Metabolism Flashcards
1
Q
Reactions that take place in the mitochondria: 6
A
- Beta oxidation
- Actetyl-CoA production
- TCA cycle
- Oxidative phosporilation
- Ketogenesis
2
Q
Reactions that take place in the cell’s cytoplasm
A
- Glycolisis
- HMP shunt: ruta pentosas
- Synthesis:
- Steroids (SER)
- Proteins (RER)
- Fatty acids
- Cholesterol
- Nucleotides
3
Q
Reactions that take place both in the mitochondria and the cytoplasm
A
HUGs take two
Heme synthesis
Urea cycle
Gluconeogenesis
4
Q
Combines 2 molecules into 1 using an energy source
A
Synthase
5
Q
Combines 2 molecules into 1 without using an energy source
A
Synthetase
6
Q
Rate-determing enzyme of glycolisis
A
Phosphofructokinase-1 (PFK-1)
7
Q
Rate-determing enzyme of gluconeogenesis
A
Fructose -1,6 - biphosphatase
8
Q
Rate-determing enzyme of TCA cycle
A
Isocitrate dehydrogenase: It’s the citrate cycle
9
Q
Rate-determing enzyme of glycogenesis
A
Glycogen synthase
10
Q
Rate-determing enzyme of glycogenolysis
A
Glycogen phosphorylase
11
Q
Rate-determing enzyme of HMP shunt
A
G6PD
12
Q
Rate-determing enzyme of de novo pyrimidine synthesis
A
Carbamoyl phosphate synthetase II
13
Q
Rate-determing enzyme of urea cycle
A
Carbamoyl phosphate synthetase I
14
Q
Rate-determing enzyme of de novo purine
A
Glutamine-PRPP amidotransferase
15
Q
Rate-determing enzyme of fatty acid synthesis
A
Acetyl-CoA carboxylase
16
Q
Rate-determing enzyme of Ketogenesis
A
HMG-CoA synthase
17
Q
Rate-determing enzyme of Cholesterol synthesis
A
HMG-CoaA reductase
18
Q
Regulator of PFK-1
A
Fructose-2,6-biphosphate
19
Q
Arobic metabolism of glucose yelds
A
32 net ATP: malate-aspartate shuttle (heart and liver)
30 net ATP: glycerol-3-phosphate shuttle (muscle)
20
Q
Anaerobic metabolism of glucose yelds
A
2 ATP
21
Q
Toxic that causes glycolysis to produce zero net ATP
A
Arsenic
22
Q
TPP carries
A
Aldehydes
23
Q
Biotin carries
A
CO2
24
Q
Tetrahydrofolates carry
A
1-carbon units
25
S-adenosylmethionine carries
Ch3 groups
26
Product of the HMP shunt
NADPH
27
NAD is used in
catabolic processes
28
NADH is used in
Anabolic processes
29
At low glucose concentrations
Hexokinase sequesters glucose in the tissue
30
At high glucose concentrations
Excess glucose is stored in the liver
31
Location of glucokinase
Liver
| Beta cells of pancreas
32
Location of hexokinase
Most tissues
| Except liver and beta cells of pancreas
33
Km of hexokinase
Lower: higher affinity
34
Km of glucokinase
Higher: lower affinity
35
Vmax of hexokinase
Lower: lower capacity
36
Vmax of glucokinase
Higher: higher capacity
37
Induced by insuline: hexokinase or glucokinase?
Glucokinase
38
Feedback-inhibited by glucose-6-phosphate
Hexokinase
39
Feedback-inhibited by fructose-6-phosphate
Glucokinase
40
Reactions that require ATP for glycolisis
Glucose to glucose-6-P (hexokinase)
| Fructose-6-P to fructose-1,6-BP (PFK1)
41
Glucagon enhances FBPase-2 or PFK2?
FBPase2
42
Insulin enhances FBPase-2 or PFK2?
PFK2
43
Fructose-2,6-biphosphate acts as a positive alosteric regulator for
PFK-1: produce more fructose-1,6,BP for glycolysis
44
Mitochondrial enzyme complex linking glycolisis and TCA cycle
Pyruvate dehydrogenase complex
45
Pyruvate dehydrogenase active in fasting/fed state?
