis)
71
Cell organelle in which G6P is contained
Endoplasmic reticulum
72
Name the 3 substrates for gluconeogenesis
* G3P (from adiposte tissue)
* Lactate (from anaerobic glycolysis)
* Gluconeogenic aminoacids (from muscle protein)
73
Name the 2 major functions of the HMP shunt
* Provide NADPH
| * Provide Ribose-5-P
74
Enzyme that catalyzes the oxidative (irreversible) reaction in the HMP shunt
Glucose-6-dehydrogenase
*Glucose-6-P to ribulose-5-P, 1 CO2 and 2 NADPH
75
HMP shunt phase that results in the formation of ribose-5-P
Nonoxidative phase (reversible)
76
Mode of inheritance of G6PD deficiency
X-linked recessive
77
Why are there Heinz bodies in G6PD deficiency
Because hemoglobin denatures and precipitates, due to the presence of reactive oxygen species
78
Signs and symptoms of G6PD deficiency
Episodic hemolysis characterized by anemia, hemoglobinuria, jaundice
79
Characteristic cells observed in G6PD deficiency
Bite cells
*Result from phagocytic removal of Heinz bodies by splenic macrophages - "Bite into some Heinz ketchup"
80
Hemolysis is precipitated in G6PD deficiency by...
Oxidizing agents
* Fava beans
* Primaquine
* Anti-TB drugs
* Dapsone
* Infections (most common cause)
81
G6PD deficiency provides increased resistance to what type of infection
Malaria
82
G6PD deficiency increases susceptibility to what type of infections
Catalase + infections
*Differentiate from CGD with NBT test (will be negative in the case of G6PD deficiency)
83
End product of alcohol metabolism
Acetate
84
Enzyme that converts alcohol into acetaldehyide
Alcohol dehydrogenase
85
Drug that inhibits alcohol dehydrogenase
Fomepizole
86
Clinical uses of Fomepizole
Overdoses of methanol and ethylene glycol
87
Enzyme that converts acetaldehyde into acetate
Acetaldehyde dehydrogenase
88
Drug that inhibits acetaldehyde dehydrogenase
Disulfiram
89
Clinical uses of Disulfiram
Discourage drinking
90
Metabolic reactions that are favored in alcoholism due to increased NADH/NAD+ ratio
1. Pyruvate to lactate (lactic acidosis)
2. Oxaloacetate to malate (prevents gluconeogénesis and causes fasting hypoglycemia)
3. DHAP to G3P (combines with FA to make triglycerides, leading to hepatosteatosis)
91
Reversible enzyme that catalyzes the formation of lactate from pyruvate
Lactate dehydrogenase
92
Deficient proteins in abetalipoproteinemia (and hypo-)
ApoB48 and B100
93
Consequences of absent apoB48 and B100
* Chylomicrons cannot be released into lymphatics
* VLDL cannot be released from hepatocytes intro the bloodstream
* Low serum TG and Ch
* Accumulation of fat in enterocytes and hepatocytes
* Malabsorption of vitamins A and E
94
Signs and symptoms of hypolipidemias
* Steatorrhea
* Cerebellar ataxia
* Pigmentary degeneration of the retina
* Acanthocytes
* Loss of night vision
95
Allosteric regulators of hormone sensitive lipase
(-) insulin
| (+) epinephrine and cortisol
96
Pathogenesis of medium-chain acyl-CoA dehydrogenase deficiency (MCAD)
Decreased ability to break down fatty acids into acetyl-CoA
97
Accumulated substrate in MCAD
Fatty acyl carnitines in the blood (8 to 10 carbons) AND dicarboxylic acids
98
Important serologic characteristic of MCAD
Hypoketotic hypoglycemia and hyperammonemia
*Decreased beta oxidation in fasting increases reliance on proteolysis to supply glucose and ATP - aminoacid degradation produces ammonia that is converted to urea (this requires ATP) - with low ATP levels, activity of urea cycle decreases and ammonia builds up
99
Infants or children with MCAD can be predisposed to...
