• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/694

Click to flip

694 Cards in this Set

  • Front
  • Back
Full-term neonate of uneventful
delivery becomes mentally
retarded and hyperactive and
has a musty odor.
PKU.
Stressed executive comes
home from work, consumes 7
or 8 martinis in rapid succession
before dinner, and becomes
hypoglycemic. mech?
NADH increase prevents
gluconeogenesis by shunting
pyruvate and oxaloacetate to
lactate and malate.
2-year-old girl has an ↑ in
abdominal girth, failure to thrive, and skin and hair depigmentation.
Kwashiorkor.
Alcoholic develops a rash,
diarrhea, and altered mental
status.
low Vitamin B3 (pellagra).
51-year-old man has black spots
in his sclera and has noted that
his urine turns black upon
standing.
Alkaptonuria.
25-year-old male complains
of severe chest pain and has
xanthomas of his Achilles
tendons.
Familial hypercholesterolemia;
A woman complains of intense
muscle cramps and darkened
urine after exercise.
McArdle’s disease.
Two parents with albinism
have a son who is normal. . how
Locus heterogeneity.
A 40-year-old man has chronic
pancreatitis with pancreatic
insufficiency. What vitamins are likely deficient?
A, D, E, and K.
Vitamins

name the fat solubles
and quick functions
Vitamin A—Vision
Vitamin D—Bone calcification
—Ca2+ homeostasis
Vitamin K—Clotting factors
Vitamin E—Antioxidant
Vitamins

name the water solubles with aka's
B1 (thiamine: TPP)
B2 (riboflavin: FAD, FMN)
B3 (niacin: NAD+)
B5 (pantothenate: CoA)
B6 (pyridoxine: PP)
B12 (cobalamin)
C (ascorbic acid)
Biotin
Folate
Vitamins: water
soluble

All wash out easily from body
except
B12 and folate
B-complex deficiencies often
result in
dermatitis,
glossitis, and diarrhea.
Vitamin A
aka
retinol
Vitamin A (retinol)

Deficiency
Night blindness, dry skin. increased suceptability to measles
Vitamin A (retinol)

Function
Constituent of visual pigments (retinal).
Vitamin A (retinol)

Excess
Arthralgias, fatigue, headaches, skin changes, sore throat, alopecia.
retinol
aka
Vitamin A
Vitamin A (retinol)

source
Found in leafy vegetables.
Vitamin A (retinol)

mnemonioc
Retinol is vitamin A, so think
Retin-A (used topically for
wrinkles and acne).
Vitamin B
aka
thiamine
thiamine
aka
Vitamin B
Vitamin B1 (thiamine)

Deficiency
Beriberi and Wernicke-Korsakoff syndrome. Seen in alcoholism and malnutrition.
Spell beriberi as Ber1Ber1.
Vitamin B1 (thiamine)

Function
In thiamine pyrophosphate, a cofactor for oxidative
decarboxylation of α-keto acids (pyruvate,
α-ketoglutarate) and a cofactor for transketolase in the HMP shunt.
Dry beriberi
vs
Wet beriberi
Dry beriberi––polyneuritis,
muscle wasting.
Wet beriberi––high-output
cardiac failure (dilated
cardiomyopathy), edema.
Vitamin B2
aka
riboflavin
riboflavin
aka
Vitamin B2
Vitamin B2 (riboflavin)

Deficiency
The 2C’s.

Angular stomatitis, Cheilosis, Corneal vascularization.
Vitamin B2 (riboflavin)

Function
Cofactor in oxidation and reduction (e.g., FADH2).

"FAD and FMN are derived from
riboFlavin (B2 = 2 ATP)"
Vitamin B3
aka
niacin
niacin
aka
Vitamin B3
Vitamin B3 (niacin)

Deficiency
Pellagra can be caused by Hartnup disease (↓ tryptophan absorption), malignant carcinoid syndrome (↑ tryptophanmetabolism), and INH (↓ vitamin B6).

Pellagra’s symptoms are the 3 D’s: Diarrhea, Dermatitis,
Dementia (also beefy
glossitis).
Vitamin B3 (niacin)

Function
Constituent of NAD+, NADP+ (used in redoxreactions). Derived from tryptophan using vitamin B6.

NAD derived from Niacin
(B3 = 3 ATP).
Diarrhea, Dermatitis,
Dementia (also beefy
glossitis).
Pellagra
Pellagra’s symptoms
the 3 D’s: Diarrhea, Dermatitis,
Dementia (also beefy
glossitis).
pantothenate
aka
Vitamin B5
Vitamin B5
aka
pantothenate
Vitamin B5 (pantothenate)
Deficiency
Dermatitis, enteritis, alopecia, adrenal insufficiency.
Vitamin B5 (pantothenate)

Function
Constituent of CoA (a cofactor for acyl transfers)
and component of fatty acid synthase.

Pantothen-A is in Co-A.
pyridoxine
aka
Vitamin B6
Vitamin B6
aka
pyridoxine
Vitamin B6 (pyridoxine)

Deficiency
Convulsions, hyperirritability (deficiency inducible by INH and oral contraceptives),
peripheral neuropathy.
Vitamin B6 (pyridoxine)

Function
Converted to pyridoxal phosphate, a cofactor used in transamination (e.g., ALT and AST),
decarboxylation, and heme synthesis.
Vitamin B12
aka
cobalamin
cobalamin
aka
Vitamin B12
Vitamin B12 (cobalamin)

Deficiency
Macrocytic, megaloblastic anemia; neurologic
symptoms (optic neuropathy, subacute combined
degeneration, paresthesia); glossitis.
Function
Cofactor for homocysteine methylation
(transfers CH3 groups as methylcobalamin)
and methylmalonyl-CoA handling.
Vitamin B12 (cobalamin)

source and storage
Found only in animal products.

Stored primarily in the liver.
Very large reserve pool (several years).
Vitamin B12 (cobalamin)

causes of deficiency
Vitamin B12 deficiency is
usually caused by
malabsorption (sprue,
enteritis, Diphyllobothrium
latum), lack of intrinsic factor (pernicious anemia), or absence of terminal ileum
(Crohn’s disease).
Vitamin B12 (cobalamin)

testing
Use Schilling test to detect
deficiency.
Vitamin B12 (cobalamin)

syntesized by
Synthesized only by microorganisms.
schilling test rocess
the patient is given radiolabeled vitamin B12 to drink A normal result shows at least 5% of the radiolabelled vitamin B12 in the urine over the first 24 hours.
Folic acid

Deficiency
Macrocytic, megaloblastic anemia (often no neurologic symptoms, as opposed to vitamin B12 deficiency).
Folic acid

Function
Coenzyme (tetrahydrofolate) for 1-carbon
transfer; involved in methylation reactions.
Important for the synthesis of nitrogenous bases
in DNA and RNA.
Folic acid

source
FOLate from FOLiage.
what is PABA and implications
PABA is the folic acid
precursor in bacteria. Sulfa
drugs and dapsone
(antimicrobials) are PABA
analogs.
the folic acid
precursor in bacteria
PABA
Most common vitamin deficiency in the United
States.
Folic acid
Biotin

Deficiency
Dermatitis, enteritis. Caused by antibiotic use,
ingestion of raw eggs.

“AVIDin in egg whites
AVIDly binds biotin.”
Biotin

Function
Cofactor for carboxylations:
1. Pyruvate → oxaloacetate
2. Acetyl-CoA → malonyl-CoA
3. Proprionyl-CoA → methylmalonyl-CoA
Vitamin C (ascorbic acid)

Deficiency
Scurvy––swollen gums, bruising, anemia, poor wound healing.
Vitamin C (ascorbic acid)


Function
Necessary for hydroxylation of proline and lysine in
collagen synthesis.
Facilitates iron absorption by keeping iron in Fe+2
reduced state (more absorbable)
Necessary as a cofactor for dopamine →NE.
Vitamin C (ascorbic acid)

role in collagen formation
Vitamin C Cross-links
Collagen. Necessary for hydroxylation of proline and lysine in collagen synthesis.
Vitamin D

different forms and locations
D2 = ergocalciferol, consumed in milk.
D3 = cholecalciferol, formed in sun-exposed skin.
25-OH D3 = storage form.
1,25 (OH)2 D3 = active form.
Vitamin D

Deficiency
Rickets in children (bending bones), osteomalacia
in adults (soft bones), and hypocalcemic tetany.
Vitamin D

Function
↑ intestinal absorption of calcium and phosphate.
Vitamin D

Excess
Hypercalcemia, loss of appetite, stupor. Seen in
sarcoidosis, a disease where the epithelioid
macrophages convert vitamin D into its active form.
Vitamin E

Deficiency
Increased fragility of erythrocytes, neurodysfunction.