Fed
46
Pyruvate dehydrogenase complex cofactors
```
The Lovely Coenzimes For Nerds:
Tiamine
Lipoic acid
CoA
FAD
NAD
```
47
Arsenic inhibits
Lipoic acid (cofactor for pyruvate dehydrogenase complex)
48
Arsenic poisoning clinical findings
1. Vomiting
2. Rice-water stools
3. Garlic breath
4. QT prolongation
49
Pyruvate dehydrogenase complex deficiency: heredability
X-linked
50
Findings of a pyruvate dehidrogenase complex deficiency
1. Neurologic defects
2. Lactic acidosis
3. High serum alanine (starting infancy)
51
Pyruvate dehydrogenase complex deficiency: consequences
Excess pyruvate gets shunt to lactate (LDH) and alanine (ALT)
52
Tratment of Pyruvate dehydrogenase complex deficiency:
Intake of ketogenic nutrients:
- Intake of lysine and leucine
- High fat content
53
the onLy pureLy ketogenic aminoacids
Lysine
| Leucine
54
Lactic acid dehydrogenase is the end of anaerobic glycolisis. This is the major pathway in
```
RBC
WBC
Kidney Medulla
Lens
Testes
Cornea
```
55
TCA cycle yelds per glucose
```
6 NADH
2FADH2
4CO2
2GTP=
20ATP
```
56
TCA cycle substrates
Citrate is Kreb's Starting Substrate For Making Oxaloacetate:
```
Citrate
alpha ketoglutarate
Succinyl-CoA
Succinate
Fumarate
Malate
Oxaloacetate
```
57
1 NADH via ATP synthase yields
2.5 ATP
58
1 FADH2 via ATP synthase yields
1.5 ATP
59
Rotenone inhibits
Complex ONE inhibitor
60
Antimycin inhibits
Complex 3: an-3-micyn
61
Cyanide and CO inhibit
Complex 4: COCN: 4 letters
62
ATP synthesase complex V inhibitor
Oligomycin
63
Uncoupling agents of AT synthase
2,4 Dinitrophenol
Aspirin
Thermogenin (brown fat)
64
Gluconeogenesis irreversible enzymes
Pathway Produces Fresh Glucose
1. Pyruvate carboxylase
2. Phophoenolpyruvate carboxylkinase
3. Fructose-1,6-biphosphatase
4. Glucose-6-phosphatase
65
Gluconeogenesis takes place in
Liver mainly
Kidney
Intestinal epithelium
66
Fatty acids that can participate in the TCA cycle
Odd-chain fatty acids: they yeld 1 propionyl CoA
67
Process that doesn't use or produce ATP
HMP shunt
68
HMP shunt yelds
NADPH
| Ribose
69
HMP shunt takes palce in
Cytoplasm
70
Phases of HMP shunt
Oxidative: irreversible
Nonoxidative: reversible
71
Rate limiting step of HMP shunt
Glucose 6P dehydrogenase
72
Why is G6PD so important in RBC
It produces NADPH necessary to keep glutathione reduced to detoxify free radicals: its lack leads to hemolytic anemia due to poor RBC defense against oxidising agents
73
Oxidising agents important in G6PD deficiency
Fava beans: favismo
Sulfonamides
Primaquine
Antituberculosis drugs
74
Heredability in G6PD deficiency
X linked
75
G6PD deficiency is more common in
African Americans: it offers more resistance to malaria
76
Anatomopathological findings in G6PD deficiency
Bite into some Heinz ketchup
1. Heinz bodies: denatured Hb precipitates inside cell
2. Bite cells: splenic macrophages phagocyte Heinz bodies
77
Disorders of fructose metabolism
1. Essential fructosuria
| 2. Fructose intolerance
78
Disorders of galactose metabolism
1. Galactokinase deficiency
| 2. Classic galactosemia: G-uridyltransferase
79
Essential fructosuria is due to a defect in...
