Protein Synthesis:

Hutchinson-Gilford Progeria Syndrome

Diphtheria Toxin

Inhibitor
Streptomycin

GGC to GGT codon 608 of lamin A

gene
This change should be silent because
they both code for glycine
Activation of cryptic splice site
results in truncated lamin A with an
internal deletion of 50 amino acids
Accumulates farnesyl and obstructs
nuclear envelope
Disrupts transcription and translation
Premature aging
Failure to thrive and localized
scleroderma-like skin condition
Full body alopecia

Endotoxin synthesized by a
bacteriophage
o B subunit binds a cell surface
receptor facilitating the entry
of the A subunit to host Cell
o A subunit catalyzes the ADP
ribosylation of EF2 to inhibit
protein synthesis
Pharyngitis, fever, swelling of the
neck, and swollen skin lesions

Effect
Acting only on bacteria
Prevents the transition from initiation

Tetracycline
Erythromycin
Chloramphenicol

Puromycin

Actinomycin D

complex to chain elongating ribosome and

also causes miscoding
Blocks binding of aminoacyl-tRNA to A-site of
ribosome
Blocks the translocation reaction on
ribosomes
Blocks the peptidyl transferase reaction on
ribosomes
Acting on bacteria and eukaryotes
Causes the premature release of nascent
polypeptide chains by its addition to growin
chain end
Binds to DNA and blocks RNA polymerase

Liddle Syndrome

Autosomal Recessive Juvenile Parkinsonism

I-Cell disease (Mucolipidosis Type II)

Mutation in a subunit of the renal

epithelium sodium channel that
interferes with binding to its E3
ligase.
Accumulation of channel protein
results in excessive Na+ resorption
Hypertension
Abnormal kidney function

Mutation in the gene coding for protein

Parkin
Parkin is a ubiquitin E3 enzyme and results
in the accumulation of Parkin substrates
such as alpha synuclein, a protein
implicated in neuronal vesicle trafficking
Alzheimers
-

Intracellular inclusions
Lysosomal proteins not sorted
properly in Golgi
Defects due to mutation in the
enzyme
N-acetylglucosamine
phosphotransferase required for

attaching mannose-6-phosphate
Lysosome clogs
High prominent forehead, flattened
nose, narrow chest, slow development
Early death 8 years due to recurrent
respiratory infections and congested
heart failure

Glycogen Storage Diseases

GSD 1: Glucose 6-Phosphatase Deficiency
Von Gierke Disease

GSD 2: Lysosomal alpha-glucosidase

Pompe Disease

In liver blocks the final steps of

glycogenolytic and gluconeogenic
pathways
o Type 1A G6Pase catalytic
activity
o Type 1B and 1C defect in
translocase (transporter)
o Type 1D microsomal GLUT7
deficiency
Impairs ability of liver to produce
free glucose from glycogen and from
gluconeogenesis
Hypoglycemia, lactic acidosis,
hyperuricemia, hyperlipidemia
Doll like faces and protuberant
abdomen (Hepatomegaly and enlarged
kidneys)

Glycogen deposites accumulate in

lysosomes
Damage in muscle and nerves cells
Accumulation of glycogen in the

GSD 3: Debrancher Deficiency

Cori or Forbes Disease

GSD 5: Muscle Phosphorylase Deficiency

McArdle Disease

lysosome due to the deficiency of

lysosomal alpha-glucosidase enzyme
Infantile: Muscle hypotonia, cardiac
failure
Adult: limb-gridle, muscular
dystrophy-like features
Progressive accumulation causes
inflammation, fibrosis, and disruption
of contractile elements of muscle
Floppy baby

Amylo-1,6-glucosidase
Glycogen deposits have short outer
branches
o A (liver muscle)
o B (liver)
o C (muscle)
Fasting ketotic hypoglycemia,
hepatomegaly, short stature, variable
skeletal myopathy, and hyperthrophic
cardiomyopathy
Kidneys not enlarged
Muscle phosphorylase deficiency
(removes 1,4glycosyl residues from
outer branches of glycogen and adds
P to form G-1P)