Vitamin E is for Erythrocytes.
Vitamin E

Function
Antioxidant (protects erythrocytes from hemolysis).

Vitamin E is for Erythrocytes.
Vitamin K

Deficiency
Neonatal hemorrhage with ↑ PT and ↑ aPTT but normal bleeding time,
Vitamin K

Function
Catalyzes γ-carboxylation of glutamic acid residues
on various proteins concerned with blood clotting.
Vitamin K

Deficiency
who is most vulnerable and why
because neonates have sterile intestines and are unable to synthesize
vitamin K.
Vitamin K

source
Synthesized by intestinal flora. Therefore, vitamin
K deficiency can occur after the prolonged use of
broad-spectrum antibiotics.
the vitamin K–dependent
clotting factors are
II, VII, IX, X,
Zinc

deficiency
Delayed wound healing, hypogonadism, ↓ adult hair (axillary, facial, pubic); may
predispose to alcoholic cirrhosis.
Delayed wound healing, hypogonadism, ↓ adult hair (axillary, facial, pubic); may
predispose to alcoholic cirrhosis.
Zinc

deficiency
Night blindness, dry skin.
Vitamin A (retinol)
Deficiency
Beriberi and Wernicke-Korsakoff syndrome
Vitamin B1 (thiamine)
Deficiency
A, D, E, K. Absorption dependent on
gut (ileum) and pancreas.
Angular stomatitis, Cheilosis, Corneal
vascularization.
Vitamin B2 (riboflavin)

Deficiency
Dermatitis, enteritis, alopecia, adrenal insufficiency.
Vitamin B5 (pantothenate)

Deficiency
Convulsions, hyperirritability (deficiency inducible by INH and oral contraceptives),
peripheral neuropathy.
Vitamin B6 (pyridoxine)

Deficiency
Macrocytic, megaloblastic anemia; neurologic
symptoms (optic neuropathy, subacute combined
degeneration, paresthesia); glossitis.
Vitamin B12 (cobalamin)

Deficiency
Macrocytic, megaloblastic anemia (often no
neurologic symptoms, as opposed to vitamin
B12 deficiency).
Folic acid

Deficiency
Dermatitis, enteritis. Caused by antibiotic use,
Biotin

Deficiency
Increased fragility of erythrocytes, neurodysfunction.
Vitamin E
Deficiency
Ethanol metabolism

limiting reagent
NAD+ is the limiting reagent.
Disulfiram (Antabuse)

mech
inhibits acetaldehyde dehydrogenase (acetaldehyde accumulates, contributing to hangover symptoms).
Disulfiram
aka
Antabuse
Antabuse
Disulfiram
Ethanol hypoglycemia

mech
Ethanol metabolism ↑ NADH/NAD+ ratio in liver, causing diversion of pyruvate to lactate and OAA to malate, thereby inhibiting gluconeogenesis
fatty change mech
↑ NADH/NAD+ ratio in liver with shunting away from glycolysis and toward fatty acid synthesis
Kwashiorkor

causes
Kwashiorkor results from a
protein-deficient MEAL:
Malabsorption
Edema
Anemia
Liver (fatty)
Kwashiorkor
protein malnutrition resulting in skin
lesions, edema, liver malfunction (fatty change).
Clinical picture is small child with swollen belly.
protein malnutrition resulting in skin lesions, edema, liver malfunction (fatty change).
Clinical picture is small child with swollen belly.
Kwashiorkor
Marasmus
energy malnutrition resulting in
tissue and muscle wasting, loss of subcutaneous
fat, and variable edema.
energy malnutrition resulting in
tissue and muscle wasting, loss of subcutaneous
fat, and variable edema.
Marasmus
Chromatin
structure
(−) charged DNA loops twice around nucleosome
core (2 each of the (+) charged H2A, H2B, H3,
and H4) to form nucleosome bead.H1 ties nucleosomes together in a string (30-nm
fiber).
the only histone that is not
in the nucleosome core.
H1 is
H1 is
the only histone that is not
in the nucleosome core.
Heterochromatin
Condensed, transcriptionally inactive Chromatin
Condensed, transcriptionally inactive Chromatin
Heterochromatin
Less condensed, transcriptionally active Chromatin
Euchromatin
Euchromatin
Less condensed, transcriptionally active Chromatin
Nucleotides

ring number
Purines (A, G) have 2 rings. Pyrimidines (C, T, U)
have 1 ring.
Deamination of ???? makes uracil.
cytosine
Deamination of cytosine makes ????.
uracil.
Amino acids necessary for purine
synthesis:
Glycine
Aspartate
Glutamine
which Nucleotide

has a methyl
Thymine
which Nucleotide

has a ketone
Guanine
Nucleotides
which are which
-Purines (A, G) PURe As Gold: PURines.

-Pyrimidines (C, T, U) CUT the PY (pie): PYrimidines.
Nucleotides (base + ribose + phosphate) are linked by
3′-5′ phosphodiester bond.
Nucleotides are made of what three things
base + ribose + phosphate
Nucleotides
Transition vs. transversion
Transition-Substituting purine for purine or pyrimidine for
pyrimidine. ( TransItion = Identical type.)

Transversion Substituting purine for pyrimidine or visa versa. (TransVersion = conVersion between types).
Genetic code features and exceptions

Unambiguous
Each codon specifies only one amino acid.

no exceptions
Genetic code features and exceptions

Degenerate/redundant
More than one codon may code for the same
amino acid.

Methionine encoded by only
one codon.
Genetic code features and exceptions

Commaless, nonoverlapping
Read from a fixed starting point as a continuous
sequence of bases.

Some viruses are an exception.
Genetic code features and exceptions

Universal
Genetic code is conserved throughout evolution.

Exceptions include
mitochondria, archaebacteria,
Mycoplasma, and some yeasts.
Mutations in DNA

Silent
Same aa, often base change in 3rd position of
codon (tRNA wobble).
Mutations in DNA

Same aa, often base change in 3rd position of
codon (tRNA wobble).
Silent
Mutations in DNA

Missense
Changed aa (conservative––new aa is similar
in chemical structure).
Mutations in DNA

Changed aa (conservative––new aa is similar in chemical structure).
Missense
Mutations in DNA

Nonsense
Change resulting in early stop codon.
Mutations in DNA

Change resulting in early stop codon.
Nonsense
Mutations in DNA

Frame shift
Change resulting in misreading of all nucleotides
downstream, usually resulting in a truncated
protein.
Mutations in DNA

Change resulting in misreading of all nucleotides
downstream, usually resulting in a truncated
protein.
Frame shift
point Mutations in DNA

Severity of damage
Severity of damage: nonsense
> missense > silent.
DNA replication and DNA polymerases

who has multiple origins of
replication.
Eukaryotic genome
DNA replication and DNA polymerases

Eukaryotes Replication begins at
Replication begins at a consensus sequence of
AT-rich base pairs.
DNA replication and DNA polymerases

who has Single origin of replication
Prokaryotes
DNA replication and DNA polymerases

Create a nick in the helix to
relieve supercoils.
DNA
topoisomerases
DNA replication and DNA polymerases


function/activity of DNA
topoisomerases
Create a nick in the helix to
relieve supercoils.
DNA replication and DNA polymerases