Fructokinase
80
Fructose intolerance is due to a defect in
Aldolase B
81
Symptoms of fructose intolerance
- Hypoglucemia: fructose 1 P accumulates causing a deficit of phosphate which results in inhibition of glycogenolysis and gluconeogenesis
- Jaundice
- Cirrhosis
- Vomiting
82
Treatment of fructose intolerance
No intake of fructose and sucrose (glucose+fructose): fruit, juice, honey
83
May present as a failure to track objects or develop a social smile
infantile cataracts: galactokinase deficiency
84
Absence of galactose-1-phosphate-uridyltransferase
Classic galactosemia
85
Toxic substance that accumulates in galactosemia
Galactitol
86
Symptoms of classic galactosemia
1. Failure to thrive
2. Jaundice
3. Hepatomegaly
4. Infantile cataracts
5. Intellectual disability
87
Urine dipstick in fructose intolerance
Negative: it tests for glucose only
88
High blood levels of galactose result in the conversion of
Galacticol via aldose reductase:
| Danger it is osmotically active
89
Glucose transforms into Sorbitol via
Aldose reductase
90
Sorbitol transforms into Fructose via
Sorbitol dehydrogenase
91
Aldose reductase is present in
```
LuRKS
Lens
Retina
Kidneys
Schwann cells
```
92
Aldose reductase
Sorbitol dehydrogenase
Both present in
Liver
Ovaries
Seminal vesicles
93
Primary lactase deficiency
Age dependent decline after childhood: asians, african and native americans
94
Secondary lactase deficiency
Loss of brush border lactase due to GE
95
Congenital lactase deficiency
Rare
| Defective gene
96
Findings in lactase deficiency study
Stool: low pH
Breath: high H content with lactose hydrogen breath test
Intestinal biopsy: normal mucosa if hereditary lactose intolerance
97
Clinical findings in lactase deficiency
Bloating
Cramps
Flatulence
Osmotic diarrea
98
Essential amino acids, glucogenic
I MET HIS VALentine, she is so SWEET
Methionine
Histidine
Valine
99
Basic Aa
His lies are so basic:
Histidine
Lysine
Arginine
100
Urea compounds
CO2
NH3
Aspartate
101
Allosteric activator of Carbamoyl phosphate synthetase I
N-acetylglutamate
102
Ammonia is transported by
Alanine in the Cahill Cycle
103
Cori cycle
Glucose-Piruvate-Lactate from liver to muscle
104
Hyperammonemia results in
Excess NH3 which deplets alpha-ketoglutarate, leading to inhibition of TCA cycle
105
Treatment of hyperammonemia
1. Limit protein in diet
2. Lactulose to acidify the GI tract and trap NH4
3. Rifaximine to low down colonic ammoniagenic bacteria
Benzoate/phenylacetate/phenylbutirate: form renally excretable products
106
Symptoms of hyperammonemia
1. Tremor: asterixis
2. Slurring of speech
3. Somnolence
4. Vomiting
5. Cerebral edema
6. Blurring of vision
107
Most common urea cycle disorder
Ornithine transcarbamylase deficiency
108
Ornithine transcarbamylase deficiency: heridability
X-linked
109
Consecuence of Ornithine transcarbamylase deficiency
1. Interferes with body's ability to eliminate ammonia
| 2. Excess carbamoyl phophate is converted to orotic acid
110
Findings of Ornithine transcarbamylase deficiency
1. High orotic acid in blood and urine
2. Low BUN
3. Symptoms of hyperammonemia
NO MEGALOBLASTIC ANEMIA vs Orotic aciduria!
111
What aa is required for heme synthesis?
GLycine
112
What aa is required for creatinine synthesis?
Arginine
113
What aa is required for Melatonin synthesis?
Serotonin
114
What aa is required for Histamine synthesis?
Histidine
115
What aa is required for urea synthesis?
Arginine
116
What aa is required for NO synthesis?
