Clinical Correlations

Question 1

Errors during these processes can lead to dysfunctional proteins

Answer 1

Replication

Transcription

Translation

Question 2

Mode of action of Streptomycin

Answer 2

mRNA is misread so no inititiation complex is made

Question 3

Mode of action of tetracycline

Answer 3

Inhibition of binding of aminoacyl-tRNA to the A site

Question 4

What is the mode of action of chloramphenicol?

Answer 4

Inhibition of peptidyl transferase activity so elongation is affected

Question 5

Mode of action of Erythromycin

Answer 5

Inhibition of translocation of the peptidyl-tRNA to the P site

Question 6

Mode of action of neomycin/gentamycin

Answer 6

Mistranslation of the mRNA codon so incorrect aa-tRNAs incorporated and effects initiation

Question 7

What is gray baby syndrome?

Answer 7

An adverse reaction to chloramphenicol where mitochondrial ribosomes are mistakenly attacked over the procaryotic ribosomes. Leads to ashen grey skin, blue lips, and blue nail beds.

Question 8

What does diptheria toxin target and what are the symptoms?

Answer 8

Targets eukaryotic elongation factor 2 (eEF-2) by ADP-ribosylation

Lesions in upper respiratory tract cause necrotic injury to epithelial cells

Question 9

Targets 28S rRNA and cleaves adenine base from it. Cleavage impacts N-glycosidase activity and a loss of binding of elongation factors to large ribosomal subunit. Protein synthesis is off

Answer 9

Ricin

Question 10

Disorder in collagen processing. Mutations in ATPase copper transporting gene and impacts lysine hydroxylase. Patients present with depigmented hair and hypotonia

Answer 10

Menkes Disease

Question 11

I-cell Disease

Answer 11

Transfer of a phosphate to mannose during post translational modification of lysosomal enzymes is impaired. Lysosomal enzymes are unable to enter the lysosome and are secreted in serum. Lysosomes are dysfunctional

Patients present with inclusion bodies in fibroblasts, coarse facial features, and bone fractures and slow motor abilities

Question 12

Cystic Fibrosis

Answer 12

Mutations in gene encoding chloride channel membrane protein (CFTR) which causes disorder in N-linked glycosylation and misfolding of CFTR.

Stickiness of fluids. Symptoms are cough, repeated lung infections, and damaged pancreas

Question 13

Alpha 1 Antitrypsin Deficiency

Answer 13

Alpha 1 Antitrypsin is expressed in liver. Deficiency results in mutations of gene encoding alpha 1 antitrypsin protein, which causes misfolding of the protein and aggregations of it in the ER. This damages the liver cell. Parents with M allele do not develop the disease

Symptoms are liver cyrrhosis and chronic pulmonary disease due to lack of alpha1-antitrypsin

Question 14

Alcohol Tolerance

Answer 14

Prolonged alcohol or barbiturate use lead to increase of SER which means more enzymes and faster metabolism. Need more alcohol or drugs to get same effect

Question 15

Proton Leak

Answer 15

Protons re-enter mitochondrial matrix without contributing to ATP synthesis. In most cells it is problematic and wastes energy and creates free radicals (ROS) that damage mitochondria and cell.

Intentional proton leak in brown fat cells, mediated by uncoupling protein called thermogenin to drive non-shivering thermogenesis

Question 16

Tay-Sachs Disease

Answer 16

Lysosomal Storage Disease. Enzyme required for break down of gangliosides is malformed so gangliosides accumulate in CNS neurons.

Question 17

Zellweger Syndrome

Answer 17

Mutation in gene encoding receptor for peroxisomal targeting signal. Shipping label to peroxisome is correct but receptor in peroxisomal membrane can’t read it.

Results in severe neurologic dysfunction and craniofacial abnormalities and liver dysfunction

Question 18

Patient presents with pellagra (dermatitis, diarrhea, dementia) and does not have eat beans, milk, eggs, or enriched flour. Patient also has alcohol use disorder. What are they deficient in?