Makes an RNA primer on which DNA
polymerase III can initiate replication.
Primase
DNA replication and DNA polymerases


function/activity of Primase
Makes an RNA primer on which DNA
polymerase III can initiate replication.
DNA replication and DNA polymerases

Elongates the chain by adding
deoxynucleotides to the 3′ end until it reaches
primer of preceding fragment. 3′→ 5′
exonuclease activity “proofreads” each added
nucleotide.
DNA polymerase
III
DNA replication and DNA polymerases


function/activity of DNA polymerase
III
Elongates the chain by adding
deoxynucleotides to the 3′ end until it reaches
primer of preceding fragment. 3′→ 5′
exonuclease activity “proofreads” each added
nucleotide.
DNA replication and DNA polymerases

Degrades RNA primer and fills in the gap
with DNA.
DNA polymerase I
DNA replication and DNA polymerases


function/activity of DNA polymerase I
Degrades RNA primer and fills in the gap
with DNA.
DNA replication and DNA polymerases

Seals.
DNA ligase
DNA replication and DNA polymerases

function/activity of DNA ligase
Seals.
??????? has
5′→ 3′ synthesis and
proofreads with 3′→ 5′
exonuclease.
DNA polymerase III
??????? excises
RNA primer with 5′→ 3′
exonuclease.
DNA polymerase I
DNA repair

Nucleotide excision
repair
Specific endonucleases release the oligonucleotide-
containing damaged bases; DNA polymerase and
ligase fill and reseal the gap, respectively.
DNA repair

Specific endonucleases release the oligonucleotide-
containing damaged bases; DNA polymerase and
ligase fill and reseal the gap, respectively.
Nucleotide excision
repair
DNA repair

Base excision repair
Specific glycosylases recognize and remove damaged
bases, AP endonuclease cuts DNA at apyrimidinic
site, empty sugar is removed, and the gap is filled
and resealed.
DNA repair

Specific glycosylases recognize and remove damaged
bases, AP endonuclease cuts DNA at apyrimidinic
site, empty sugar is removed, and the gap is filled
and resealed.
Base excision repair
DNA repair

mutation in Nucleotide excision
repair
Mutated in xeroderma
pigmentosa (dry skin with
melanoma and other cancers).
DNA repair

mutation in xeroderma
pigmentosa
Nucleotide excision
repair
DNA repair

Base excision repair
Specific glycosylases recognize and remove damaged
bases, AP endonuclease cuts DNA at apyrimidinic
site, empty sugar is removed, and the gap is filled
DNA repair

Specific glycosylases recognize and remove damaged
bases, AP endonuclease cuts DNA at apyrimidinic
site, empty sugar is removed, and the gap is filled
Base excision repair
Mismatch repair
Unmethylated, newly synthesized string is recognized, M
mismatched nucleotides are remove, and the gap is
filled and resealed.
DNA repair

Unmethylated, newly synthesized string is recognized, M
mismatched nucleotides are remove, and the gap is
filled and resealed.
Mismatch repair
DNA repair

Mutation in hereditary
nonpolyposis colon cancer.
Mismatch repair
DNA repair

Nonhomologous
end joining
Brings together two ends of DNA fragments. No requirement for homology.
DNA repair

Brings together two ends of DNA fragments. No requirement for homology.
Nonhomologous
end joining
DNA/RNA
synthesis direction
DNA and RNA are both synthesized 5′→ 3′.
Remember that the 5′ of the incoming nucleotide
bears the triphosphate (energy source for bond).
The 3′ hydroxyl of the nascent chain is the target.
protein synth
synthesis direction
Protein synthesis also proceeds
in the 5′ to 3′ direction.
Amino acids are linked
N to C.
Types of RNA
and descriptions
Massive, Rampant, Tiny.

mRNA is the largest type of RNA.
rRNA is the most abundant type of RNA.
tRNA is the smallest type of RNA.
RNA polymerases

Eukaryotes
I,II,III
RNA polymerase I makes rRNA.
RNA polymerase II makes mRNA.
RNA polymerase III makes tRNA.
RNA polymerases

Prokaryotes
RNA polymerase (multisubunit complex) makes
all 3 kinds of RNA.
α-amanitin
found in death cap mushrooms.

inhibits RNA polymerase II.
found in death cap mushrooms.

inhibits RNA polymerase II.
α-amanitin
RNA polymerases

proofreading
No proofreading function, but can initiate chains.
???? opens DNA at promoter site
RNA polymerase II opens DNA at promoter site
mRNA initiation
codons
AUG (or rarely GUG).

AUG inAUGurates protein
synthesis.
mRNA stop codons
UGA = U Go Away.
UAA = U Are Away.
UAG = U Are Gone.
Promoter
Site where RNA polymerase and multiple other
transcription factors bind to DNA upstream from
gene locus (AT-rich upstream sequence with
TATA and CAAT boxes).
Site where RNA polymerase and multiple other
transcription factors bind to DNA upstream from
gene locus (AT-rich upstream sequence with
TATA and CAAT boxes).
Promoter
Stretch of DNA that alters gene expression by binding
transcription factors. May be located close to, far
from, or even within (in an intron) the gene whose
expression it regulates.
Enhancer
Enhancer
Stretch of DNA that alters gene expression by binding
transcription factors. May be located close to, far
from, or even within (in an intron) the gene whose
expression it regulates.
Promoter mutation commonly
results in
dramatic ↓ in
amount of gene transcribed.
Site where negative regulators (repressors) bind.
Operator
Operator
Site where negative regulators (repressors) bind.
Introns vs.
exons
Exons contain the actual genetic information coding for protein.
Introns are intervening noncoding segments of DNA.
Splicing of mRNA

steps
➀ Primary transcript combines with snRNPs to form spliceosome.
➁ Lariat-shaped intermediate is generated.
➂ Lariat is released to remove intron precisely and join two exons.
RNA processing
(eukaryotes)

where
Occurs in nucleus. After transcription:
RNA processing
(eukaryotes)

steps
1. Capping on 5′ end (7-methyl-G)
2. Polyadenylation on 3′ end (≈ 200 A’s)
3. Splicing out of introns
RNA processing
(eukaryotes)

names
Initial transcript is called heterogeneous nuclear
RNA (hnRNA).
Capped and tailed transcript is called mRNA.
Only ???????? RNA is
transported out of the
nucleus.
processed
RNA processing
(eukaryotes)

wrt transport
Only processed RNA is
transported out of the
nucleus.
tRNA
Structure
75–90 nucleotides, cloverleaf form, anticodon end is opposite 3′ aminoacyl end. All
tRNAshave CCA at 3′ end where aa's are bound
tRNA Charging
Aminoacyl-tRNA synthetase (1 per aa, uses ATP)
where is error protection in protein synthesis
in TRNA charging. once aa is on there it will put on a wrong aa
Protein synthesis

Initiation
Initiation factors (IFs) help assemble the 30S
ribosomal subunit with the initiator tRNA, are
released when the mRNA and the ribosomal
subunit assemble with the complex.
Protein synthesis

elongation steps
1. Aminoacyl tRNA binds to A site.
2. Peptidyltransferase catalyzes peptide bond
formation, transfers growing polypeptide to ami
acid in A site.
3. Ribosome advances three nucleotides toward 3′
end of RNA, moving peptidyl RNA to P site.
Protein synthesis

A site
A site = incoming Aminoacyl
tRNA.
Protein synthesis

P site
P site = accommodates growing
Peptide.
Protein synthesis

E site
E site = holds Empty tRNA as
it Exits.
Protein synthesis

ATP vs GTP
ATP—tRNA Activation
(charging).
GTP—tRNA Gripping and
Going places (translocation).
Posttranslational modifications

Trimming
Removal of N- or C-terminal pro-peptides from zymogens to generate mature proteins.
Posttranslational modifications

Covalent alterations
Phosphorylation, glycosylation, and hydroxylation.
Posttranslational modifications

Proteasomal degradation
Attachment of ubiquitin to defective proteins to tag them for breakdown.
Cell cycle phases

shortest phase
Mitosis
Cell cycle phases

Permanent cells what and examples
Remain in G0, regenerate from stem cells.