Sudden death
100
MCAD treatment
* Avoid fasting
* Increase intake of carbohydrates
* IV glucose
101
Deficient enzyme in Krabbe disease
Galactocerebrosidase
102
Accumulated substrate in Krabbe disease
Galactocerebroside
103
Signs and symptoms of Krabbe disease
* Developmental delays in childhood
* Peripheral neuropathy
* Optic atrophy
* Globoid cells
104
Only X-linked recessive lisosomal storage disease
Fabry disease
105
First enzyme of the urea cycle
Carbamoyl phosphate synthetase 1
*Substrate: HCO3 (CO2) + NH3 + 2ATP
106
Main allosteric activator of Carbamoyl phosphate synthetase 1
N-acetylglutamate
*Therefore, a defect in N-acetylglutamate synthase also results in hyperammonemia
107
Reaction catalyzed by ornithine transcarbamylase
Carbamoyl phosphate + ornithine = citrulline
108
Enzyme that breaks down arginine to form urea and ornithine
Arginase
109
Metabolic pathway inhibited by hyperammonemia (and why)
An increase in NH3 leads to a depletion in alpha-ketoglutarate, inhibiting the TCA cycle
110
Signs and symptoms of hyperammonemia
* Tremor (asterixis)
* Slurring of speech
* Somnolence
* Vomiting
* Cerebral edema (and seizures)
* Blurring of vision
111
Pharmacologic management of hyperammonemia
1. Lactulose (acidify the GI tract and trap NH4 for excretion)
2. Antibiotics (i.e. Rifaximin, to decrease colonic ammoniagenic bacteria)
3. Benzoate, phenylacetate, or phenylbutyrate to react with glycine or glutamine, forming products that are renally excreted
112
Only urea cycle enzyme deficiency that is X-linked recessive
Ornithine transcarbamylase deficiency
*Most common urea cycle enzyme deficiency
113
Laboratory findings in ornithine transcarbamylase deficiency
* High NH4 and glutamine
* Low BUN
* Orotic acid in blood and urine (crystals in diaper!)
114
Accumulated substrate in ornithine transcarbamylase deficiency
Carbamoyl phosphate
*Converted to orotic acid, as part of the pyrimidine synthesis pathway
115
Mode of inheritance of carbamoyl phosphate synthetase 1 deficiency
Autosomal recessive
116
Laboratory findings in carbamoyl phosphate synthetase 1 deficiency
* High NH4 and glutamine
| * Low BUN
117
Deficient enzyme in classic PKU
Phenylalanine hydroxylase
118
Cofactor needed by phenylalanine hydroxylases that, if deficient, can lead to malignant PKU
Tetrahydrobiopterin (BH4)
119
Signs and symptoms of PKU
* Mental retardation
* Musty odor
* Microcephaly
* Seizures
* Eczema
120
PKU treatment
* Decrease phenylalanine and increase tyrosine in diet
* BH4 supplementation (if deficient)
* Avoid ASPARTAME
121
Aminoacid that becomes essential in PKU
Tyrosine
122
Laboratory findings in maple syrup disease
Increased alpha-ketoacids in the blood, especially those of leucine
*Leucine is neurotoxic
123
Signs and symptoms of maple syrup disease
* Urine has a caramel color and a sweet odor (maple syrup)
* Mental retardation
* Abnormal muscle tone
* Ketosis
* Coma and death
* Vomiting and por feeding
124
Maple syrup disease treatment
* Restriction of isoleucine, leucine, and valine
| * Thiamine supplementation
125
Characteristic laboratory finding in malignant PKU
Hyperphenylalaninenemia with increased PROLACTIN
*As tyrosine hydroxylase also needs BH4, there are low levels of dopamine too, leading to decreased inhibition of dopamine!
126
Dopamine beta-hydroxylase cofactors
Vitamin C and Cu2+
127
Rate-limiting enzyme in heme synthesis
Aminolevulinate synthase
128
Vitamin deficiencies that result in high homocysteine levels in the bloodstream
* B12 (homocysteine methyltransferase cofactor)
* B9 (used by the enzyme homocysteine methyltransferase to regenerate methionine from homocysteine)
* B6 (used by cystathionine synthase to metabolize homocysteine)
129
Functional difference between a kinase and a phosphorylase
A kinase phosphorylates using a phosphate group from a high-energy molecule (usually ATP), while a phosphorylase does not use ATP
130
Functional difference between a synthase and a synthetase
A synthase uses an energy source, while the synthetase doesn't
131
Location of hexokinase
Most tissues, except liver and pancreatic beta cells
132
Location of glucokinase
Liver and pancreatic beta cells
133
Hexokinase kinetics
* Low Km (high affinity)
* Low Vmax (reduced capacity)
* Not induced by insulin
* Inhibited by glucose-6-phosphate
134
Glucokinase kinetics
* High Km (low affinity)
* High Vmax (high capacity)
* Induced by insulin
* No negative feedback by glucose-6-phosphate, inhibited by fructose-6-phosphate
135
Number of ATPs produced in the cytoplasms during glycolysis
2
136
Rate-limiting enzyme of glycolysis
PFK-1
137
Signs and symptoms of arsenic poisoning
* Vomiting
* Rice-wáter stools
* Garlic breath
* QT prolongation