Arginine
117
Phenylketonuria is due to
Low phenylalanine hydroxilase
118
Malignant Phenylketonuria is due to
Low tetrahydrobiopterin BH4 cofactor
119
Tyrosin Aa becomes essential
Phenylketonuria
120
Tratment of Phenylketonuria
Low phenylalanine and high tyrosine in diet
| Tetrahydrobiopterin supplementation
121
Maternal Phenylketonuria
```
Lack of proper dietary therapy during pregnancy:
Children with microcephaly
intellectual disability
growth retardation
congenital heart defects
```
122
Screening for Phenylketonuria takes place
2-3 days after birth: normal at birth because of maternal enzyme during fetal life
123
Musty body odor
Phenylketonuria: disorder of AROMATIC amino acid metabolism
124
Artificial sweetener aspartame to be avoided in
Phenylketonuria, it contains phenylalanine
125
Findings of Phenylketonuria
1. Intellectual disability
2. Growth retardation
3. Seizures
4. FAIR SKIN
5. Eczema
6. MUSTY BODY ODOR
126
Maple syrup urine disease
Blocked degradation of branched amino acids: Isoleucine, Leucine, Valine: I Love Vermont maple syrup from maple trees with b1ranches
Due to low branched-chain alpha ketoacid dehydrogenase (B1)
127
Maple syrup urine disease: blood analysis
High alpha ketoacids (s/t leucine)
128
Presentation of Maple syrup urine disease
Vomiting
Poor feeding
Urine smells like maple syrup
129
Treatment Maple syrup urine disease
Restriction of isoluecine, leucine and valine in diet
| Thiamine supplementation
130
Alkaptonuria, cause
Deficiency of homogentistate oxidase
131
Error in the Degradative pathway of tyrosine to fumarate
Alkaptonuria
132
Bluish-black connective tissue in alkaptonuria is due to
Pigment forming homogentisic acid
133
Findings in alkaptonuria
1. Ochronosis: Bluish-black connective tissue, ear cartilage and sclerae
2. Urine turs black on prolonged exposure to air
3. Debilitating arthralgias!
134
Albinism is due to
Deficiency of tyrosinase: metabolising DOPA into melanin
135
HOMOCYstinuria findigns
1. Homocysteine in urine
2. Osteoporosis
3. Marfanoid habit
4. Ocular changed: lens subluxation
5. Cardiovascular effects
6. Kyphosis
7. Intellectual disability
136
Types of homocystinuria
1. Cystathione synthase deficiency
2. Lower affinity to cysthatione synthase for B6
3. Methionine synthase deficiency
137
What form of homocystinuria requires to rise levels of methionine in diet
Deficiency of methionine synthase
138
What form of homocystinuria requires to lower levels of methionine in diet, rise cysteine, B6 and B12?
Cystathione synthase deficiency
139
What form of homocystinuria requires to rise levels of B6 and cysteine in diet?
Lack of affinity of cystation synthase for B6
140
Cystinuria is due to?