Never go to G0, divide rapidly with a short G1.
Cell cycle phases

Stable cells what and examples
Enter G1 from G0 when stimulated.

Hepatocytes, lymphocytes.
Cell cycle phases

Labile cells what and examples
Never go to G0, divide rapidly with a short G1.

Bone marrow, gut epithelium,
skin, hair follicles.
Checkpoints control
transitions between
phases. Regulated by
cyclins, cdks, and
tumor suppressors.
RER is the site of
synthesis of secretory (exported)
proteins and of N-linked oligosaccharide addition
to many proteins.
the site of synthesis of secretory (exported)
proteins and of N-linked oligosaccharide addition
to many proteins.
RER
Mucus-secreting goblet cells of
the small intestine and
antibody-secreting plasma
cells are rich in
RER.
what cells are particularly rich in RER.
Mucus-secreting goblet cells of
the small intestine and
antibody-secreting plasma
cells
SER is the site of
steroid synthesis and detoxification
of drugs and poisons.
the site of steroid synthesis and detoxification
of drugs and poisons.
SER
what cells are particularly rich in SER.
Liver hepatocytes and
steroid hormone–producing
cells of the adrenal cortex
Liver hepatocytes and
steroid hormone–producing
cells of the adrenal cortex
are rich in
SER.
6 Functions of Golgi
apparatus
1. Distribution center of proteins and lipids from
ER to the plasma membrane, lysosomes, and
secretory vesicles
2. Modifies N-oligosaccharides
3. Adds O-oligosaccharides
4. Addition of mannose-6-phosphate
5. Proteoglycan assembly
6. Sulfation
I-cell disease

mech
failure of addition of mannose-6-phosphate to
lysosome proteins, enzymes
are secreted outside the cell
instead of being targeted to
the lysosome.
failure of addition of mannose-6-phosphate to
lysosome proteins, enzymes
are secreted outside the cell
instead of being targeted to
the lysosome.
I-cell disease:
I-cell disease

clinical findings
Characterized by coarse facial
features, clouded corneas,
restricted joint movement,
and high plasma levels of
lysosomal enzymes. Often
fatal in childhood.
Characterized by coarse facial
features, clouded corneas,
restricted joint movement,
and high plasma levels of
lysosomal enzymes. Often
fatal in childhood.
I-cell disease

clinical findings
Vesicular trafficking proteins:

COP I
Retrograde,
Golgi → ER.
Vesicular trafficking proteins:

Retrograde,
Golgi → ER.
COP I
Vesicular trafficking proteins:

COP II
Anterograde,
RER → cis-Golgi.
Vesicular trafficking proteins:

Anterograde, RER → cis-Golgi.
COP II
Vesicular trafficking proteins:

Clathrin
trans-Golgi →
lysosomes, plasma
membrane → endosomes
(receptor-mediated
endocytosis).
Vesicular trafficking proteins:

trans-Golgi →
lysosomes, plasma
membrane → endosomes
(receptor-mediated
endocytosis).
Clathrin
Microtubule

structure
Cylindrical structure 24 nm in diameter and of variable
length. A helical array of polymerized dimers of α-
and β-tubulin (13 per circumference). Each dimer
has 2 GTP bound.
Microtubule

functions
has 2 GTP bound. Incorporated into flagella, cilia,
mitotic spindles.Microtubules are also involved in slow axoplasmic
transport in neurons.
Microtubule

speeds
Grows slowly, collapses quickly.
Drugs that act on microtubules:
1. Mebendazole/thiabendazole
(antihelminthic)
2. Taxol (anti–breast cancer)
3. Griseofulvin (antifungal)
4. Vincristine/vinblastine
(anti-cancer)
5. Colchicine (anti-gout)
is due to a microtubule
polymerization defect
resulting in ↓ phagocytosis.
Chédiak-Higashi syndrome
Chédiak-Higashi syndrome

mech
is due to a microtubule
polymerization defect
resulting in ↓ phagocytosis.
Cilia structure
9 + + 2 arrangement of microtubules.
Dynein is an ATPase that links peripheral
9 doublets and causes bending of cilium by
differential sliding of doublets.
9 + + 2 arrangement of microtubules.
Dynein is an ATPase that links peripheral 9 doublets and causes bending of cilium by differential sliding of doublets.
Cilia structure
Molecular motors
Dynein =
Kinesin =
Molecular motors
Dynein = retrograde.
Kinesin = anterograde.
Molecular motors
retrograde.
anterograde.
Molecular motors
Dynein = retrograde.
Kinesin = anterograde.
Kartagener’s syndrome

mech and clinical findings
Immotile cilia due to a dynein arm defect. Results in male and female infertility (sperm
immotile), bronchiectasis, and recurrent sinusitis (bacteria and particles not
pushed out); associated with situs inversus.
Plasma membrane composition with %'s
Asymmetric fluid bilayer.
Contains cholesterol (~50%), phospholipids (~50%), sphingolipids, glycolipids,
and proteins.
Plasma membrane wrt cholesterol
High cholesterol or long saturated fatty acid content → increased melting temperature.
Phosphatidylcholine
aka
lecithin
lecithin
aka
Phosphatidylcholine
Phosphatidylcholine
(lecithin) function
Major component of RBC membranes, of myelin, bile, and surfactant (DPPC–
dipalmitoyl PC).
Used in esterification of cholesterol (LCAT is lecithin-cholesterol acyltransferase).
Major component of RBC membranes, of myelin, bile, and surfactant
Phosphatidylcholine
(lecithin)
Na+-K+ATPase

location and orientation
Na+-K+ATPase is located in the plasma membrane
with ATP site on cytoplasmic side. For each ATP
consumed, 3 Na+ go out and 2 K+ come in.
Ouabain

mech
inhibits Na+-K+ATPase by binding to K+ site.
inhibits Na+-K+ATPase by binding to K+ site
Ouabain
Na+-K+ATPase

wrt cardiac glycosides
Cardiac glycosides (digoxin,
digitoxin) also inhibit the
Na+-K+ATPase, causing ↑
cardiac contractility.
2K+
Most abundant protein in the human body.
Collagen
Collagen

how common
Most abundant protein in the human body.
Collagen

general function
Organizes and strengthens extracellular matrix.
Organizes and strengthens extracellular matrix.
Collagen
Collagen Types

Type I
(90%)––Bone, Skin, Tendon, dentin, fascia, cornea, late wound repair.
Collagen Types

Bone, Skin, Tendon, dentin, fascia, cornea, late wound repair.
Type I
Collagen Types

Type II
Cartilage (including hyaline), vitreous body, nucleus pulposus.

Type II: carTWOlage.
Collagen Types

Cartilage (including hyaline), vitreous body, nucleus pulposus.
Type II

Type II: carTWOlage.
Collagen Types

Type III (Reticulin)
skin, blood vessels, uterus,
fetal tissue, granulation tissue.
Collagen Types

skin, blood vessels, uterus,
fetal tissue, granulation tissue.
Type III (Reticulin)
Collagen Types

Type IV
Basement membrane or basal lamina.