138
Electron transport chain (ETC) complex that uses NADH
Complex 1
139
Complex 1 poisons
Rotenone and high dose barbiturates
140
Electron transport chain (ETC) complex that uses FADH
Complex 2 (succinate dehydrogenase)
141
Electron transport chain (ETC) complexes that serve as proton pumps
1, 3 and 4
142
Mitochondrial location were protons accumulate to drive ATP synthesis
Intermembrane space
143
Mechanisms of action of uncoupling agents of the electron transport chain (ETC)
Increase permeability of the inner mitochondrial membrane, causing a decrease in proton gradient and increase in oxygen consumption
*Net result is ATP synthesis stop and production of HEAT (because electron transport continues)
144
Examples of uncoupling agents of the electron transport chain (ETC)
* 2,4-Dinitrophenol (illicit use for weight loss)
* Aspirin (overdose)
* Thermogenin (brown fat)
* Alcohol
145
Electron transport chain (ETC) complex inhibited by Antimycin A
Complex 3
146
Electron transport chain (ETC) complex inhibited by CO and cyanide
Complex 4
147
Electron transport chain (ETC) complex inhibited by oligomycin
Complex 5 (ATP synthase)
148
Classis galactosemia predisposes neonates to sepsis due to which bacteria
E. coli
149
Enzyme that converts sorbitol to glucose
Sorbitol dehydrogenase
150
Sites deficient in sorbitol dehydrogenase and are therefore in danger of osmotic damage in case of sorbitol accumulation
* Lens
* Retina
* Kidney
* Schwann cells
151
Dairy products that lactose intolerant patients can eat
* Unpasteurized yogurt (contains lactobacillus)
| * Cheese (contains very small amounts of lactose)
152
Name the 10 essential aminoacids
"These Ten Valuable Aminoacids Have Long Preserved Life In Men"
Threonine, Tryptophan, Valine, Arginine, Histidine, Leucine, Phenylalanine, Lysine, Isoleucine, Methionine
153
Out of the essential aminoacids, which are glucogenic
"I met his valentine, she is so sweet"
* Methionine
* Histidine
* Valine
154
Out of the essential aminoacids, which are ketogenic
* Leucine
| * Lysine
155
Acidic aminoacids (negatively charged at body pH)
* Aspartic acid
| * Glutamic acid
156
Basic aminoacids (no charge at body pH)
"His lies are basic"
* Histidine
* Lysine
* Arginine
157
Aminoacids that are required during periods of growth
Arginine and lysine
158
Most common enzyme deficiency leading to malignant PKU
Dehydrobiopterin reductase deficiency
159
Pathogenesis of cystinuria
Hereditary defect of renal PCT and intestinal aminoacid transporter that prevents reabsorption of cystine, ornithine, lysine, and arginine (COLA)
160
Cystinuria treatment
* Urinary alkalinization (eg, potassium citrate, acetazolamide)
* Chelating agents (eg, penicillamine)
161
Laboratory test used to diagnose cystinuria
Urinary cyanide-nitroprusside test
162
How long does it take until glycogen stores are depleted and gluconeogénesis is required
12-18 hours
163
Functional difference between lipoprotein lipase (LPL) and hormonse-sensitive lipase
LPL degrades TG circulating in chylomicrons and VLDLs (found on vascular endotelial surface), while hormone-sensitive lipase degrades TG stored in adipocytes
164
Molecule in charge of mediating the transfer of colesterol esters from HDL to other lipoprotein particles
Cholesterol ester transfer protein (CETP)
165
Function of apolipoprotein E
Mediates remntant uptake (everything except LDL)
*Present in almost every lipoprotein (except LDL)
166
Function of apolipoprotein A-1
Activates lecithin colesterol acyltransferase (LCAT)
*Present in HDL and chylomicrons
167
Function of apolipoprotein C-2
Lipoprotein lipase cofactor that catalyzes cleavage
*Must be present in chylomicrons and VLDL, also present in HDL
168
Function of apolipoprotein B-48
Mediates chylomicron secretion into lymphatics
169
Function of apolipoprotein B-100
Binds to LDL receptor
170
Defective gene in abetalipoproteinemia
Microsomal triglyceride transfer protein (MTP) gene
171
Substrates used by cystathionine synthase to produce cystathionine
Homocysteine and serine
172
Substrate used to synthesize cholesterol
Acetyl-CoA
173
Rate-limiting enzyme of colesterol synthesis
HMG-CoA reductase
*Located in the smooth endoplasmic reticulum (SER)
174
Activators of HMG-CoA reductase
Insulin and thyroid hormones
175
Inhibitors of HMG-CoA reductase
Statins, glucagon, and glucocorticoids
*Also negatively regulated by cholesterol
176
Metabolic intermediate of colesterol synthesis that is also used for
1. Synthesis of CoQ
2. Synthesis of dolichol PPi for N-linked glycosylation of proteins
3. Prenylation of proteins (eg, p21ras protein)
Farnesyl PPi
177
Hydrophilic vitamin that is pharmacologicaly used to inhibit hormonse-sensitive lipase
Niacin