Hereditary defect of renal PCT and intestinal Aa transporter that prevents reabsorption of Cysteine, Ornithine, Lysine and Arginine (COLA)
141
Treatment of cystinuria
Urinary Alkalinization and chelating agents increase solubility of cysteine stones
142
Diagnostic test for cystinuria
Urinary cyanide nitroprusside test
143
Glucagon and epinephrine: regulation on glycogen
1. Activate PKA
2. Activate glycogen phosphorylase kinase
3. Activate Glycogen phophorylase
4. Glucogenolysis
144
Insulin: regulation on glycogen
1. Binds to TK receptor
2. Activates protein phosphatase
3. Activates glycogen synthase
4. Glycogenesis
145
Bond in glycogen branches
alpha 1,6
146
Limit dextrin
One to four residues remaining on abranch after glycogen phosphorlylase has already shortened it
147
Type I glycogen storage disease
Von Gierke
148
Type II glycogen storage disease
Pompe disease
149
Type III glycogen storage disease
Cori disease
150
Type V glycogen storage disease
McArdle disease
151
Deficient Skeletal muscle glycogen phosphorylase
Myophosphorylae= Mc Ardle disease
152
Deficient Enzyme in Von Gierke disease
Glucose-6-phosphatase
153
Deficient debranching enzyme (glucogen storage diseases)
Cori disease
154
Findings in Von Gierke disease
```
Severe fasting hypoglycemia
Accumulates Glycogen in liver
High blood lactate
High triglycerides
High uric acid (gout)
Hepatomegaly
```
155
Lysosomal storage diseases
1. Tay-Sachs
2. Fabry
3. Metachromatic leukodystrophy
4. Krabbe
5. Gaucher
6. Nieman-Pick
7. Hurler syndrome
8. Hunter syndrome
156
Cherry red spot on macula
Tay Sachs
| Niemann-Pick
157
Hepatosplenomegly in Tay Sachs
No
158
Hepatosplenomegaly in Niemann-Pick
Yes
159
Deficient enzyme in tay-sachs
Hexosaminidase A (tAy-saX)
160
Angiokeratomas
Fabry disease
161
Triad in fabric disease
1. Angiokeratomas
2. Peripheral neuropathy
3. Hypohidrosis
162
Most common lysosomal storage disease
Gaucher
163
Lipid-laden macrophages resembling crumpled tissue paper
Gaucher cells
164
Gaucher disease findings
1. Hepatosplenomegaly
2. Pancytopenia
3. Osteoporosis
4. Avascular necrosis of femur
5. Bone cries
6. Gaucher cells
165
Nieman Pick disease finding
Progressive neurodegeneration: deffect in sphingomyelinase
166
Hurler syndrome- is there corneal clouding?
Yes
167
Hunter syndrome - is there corneal clouding?
No: hunters see clearly
168
X linked lysosomal storage diseases
Fabry
| Hunter: hunters aim for the X
169
Fatty acid synthesis requires transport of citrate from mitochondria to cytosol through
The citrate shuttle
170
Fatty acid degradation requires transport into the mitochondrial matrix through
Carnitine shuttle
171
Ketone bodies
Acetone
Acetoacetate
Beta hydroxybutyrate
172
Urine test for ketones detects
Acetoacetate
| NOT beta hydroxybutirate
173
Ketogenesis takes place in the _____ and uses ______ and _____ as substrates
Liver
Fatty acids
Amino acids
174
1g carb yields
4 kcal
175
1g alcohol yields
7 Kcal
176
1g fatty acid yields
9 Kcal
177
RBC use ketones
False, they lack mitochondria
178
Function of hormone sensitive lipase
Degradation of TG stored in adipocytes
179
Function of Lipoprotein Lipase
Deagradation of TG circulation in Qm and VLDL in vascular endothelial surface
180
Function of pancreatic lipase
Degradation of dietary triglycerides in small intestine
181
Apo E function
Mediates remnant uptake (everything except LDL)
182
Apo A-1 function
Activates LCAT
183
Apo C-2 function
Lipoprotein lipase cofactor that catalyzes cleavage
184
Apo B-48 function
Mediates chylomicron secretion into lymphatics
185
Apo B100 function
Binds to LDL receptor
186
Transports cholesterol from periphery to liver
HDL
187
Deficiency in Apo B48 and Apo B100
Abetalipoproteinemia
188
Findings in abetalipoproteinemia
```
Severe fat malabsorption
Steatorrhea
Failure to thrive
Retinitis pigmentosa!
Spinocerebellar degeneration: lack of vit E
Ataxia
Acanthocytosis
```
189
Treatment of abetalipoproteinemia
Middle chain fatty acids
| Oral vit E
190
Tuboeruptive xanthomas
III: dysbetalipoproteinemia: defective apo E
191
Hereditary hypertriglyciridemia
IV: hypertrygliceridemia: AD
192
Absent or defective LDL receptors
II: FAmilial hypercholesterolemia
193
Tendon achilles xanthomas
II: FAmilial hypercholesterolemia
194
Familial dyslipidemias
I: Hyperchylomicronemia
II:Familial hypercholesterolemia
III: Dysbetalipoproteinemia
IV: Hypertriglyceridemia