Type IV: Under the floor
(basement membrane)..
Collagen Types

Basement membrane or basal lamina.
Type IV

Type IV: Under the floor
(basement membrane).
Collagen

Type III aka
Reticulin
Reticulin aka
Type III Collagen
Collagen synthesis and structure

steps inside fibroblasts and where inside of them
1. Synthesis (RER)
2. Hydroxylation
(ER)
3. Glycosylation
(Golgi)
4. Exocytosis
Collagen synthesis and structure

steps outside fibroblasts
5. Proteolytic
processing
6. Cross-linking
Collagen synthesis and structure

Synthesis (RER)
Translation of collagen α chains (preprocollagen)—
usually Gly-X-Y polypeptide (X and Y are
proline, hydroxyproline, or hydroxylysine).
Collagen synthesis and structure

Translation of collagen α chains (preprocollagen)—
usually Gly-X-Y polypeptide (X and Y are
proline, hydroxyproline, or hydroxylysine).
1. Synthesis (RER)
Collagen synthesis and structure

Hydroxylation of specific proline and lysine
residues (requires vitamin C).
2. Hydroxylation
(ER)
Collagen synthesis and structure

Hydroxylation
(ER)
Hydroxylation of specific proline and lysine
residues (requires vitamin C).
Collagen synthesis and structure

Glycosylation of pro-α-chain lysine residues and
formation of procollagen (triple helix of three
collagen α chains).
Glycosylation
(Golgi)
Collagen synthesis and structure

Glycosylation
(Golgi)
Glycosylation of pro-α-chain lysine residues and
formation of procollagen (triple helix of three
collagen α chains).
Collagen synthesis and structure

Exocytosis of procollagen into extracellular
space.
4. Exocytosis
Collagen synthesis and structure

4. Exocytosis
Exocytosis of procollagen into extracellular
space.
Collagen synthesis and structure

5. Proteolytic
processing
Cleavage of terminal regions of procollagen
transforms it into insoluble tropocollagen.
Collagen synthesis and structure

Cleavage of terminal regions of procollagen
transforms it into insoluble tropocollagen.
5. Proteolytic
processing
Collagen synthesis and structure

6. Cross-linking
Reinforcement of many staggered tropocollagen
molecules by covalent lysine-hydroxylysine cross-linkage (by lysyl oxidase) to make col-
lagen fibrils.
Collagen synthesis and structure

Reinforcement of many staggered tropocollagen
molecules by covalent lysine-hydroxylysine cross-linkage (by lysyl oxidase) to make col-
lagen fibrils.
6. Cross-linking
Ehlers-Danlos syndrome

mech and clinical findings
Faulty collagen synthesis (Type III is most frequently
affected (resulting in blood
vessel instability) causing:
1. Hyperextensible skin
2. Tendency to bleed (easy bruising)
3. Hypermobile joints
4.Associated with berry aneurysms.
Osteogenesis imperfecta

4 findings
1. Multiple fractures
2. Blue sclerae
3. Hearing loss (abnormal middle ear bones)
4. Dental imperfections due to lack of dentition
Osteogenesis imperfecta

worst type and findings
Type II is fatal in utero or in
the neonatal period.
5 Immunohistochemical stains
and associated cell types
Vimentin - Connective tissue

Desmin - Muscle

Cytokeratin - Epithelial cells

Glial fibrillary acid proteins (GFAP) - Neuroglia

Neurofilaments - Neurons
Stretchy protein within lungs, large arteries, elastic
ligaments.
Elastin
Elastin

what and where
Stretchy protein within lungs, large arteries, elastic
ligaments.
Elastin

structure
Rich in proline and lysine, nonhydroxylated forms.
Elastin

wrt diseases
Emphysema can be caused by
excess elastase activity.
????? inhibits elastase.
α1-antitrypsin
α1-antitrypsin inhibits ??????
elastase.
Marfan’s syndrome is caused
by a defect in?
fibrillin.
Metabolism sites

Mitochondria only
Fatty acid oxidation (β-oxidation), acetyl-CoA production, Krebs cycle.
Metabolism sites

Cytoplasm only
Glycolysis, fatty acid synthesis, HMP shunt, protein synthesis (RER), steroid synthesis
(SER).
Metabolism sites

Both Mitochondria and Cytoplasm
heme synthesis, urea cycle, Gluconeogenesis,

"HUGs take 2"
Aerobic metabolism of glucose produces ???? via malate shuttle,
38 ATP
Aerobic metabolism of glucose produces ???? via G3P shuttle.
36
Aerobic metabolism of glucose produces 38 ATP via
malate shuttle
Aerobic metabolism of glucose produces 36 ATP via
G3P shuttle.
Anaerobic glycolysis produces ???? per glucose molecule.
only 2 net ATP
Activated carriers (what carries/what is carried by)

ATP
Phosphoryl
Activated carriers (what carries/what is carried by)

Phosphoryl
(ATP).
Activated carriers (what carries/what is carried by)

Electrons
(NADH, NADPH, FADH2).
Activated carriers (what carries/what is carried by)

NADH, NADPH, FADH2
Electrons
Activated carriers (what carries/what is carried by)

Acyl
(coenzyme A, lipoamide).
Activated carriers (what carries/what is carried by)

coenzyme A
Acyl
Activated carriers (what carries/what is carried by)

lipoamide
Acyl
Activated carriers (what carries/what is carried by)

CO2
biotin
Activated carriers (what carries/what is carried by)

biotin
CO2
Activated carriers (what carries/what is carried by)

1-carbon units
(tetrahydrofolates).
Activated carriers (what carries/what is carried by)

tetrahydrofolates
1-carbon units
Activated carriers (what carries/what is carried by)

CH3 groups
(SAM).
Activated carriers (what carries/what is carried by)

SAM
CH3 groups
Activated carriers (what carries/what is carried by)

TPP
Aldehydes
Activated carriers (what carries/what is carried by)

Aldehydes
(TPP).
Rate-determining enzymes of metabolic processes (process/enzyme)

De novo pyrimidine
synthesis
Aspartate transcarbamylase (ATCase)
Rate-determining enzymes of metabolic processes (process/enzyme)

Aspartate transcarbamylase (ATCase)
De novo pyrimidine
synthesis
Rate-determining enzymes of metabolic processes (process/enzyme)

De novo purine
svnthesis
Glutamine-PRPP amidotransferase
Rate-determining enzymes of metabolic processes (process/enzyme)

Glutamine-PRPP amidotransferase
De novo purine
svnthesis
Rate-determining enzymes of metabolic processes (process/enzyme)

Glycolysis
PFK-1
Rate-determining enzymes of metabolic processes (process/enzyme)

PFK-1
Glycolysis
Rate-determining enzymes of metabolic processes (process/enzyme)

F 1,6-bisphosphotase (FBP-1)
Gluconeogenesis
Rate-determining enzymes of metabolic processes (process/enzyme)

Gluconeogenesis
F 1,6-bisphosphotase (FBP-1)
Rate-determining enzymes of metabolic processes (process/enzyme)

TCA cycle
lsocitrate dehydrogenase
Rate-determining enzymes of metabolic processes (process/enzyme)

lsocitrate dehydrogenase
TCA cycle
Rate-determining enzymes of metabolic processes (process/enzyme)

Glycogen synthesis
Glycogen synthase
Rate-determining enzymes of metabolic processes (process/enzyme)

Glycogen synthase
Glycogen synthesis
Rate-determining enzymes of metabolic processes (process/enzyme)

Glycogenolysis
Glycogen phosphorylase
Rate-determining enzymes of metabolic processes (process/enzyme)

Glycogen phosphorylase
Glycogenolysis
Rate-determining enzymes of metabolic processes (process/enzyme)

HMP shunt
Glucose-6-phosphate dehydrogenase (G6PD)
Rate-determining enzymes of metabolic processes (process/enzyme)

Glucose-6-phosphate dehydrogenase (G6PD)
HMP shunt
Rate-determining enzymes of metabolic processes (process/enzyme)

Fatty acid synthesis
Acetyl-CoA carboxylase (ACC)
Rate-determining enzymes of metabolic processes (process/enzyme)

Acetyl-CoA carboxylase (ACC)
Fatty acid synthesis
Rate-determining enzymes of metabolic processes (process/enzyme)

Fatty acid oxidation
Carnitine a~~ltransferase I
Rate-determining enzymes of metabolic processes (process/enzyme)

Carnitine a~~ltransferase I
Fatty acid oxidation
Rate-determining enzymes of metabolic processes (process/enzyme)

Ketogenesis
HMG-CoA synthase
Rate-determining enzymes of metabolic processes (process/enzyme)

HMG-CoA synthase
Ketogenesis
Rate-determining enzymes of metabolic processes (process/enzyme)

HMG-CoA reductase
Cholesterol synthesis
Rate-determining enzymes of metabolic processes (process/enzyme)

Cholesterol synthesis
HMG-CoA reductase
Rate-determining enzymes of metabolic processes (process/enzyme)

Heme synthesis
ALA synthase
Rate-determining enzymes of metabolic processes (process/enzyme)

ALA synthase
Heme synthesis
Rate-determining enzymes of metabolic processes (process/enzyme)

Carbamoyl phosphate synthase I
Urea cycle
Rate-determining enzymes of metabolic processes (process/enzyme)

Urea cycle
Carbamoyl phosphate synthase I
ATP + methionine →
S-adenosyl-
methionine (SAM)
SAM

function/regeneration
SAM the methyl donor man.