Answer 18

Niacin - Vitamin B3

Question 19

Patient presents with sore mouth. Smooth, swollen, magenta tonuge with stomatitis and cheilosis. What are they deficient in?

Answer 19

Riboflavin - Vitamin B2

Question 20

Hemoglobin A1c

Answer 20

Early glycation product. Measures the amount of glucose attached to hemoglobin in red blood cells.

Question 21

Why can bacteria digest polysaccharides like cellulose?

Answer 21

Bacteria can break the Beta 1,4 linked glucose

Question 22

Lactose Intolerance

Answer 22

Lactase non-persistance.

Patient will present with recurring abdominal pain for duration of 4 months and occurs when they eat at favorite ice cream shop. After lactose ingestion, pt does not have rise in blood sugar, H2 detectable in breath, and they have acidic stool

Question 23

Raffinose

Answer 23

Rich in legumes. Has alpha 1,6 galactosidic bond and can’t be digested. Supplements for galactosidase can help

Question 24

How does a patient present with a glycolytic disorder?

Answer 24

Hemolytic anemia

Jaundice

Enlarged spleen

Rare congenital disorders

Occurs because red blood cells rely exclusively on glycolysis

Question 25

Mutations in genes for enzymes specialized for glycolytic degradation

Answer 25

Inherited Errors of Metabolism Disorder present at birth and manifest when offending substance ingested. IEM impede development and need to be addressed early to prevent disability

Question 26

Essential Fructosuria

Answer 26

Fructokinase deficiency, fructose excreted in urine. Benign

Question 27

Hereditary Fructose Intolerance

Answer 27

Aldolase B deficiency Fructose-phosphate accumulates in liver Depletes liver phosphate pools and impairs glycogen mobilization - hypoglycemia Liver damaged with accumulation of glycogen and lack of phosphate for synthesis of ATP - jaundice Treat by avoiding fructose and sucrose

Question 28

Galactosemia

Answer 28

Galactose Metabolism Disorder Many types - Galactose 1 phophate uridyl transferase deficiency - UDP galactose epimerase deficiency - Galactokinase deficiency Affected newborns present with milk intolerance and signs of liver failure (jaundice)

Question 29

Thiamine deficiency

Answer 29

Common in alcoholic patients because alcoholism inhibits thiamine uptake and conversion to TPP.

Question 30

Beri Beri

Answer 30

Thiamine Deficiency Patients present with pain and paresthesia. Wet form present with symptoms of congestive heart failure. Dry form presents with symmetric peripheral neuropathy

Question 31

Wernicke Encephalopathy

Answer 31

Thiamine deficiency in chronic alcoholism patient. CNS impacted via mental impairment, cerebellar ataxia, horizontal nystagmus, and opthalmoplegia. Treat with administration of thiamine. Can progress to Wernicke-Korsakoff syndrome

Question 32

Pyruvate dehydrogenase deficiency

Answer 32

Patient present with unexplained metabolic acidosis. Homozygous mutation in PDHX gene which encodes the E3 binding protein. The binding protein is important for the function of PDH. Patient placed on high fat diet and limit carbohydrates Most common mutations impact pyruvate decarboxylase (E1)

Question 33

Fumarase deficiency

Answer 33

Elevated urinary fumarate because fumarase converts fumarate to malate. Very rare

Question 34

DNP

Answer 34

Potent uncoupling agent used for dieting. Works by collapsing proton gradient and bypassing ATP synthase.

Question 35

What are inhibitors of electron transport chain?

Answer 35

Anoxia - no oxygen, no oxidative phosphorylation Rotenone - inhibits complex I so e- can be moved from NADH to coenzyme Q Antimycin A - inhibits complex III so electrons not transferred from coenzyme Q to cytochrome c Cyanide - Inhibits complex IV and binds heme iron. Blocks transfer of electrons from cytochrome c to oxygen

Question 36

Mitochondrial Encephalomyopathies

Answer 36

Defects in oxidative phosphorylation MERRF - Associated with ragged red fibers. Due to point mutations in mitochondrial tRNA for lysine MELAS - Mutation in mitochondrial gene encoding tRNA for leucine. Combined oxidative phosphorylation deficiency 1 - mutation in mitochondrial elongation factor 1 gene Combined oxidative phosphorylation deficiency 2 - mutation in mitochondrial ribosomal protein S16

Question 37

Leber hereditary optic neuropathy

Answer 37

Mutation in genes that affect complex I of respiratory chain Optic nerve dies and pt has sudden onset loss of vision.