GSD 6: Liver Phosphorylase Deficiency

Hers Disease

GSD 7: Muscle Phosphofructokinase

Deficiency
Tarui Disease

Exercise intolerance with muscle

cramps
Coca Cola urine due to rhabdomyolysis

Either phosphorylase b kinase

deficiency or protein kinase a
Hepatomegaly, mild hypoglycemia
Growth retardation
Glucose does not increase following
glucagon

GSD 11: Fanconi-Bickel Syndrome

Severe muscle cramps

Myoglobinuria
Hemolytic anemia

Defects in the facilitative glucose

transporter GLUT2 which transports
glucose in and out hepatocytes,
pancreatic B cells, and basolateral
memabranes of intestinal and renal
epithelial cells
Proximal renal tubular dysfunction,
impaired glucose and galactose
utilization and accumulation of
glycogen in liver and kidneys
Failure to thrive protuberant abdomen
(hepato and reno megaly)
Fat deposition in shoulders and
abdomen
Osteopenia

Glycogenesis
GSD 0: Liver Glycogen Synthase Deficiency

GSD 4: Branching Enzyme Deficiency

Amylopectinosis or Andersen Disease

Hypoglycemia and hyperketonemia

No hepatomegaly or hyperlipidemia
Rise in blood lactate

Failure to thrive
Hepatosplenomegaly
Cirrhosis
Myopathy (cardio)

A- deficiency of
phosphomannomutase which
converts mannose-6-p to mannose-1P

Congenital Disorders of Glycosylation

CDG 1A: N-glycosylation

CDG 1B: N-glycosylation

Inverted nipples
Abnormal deposition of fat pads

Phosphomannose isomerase
deficiency
Chronic diarrhea and cyclic vomiting
leading to failure to thrive
Hypoglycemia with abnormal high
insulin levels
Treated with mannose

Glycolisis Inhibitors
Inhibitor
Deoxy-beta-D-glucose
Iodoacetate/methyl mercuric chloride
Fluoride
Arsenate
Arsenite

Effect
GAPDH
Enolase
Competes with Pi for 1,3-BPG formation, and
produces less ATP
Forms stable complex with enzyme bound
lipoic acid

Lysosomal Storage Diseases

Fabrys Disease

Alpha-galactosidase A deficiency
Accumulation of
globotriasulceramide (GL-3)

Gauchers Disease

Peripheral neuropathy of hands/feet,

angiokeratomas, cardiovascular/renal
disease

Glucocerebrosidase deficiency leads

to macrophage engorgement
Hepatosplenomegaly, asepatic
necrosis of femur, bone crises,
Gauchers cells (macrophages that
look like crumpled tissure paper)
Symptoms are usually multisystemic,
often debilitating or disabling,
sometimes disfiguring, and can lead to
death.

Niemann-Pick Disease

Sphingomyelinase
Progressive neurodegeneration,
hepatosplenomegaly, cherry-red spot
on macula, foam cells

Tay-Sachs Disease

Hexosaminidase
Progressive neurodegeneration,
developmental delay, cherry-red spot
on macula, lysosomes with onion skin,
no hepatosplenomegaly (vs. NiemannPick)

Krabbes Disease

Galactocerebrosidase
Peripheral neuropathy, developmental
delay, optic atrophy, globoid cells

Metachromatic Leukodystrophy

Arylsulfatase A
Central and peripheral demyelination

with ataxia, dementia

Hurlers Syndrome MPS1

Hunters Syndrome MPS2

Alpha-L-iduronidase enzyme
deficiency
Developmental delay, gargoylism,
airway obstruction, corneal clouding,
hepatosplenomegaly
Carpal tunnel syndrome (claw hands),
skeletal deformities

Iduronate-2-sulfatase enzyme
deficiency
Accumulation of glycosaminoglycans
(GAG)
Mild Hurlers + aggressive behavior, no
corneal clouding
Bone dysplasia, cognitive impairment,
cardiac disease, frequent pulmonary
problems, hepatosplenomegaly