SAM transfers methyl units. Regeneration of methionine (and thus SAM) is
dependent on vitamin B12.
Universal electron
acceptors
Nicotinamides (NAD+, NADP+) and flavin
nucleotides (FAD+).
NADPH is a product of
the HMP shunt.
NAD+ is generally used in
catabolic processes to
carry reducing equivalents away as NADH.
NADPH is generally used in
anabolic processes (steroid
and fatty acid synthesis) as a supply of reducing
equivalents.
NADPH is used in:
1. Anabolic processes
2. Respiratory burst
3. P-450
?????is used in:

1. Anabolic processes
2. Respiratory burst
3. P-450
NADPH
Hexokinase

WRT
locations, affinity, capacity, inhibition
(ubiquitous)
High affinity,
low capacity.
Feedback inhibited by glucose-6- phosphate.
Glucokinase

WRT
locations, affinity, capacity, inhibition
(liver)
Low affinity,
high capacity.
No feedback inhibition.
Glucokinase

role
Phosphorylates excess glucose
(e.g., after a meal) to sequester
it in the liver.
Phosphorylates excess glucose
(e.g., after a meal) to sequester
it in the liver.
Glucokinase
the most potent activator of
phosphofructokinase (how strong)
F2,6BP

(overrides inhibition by ATP
and citrate).
Glycolytic enzyme deficiency

%'s
Pyruvate kinase (95%), glucose phosphate (4%),
Glycolytic enzyme deficiency

clinical findings (why)
Associated with hemolytic anemia.

RBCs metabolize glucose
anaerobically (no
mitochondria) and thus
depend solely on glycolysis.
Pyruvate dehydrogenase complex

cofactors
1. Pyrophosphate (B1, thiamine; TPP)
2. FAD (B2, riboflavin)
3. NAD (B3, niacin)
4. CoA (B5, pantothenate)
5. Lipoic acid
Pyruvate dehydrogenase complex

is similar to
α-ketoglutarate
dehydrogenase complex
(same cofactors, similar
substrate and action).
α-ketoglutarate dehydrogenase complex

is similar to
Pyruvate dehydrogenase complex
(same cofactors, similar
substrate and action).
Arsenic

mech and clinical findings
Arsenic inhibits lipoic acid (Pyruvate dehydrogenase complex cofactor):

Vomiting, Rice water stools
Garlic breath
Vomiting, Rice water stools
Garlic breath
Arsenic
Pyruvate dehydrogenase complex

reaction
Reaction: pyruvate + NAD+ + CoA → acetyl-CoA + CO2 + NADH.
Pyruvate dehydrogenase complex

activated by
Activated by exercise:
↑ NAD+/NADH ratio
↑ ADP
↑ Ca2+
the only purely ketogenic amino
acids.
Lysine and Leucine––
Pyruvate dehydrogenase deficiency

mech
Causes backup of substrate (pyruvate and alanine),
resulting in lactic acidosis. Can be congenital or
acquired (as in alcoholics due to B1 deficiency).
Pyruvate dehydrogenase deficiency

findings
neurologic defects.
Pyruvate dehydrogenase deficiency


Tx
↑ intake of ketogenic nutrients (e.g., high fat content or ↑ lysine and leucine).
# are needed to generate glucose from pyruvate.
6 ATP equivalents
Pyruvate metabolism

Alanine
carries amino groups
to the liver from muscle.
Pyruvate metabolism

Oxaloacetate
can replenish
TCA cycle or be used in
gluconeogenesis.
Cori cycle

mech and why
Transfers excess reducing
equivalents from RBCs and
muscle to liver, allowing
muscle to function
anaerobically (net 2 ATP).
Shifts metabolic burden to the
liver.
Transfers excess reducing
equivalents from RBCs and
muscle to liver, allowing
muscle to function
anaerobically (net 2 ATP).
Shifts metabolic burden to the
liver.
Cori cycle
TCA cycle

what is produced/per what
Produces 3 NADH, 1 FADH2,
2 CO2, 1 GTP per acetyl-
CoA = 12 ATP/acetyl-CoA
(2× everything per glucose)
TCA cycle

complex and features
α-ketoglutarate dehydrogenase
complex requires same
cofactors as the pyruvate
dehydrogenase complex (B1,
B2, B3, B5, lipoic acid).
TCA cycle

order of things from Acetyl-CoA
Can IKeep Selling Sex
For Money, Officer?

Citrate
Isocitrate
α-ketoglutarate
Succinyl-CoA
Succinate
Fumarate
Malate
Oxalo-acetate
Electron transport
chain

yields from input's
1 NADH → 3 ATP;

1 FADH2 → 2 ATP.
Oxidative phosphorylation poisons

↑ permeability of membrane, causing a ↓ proton
gradient and ↑ O2 consumption. ATP synthesis stops, but electron transport continues.
Uncoupling agents

(UCP, 2,4-DNP, aspirin)
Oxidative phosphorylation poisons

UCP, 2,4-DNP, aspirin
Uncoupling agents

↑ permeability of membrane, causing a ↓ proton
gradient and ↑ O2 consumption. ATP synthesis stops, but electron transport continues.
Oxidative phosphorylation poisons

Rotenone, CN–, antimycin A,
CO
Electron transport
inhibitors
Oxidative phosphorylation poisons

Directly inhibit electron transport, causing a ↓
proton gradient and block of ATP synthesis.
Electron transport
inhibitors
-Rotenone,
-cyanide,
-antimycin A,
-CO
Oxidative phosphorylation poisons

Directly inhibit mitochondrial ATPase, causing
an ↑ proton gradient, but no ATP is produced
because electron transport stops.
ATPase inhibitors

Oligomycin
Oxidative phosphorylation poisons

Oligomycin
ATPase inhibitors

Directly inhibit mitochondrial ATPase, causing
an ↑ proton gradient, but no ATP is produced
because electron transport stops.
Gluconeogenesis, irreversible enzymes (where, what, regulation/requirements)

Pyruvate carboxylase
In mitochondria.
Pyruvate → oxaloacetate.

Requires biotin, ATP.
Activated by acetyl-CoA.
Gluconeogenesis, irreversible enzymes

In mitochondria.
Pyruvate → oxaloacetate.

Requires biotin, ATP.
Activated by acetyl-CoA.
Pyruvate carboxylase
Gluconeogenesis, irreversible enzymes (where, what, requirements)

PEP carboxykinase
In cytosol.
Oxaloacetate → phosphoenolpyruvate.

Requires GTP.
Gluconeogenesis, irreversible enzymes

In cytosol.
Oxaloacetate → phosphoenolpyruvate.

Requires GTP.
PEP carboxykinase
Gluconeogenesis, irreversible enzymes (where, what, regulation/requirements)

Fructose-1,6-
bisphosphatase
In cytosol.

Fructose-1,6-bisphosphate →
fructose-6-P.
Gluconeogenesis, irreversible enzymes

In cytosol.

Fructose-1,6-bisphosphate →
fructose-6-P.
Fructose-1,6-
bisphosphatase
Gluconeogenesis, irreversible enzymes (where, what, regulation/requirements)

Glucose-6-
phosphatase
In ER. Glucose-6-P → glucose.
Gluconeogenesis, irreversible enzymes

name them
Pathway Produces Fresh Glucose.