Question 38

Gluconeogenesis Disorder

Answer 38

Example: Fructose 1,6 bisphosphatase deficiency Patient presents with fasting hypoglycemia Metabolic acidosis Abnormal glucagon response - no sign. increase in blood glucose Liver stores fat instead of carbs

Question 39

How will a patient with a Pentose Phosphate Pathway Disorder present?

Answer 39

Hemolytic anemia - red blood cells lack NADPH Jaundice Enlarged spleen

Question 40

Glucose 6-Phosphate Dehydrogenase Deficiency

Answer 40

Most common in Mediterranean and African Americans. Affects more males (X-linked) Depletes RBCs of NADPH which lowers radical stress resistance. Hemolytic anemia

Question 41

Glycogen Storage Diseases

Answer 41

Liver and muscle can have glycogen phosphorylase defects Liver can have glucose 6 phosphatase deficiency All tissues can have alpha-glucosidase defect since all tissues perform autophagy

Question 41

Patient present with muscle pain, fever and dark urine. They have exercise intolerance and muscles show hypertrophy and elevation levels of glycogen and absent glycogen phosphorylase activity. No production of lactate in exercise.

Answer 41

Patient cannot mobilize intracellular glucose reserves during exercise.

Question 42

Glycogen Storage Disease affecting the liver and is glucose 6-phosphatase deficiency

Answer 42

Type 1: Von Gierke Patient presents with fasting hypoglycemia and enlarged liver. Glucose 6-phosphate builds up,

Question 43

glycogen storage disease affecting all tissues. Involves acid maltase (lysosomal alpha glucosidase deficiency)

Answer 43

Type II: Pompe Lysosomal storage disease that causes enlarged liver and heart.

Question 44

Glycogen Storage Disease affecting muscle only. Involves muscle glycogen phosphorylase deficiency.

Answer 44

Type V: McArdle Muscle unable to mobilize glycogen and results in exercise intolerance. Muscle cramps, fatigue, and burgundy urine.

Question 45

What metabolic reactions occur with epinephrine?

Answer 45

Increase muscle ATP production Signaling through cAMP and calcium Liver gluconeogenesis and glycogenolysis increases Muscle glycolysis also increases

Question 46

What metabolic reactions occurs with increased cortisol?

Answer 46

Increase glucose supply. Change gene transcription. Liver gluconeogenesis and glycogen synthesis increase Glucose deposition in adipose tissues decreases

Question 47

How does a patient with alcohol use disorder present?

Answer 47

Fasting hypoglycemia Metabolic Acidosis Fatty liver - impairs uptake and storage of vitamins of carb metabolism (wernicke korsakoff and beri beri)

Question 48

Hunter Syndrome

Answer 48

Mucopolysaccharidoses X-linked disorder and patient presents with skeletal abnoramalities and intellectual disability

Question 49

Hurler-Scheie Syndrome

Answer 49

Mucopolysaccharidoses Elevated urine glycosaminoglycan. Defective alpha iduronidase enzyme. Inability to degrade dermatan and heparan sulfate. Results in skeletal abnormalities and intellectual disability.

Question 50

Sanfilippo Syndrome

Answer 50

Mucopolysaccharidoses Mild defects

Question 51

What will low UDP-UGT activity result in?

Answer 51

Patient will have inability to transfer glucuronic acid which causes buildup of molecules like bilirubin. Bilirubin UGT defects cause non-hemolytic jaundice Gilbert Syndrome - most common Crigler Najjar Syndrome - severe