-Pyruvate carboxylase
-PEP carboxykinase
-Fructose-1,6-bisphosphatase
-Glucose-6- phosphatase
Gluconeogenesis, irreversible enzymes

In ER. Glucose-6-P → glucose.
Glucose-6-
phosphatase
Gluconeogenesis, irreversible enzymes

locations in body
Above enzymes found only in liver, kidney, intestinal epithelium. Muscle cannot
participate in gluconeogenesis.
Deficiency of the key gluconeogenic enzymes causes
hypoglycemia.
Pentose phosphate pathway (HMP
shunt)

why
Produces NADPH, which is required for fatty acid and steroid biosynthesis and for
glutathione reduction inside RBCs. and nucleotide synthesis
Pentose phosphate pathway (HMP
shunt)

where (in the the cell and body
All reactions of this pathway occur in the cytoplasm.
Sites: lactating mammary glands, liver, adrenal cortex––all sites of fatty acid or steroid
synthesis.
Pentose phosphate pathway (HMP
shunt)

wrt ATP
No ATP is used or produced.
Pentose phosphate pathway
aka
HMP shunt
HMP shunt aka
Pentose phosphate pathway
Pentose phosphate pathway (HMP
shunt)

Oxidative reaction features, key enzymes, and products (with reasons)
(irreversible)

Glucose-6-phosphate dehydrogenase

NADPH
Pentose phosphate pathway (HMP
shunt)

Nonoxidative reaction features, key enzymes, and products (with reasons)
(reversible)

Transketolases (require thiamine)

Ribose-5-phosphate (Ribose-5-phosphate (for
nucleotide synthesis), G3P,
F6P (glycolytic intermediates)
Glucose-6-phosphate
dehydrogenase
deficiency

who
G6PD deficiency is more
prevalent among blacks.
Glucose-6-phosphate
dehydrogenase
deficiency

histo
Heinz bodies––altered
Hemoglobin precipitates
within RBCs.
Glucose-6-phosphate
dehydrogenase
deficiency

clinical findings
hemolytic anemia due to poor
RBC defense against oxidizing agents (fava beans, sulfonamides, primaquine) and antituberculosis drugs.
hemolytic anemia due to poor
RBC defense against oxidizing agents (fava beans, sulfonamides, primaquine) and antituberculosis drugs.
Glucose-6-phosphate
dehydrogenase
deficiency
Fructose intolerance

mech
deficiency of aldolase B (recessive). fructose-1-phosphate accumulates, causing a ↓ in available phosphate, which results in inhibition of glycogenolysis
and gluconeogenesis.
Fructose intolerance

findings
hypoglycemia, jaundice, cirrhosis, vomiting.
Fructose intolerance

Tx
must ↓ intake of both fructose and sucrose (glucose + fructose).
Essential fructosuria
Involves a defect in fructokinase and is a benign, asymptomatic condition.
Symptoms: fructose appears in blood and urine.
Involves a defect in fructokinase and is a benign, asymptomatic condition.
fructose appears in blood and urine.
Essential fructosuria
Galactosemia

mech
Absence of galactose-1-phosphate uridyltransferase. Autosomal recessive. Damage is
caused by accumulation of toxic substances (including galactitol) rather than absence
of an essential compound.
Galactosemia

clinical findings
cataracts, hepatosplenomegaly, mental retardation.
Galactosemia

Tx
exclude galactose and lactose (galactose + glucose) from diet.
Amino acids

Ketogenic:
Leu, Lys
Amino acids

Glucogenic/ketogenic
Ile, Phe, Trp
Amino acids

Glucogenic
Met, Thr, Val, Arg, His
Amino acids

Essential
PVT. TIM HALL always argues, never tires":
Phe- Val- Thr- Trp- Ile- Met- His- Arg- Lue- Lys
Amino acids

Acidic
Asp and Glu
Amino acids

Basic (and relative strengths)
Arg, Lys, and His.
Arg is most basic.
His has no charge at body pH.
Hyperammonemia

who
Can be acquired (e.g., liver disease) or hereditary
(e.g., ornithine transcarbamoylase deficiency).
Hyperammonemia

mech
Excess NH4 depletes α-ketoglutarate, leading to
inhibition of TCA cycle.
Hyperammonemia

Tx
arginine.
Hyperammonemia

clinical findings
Ammonia intoxication: tremor,
slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision.
Urea cycle

what and why
Degrades amino acids into amino groups. Accounts
for 90% of nitrogen in urine.
Urea cycle

order
Ordinarily, Careless Crappers
Are Also Frivolous About
Urination.

Ornithine + Carbamoyl phosphate go to Citruline which combines with Aspartate going to Argininosuccinate releasing fumarate and arginine (which combines with water to release Urea and ornithine) back to top
Amino acid derivatives

Phenylalanine
from first to last

Tyrosine ^(Thyroxine)
to
Dopamine
to
Dopa ^(Melanin)
to
NE
to
Epi
Amino acid derivatives

Tryptophan
-Niacin ^ (NAD+/NADP+)
or
-Melatonin
or
-Serotonin
Amino acid derivatives

Histidine
Histamine
Amino acid derivatives

Glycine
to Porphyrin to Heme
Amino acid derivatives

Arginine
Urea
or
Nitric oxide
or
Creatine
Amino acid derivatives

Glutamate
GABA (glutamate decarboxylase—requires B6)
What is the original amino acid for

NE
Thyroxine
Tyrosine Dopamine Dopa Epi
Melanin
Phenylalanine
What is the original amino acid for

Niacin NAD+/NADP+
Melatonin
Serotonin
Tryptophan
What is the original amino acid for

Histamine
Histidine
What is the original amino acid for
Porphyrin Heme
Glycine
What is the original amino acid for

Urea
Nitric oxide
Creatine
Arginine
What is the original amino acid for

GABA (glutamate decarboxylase—requires B6)
Glutamate
Normally, phenylalanine is converted into
tyrosine
Phenylketones

name the three
––phenylacetate,
phenyllactate, and
phenylpyruvate.
Phenylketonuria

mech
there is ↓ phenylalanine
hydroxylase or ↓ tetrahydrobiopterin cofactor.
Tyrosine becomes essential and phenylalanine builds up, leading to excess phenylketones in urine.
Phenylketonuria

clinical findings
mental retardation, growth retardation, fair skin, eczema, musty body odor.
Phenylketonuria

Tx
Treatment: ↓ ↓ phenylalanine (contained in
aspartame, e.g., NutraSweet) and ↑ ↑ tyrosine in diet.
Alkaptonuria
aka
ochronosis
ochronosis
aka
Alkaptonuria
Alkaptonuria
(ochronosis)

mech and findings
Congenital deficiency of homogentisic acid oxidase in the degradative pathway of
tyrosine. Resulting alkapton bodies cause urine to turn black on standing. Also, the
connective tissue is dark. Benign disease. May have debilitating arthralgias.
Albinism

causes
Congenital deficiency of either of the following:
1. Tyrosinase (inability to synthesize melanin
from tyrosine)
2. Defective tyrosine transporters (↓ amounts of
tyrosine and thus melanin)

-Can result from a lack of migration of neural
crest cells.
Albinism

wrt inheritance
AR - Variable inheritance due to
locus heterogeneity.
Albinism

wrt risk
Lack of melanin results in an
↑ risk of skin cancer.
Homocystinuria
3 forms mech and Tx
1. Cystathionine synthase deficiency (treatment:
↓ Met and ↑ Cys in diet)
2. ↓ affinity of cystathionine synthase for
pyridoxal phosphate (treatment: ↑↑ vitamin
B6 in diet)
3. Methionine synthase deficiency
Homocystinuria
general mech
Results in excess homocysteine
in the urine. Cysteine
becomes essential.
Homocystinuria

findings
Can cause mental retardation,
osteoporosis, tall stature,
kyphosis, lens subluxation
(downward and inward), and
atherosclerosis (stroke and
MI).
Cystinuria

mech
Common (1:7000) inherited defect of renal tubular
amino acid transporter for Cystine, Ornithine,
Lysine, and Arginine in kidneys.

COLA
Cystinuria clinical findings and Tx
Excess cystine in urine can lead to the precipitation
of cystine kidney stones.

Treat with acetazolamide to
alkalinize the urine.
Maple syrup urine disease

mech
Blocked degradation of branched amino acids
(Ile, Val, Leu) "I Love Vermont maple syrup" due to ↓α-ketoacid dehydrogenase.
Causes ↑α-ketoacids in the blood, especially Leu.
Maple syrup urine disease

clinical findings
Urine smells like maple syrup.

Causes severe CNS defects, mental retardation, and
death.
Lesch-Nyhan syndrome

mech
Purine salvage problem owing to absence of HGPRTase. Results in excess uric acid production.
Lesch-Nyhan syndrome

findings
Findings: retardation, self-mutilation, aggression,
hyperuricemia, gout, and choreoathetosis.
retardation, self-mutilation, aggression, hyperuricemia, gout, and choreoathetosis.
Lesch-Nyhan syndrome
Adenosine deaminase deficiency

mech
Excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase. This prevents DNA synthesis and thus ↓ lymphocyte count.
1st disease to be treated by experimental
human gene therapy.
Adenosine deaminase deficiency
Adenosine deaminase deficiency

complications
SCID––severe combined
(T and B) immunodeficiency
Liver: fed state vs.
fasting state

what is released in fed state
just VLDL
Liver: fed state vs.
fasting state

what is released in fasting state
Glucose
and
Ketone
bodies
Liver: fed state vs.
fasting state

mnemonic
In the PHasting state,
PHosphorylate.
what cells don't need insulin to uptake glucose
BRICK L:
Brain
RBCs
Intestine
Cornea
Kidney
Liver
Where are different GLUT's
and different activities
-GLUT1: RBCs, brain
-GLUT2 (bidirectional): β islet cells, liver, kidney
-GLUT4 (insulin responsive):
adipose tissue, skeletal
muscle
5 Anabolic effects of insulin:
1. ↑ glucose transport
2. ↑ glycogen synthesis and storage
3. ↑ triglyceride synthesis and storage
4. ↑ Na retention (kidneys)
5. ↑ protein synthesis (muscles)
Serum C-peptide is not present with
exogenous insulin intake.
???? inhibits glucagon
release by α cells of pancreas.
insulin
Glycogen synthase

regulation in liver and muscle
Liver:
⊕Insulin and/or Glucose
-Glucagon and or Epinephrine

Muscle:
⊕Insulin
-Epinephrine
Glycogen phosphorylase

regulation in liver and muscle
Liver
⊕Epinephrine and or Glucagon
-Insulin

Muscle:
⊕AMP and/or epinephrine
-ATP and/or Insulin
Required for adipose
and skeletal muscle uptake of glucose.
Insulin
Glycogen storage diseases

names of the main ones
"Very Poor Carbohydrate
Metabolism"

Von Gierke’s disease (Type I)

Pompe’s disease(Type II)

Cori’s disease(Type III)

McArdle’s disease (Type V)
Glycogen storage diseases

#'s and features
12 types, all resulting in abnormal glycogen metabolism and an accumulation of glycogen within cells.
Von Gierke’s disease

Findings, Deficient enzyme and comments
Severe fasting hypoglycemia, ↑↑ glycogen in liver, ↑ blood
lactate, hepatomegaly.

Glucose-6-phosphate.

-The liver becomes a muscle. (Think about it.)
Pompe’s disease

Findings, Deficient enzyme and comments
Cardiomegaly and systemic
findings leading to early death.

Lysosomal α-1,4- glucosidase (acid maltase).

Pompe’s trashes the Pump (heart, liver, and muscle).
Cori’s disease

Findings, Deficient enzyme and comments
Milder form of Type I with normal
blood lactate levels.

Debranching enzyme
α-1,6-glucosidase.
McArdle’s disease

Findings, Deficient enzyme and comments
↑glycogen in muscle, but cannot break it down, leading to painful muscle cramps, myoglobinuria with strenuous exercise.

Skeletal muscle glycogen
phosphorylase.
↑glycogen in muscle, but cannot break it down, leading to painful muscle cramps, myoglobinuria with strenuous exercise.
McArdle’s disease
Severe fasting hypoglycemia, ↑↑
glycogen in liver, ↑ blood
lactate, hepatomegaly.
Von Gierke’s disease
Cardiomegaly and systemic
findings leading to early death.
Pompe’s disease
Inheritance of Lysosomal storage diseases
Fabry’s disease and Hunter’s syndrome are XR

the rest are AR
Fabry’s disease

Findings
/Deficient enzyme
/Accumulated substrate
Peripheral neuropathy of
hands/feet, angiokeratomas,
cardiovascular/renal disease

α-galactosidase A

Ceramide
trihexoside
Gaucher’s disease

Findings
/Deficient enzyme
/Accumulated substrate
Hepatosplenomegaly,
aseptic necrosis of femur,
bone crises, Gaucher’s cells
(macrophages)

β-glucocerebrosidase

Glucocerebroside
Niemann-Pick
disease

Findings
/Deficient enzyme
/Accumulated substrate
"No man picks (Niemann-Pick)
his nose with his sphinger
(sphingomyelinase)."

Progressive neurodegeneration,
hepatosplenomegaly, cherry-
red spot (on macula)

Sphingomyelinase

Sphingomyelin
Tay-Sachs disease

Findings
/Deficient enzyme
/Accumulated substrate
Progressive neurodegeneration,
developmental delay,
cherry-red spot, lysozymes
with onion skin

' Tay-SaX (Tay-Sachs)
lacks heXosaminidase." Hexosaminidase A

GM2 ganglioside
Krabbe’s disease

Findings
/Deficient enzyme
/Accumulated substrate
Peripheral neuropathy,
developmental delay,
optic atrophy

β-galactosidase

Galactocerebroside
Metachromatic
leukodystrophy

Findings
/Deficient enzyme
/Accumulated substrate
Central and peripheral
demyelination with ataxia,
dementia

Arylsulfatase A

Cerebroside sulfate
Hurler’s syndrome

Findings
/Deficient enzyme
/Accumulated substrate
Developmental delay,
gargoylism, airway obstruction, corneal clouding,
hepatosplenomegaly

α-L-iduronidase

Heparan sulfate,
dermatan sulfate
Hunter’s syndrome

Findings
/Deficient enzyme
/Accumulated substrate
Mild Hurler’s + aggressive
behavior, no corneal
clouding

Iduronate sulfatase


Heparan sulfate,
dermatan sulfate
Lysosomal storage diseases

names and general classes
Sphingoliposes:
Fabry’s disease - Gaucher’s disease - Niemann-Pick -
Tay-Sachs disease - Krabbe’s disease - Metachromatic
leukodystrophy

Mucopolysaccharidoses:
Hurler’s syndrome -Hunter’s syndrome
Lysosomal storage diseases

most common
Gaucher’s disease
Hepatosplenomegaly,
aseptic necrosis of femur,
bone crises, Gaucher’s cells
(macrophages)
Gaucher’s disease
Progressive neurodegeneration,
hepatosplenomegaly, cherry-
red spot (on macula)
Niemann-Pick
disease

Tay-Sachs disease
Peripheral neuropathy of
hands/feet, angiokeratomas,
cardiovascular/renal disease
Fabry’s disease
inability to utilize LCFAs
and toxic accumulation.
Carnitine deficiency:
Ketone bodies

where/how/why produced
In liver: fatty acid and amino acids → HMG-CoA → acetoacetate + β-hydroxybutyrate (to be used in muscle and brain Ketone bodies are metabolized by the brain to 2 molecules of
acetyl-CoA.)
Ketone bodies

when
prolonged starvation and diabetic ketoacidosis
Cholesterol synthesis

rate limiting step and mech
and wrt esterificatoin
Rate-limiting step is catalyzed by HMG-CoA
reductase, which converts HMG-CoA to mevalonate.
2⁄3 of plasma cholesterol is esterified
by lecithin-cholesterol acyltransferase (LCAT).
Lovastatin inhibits
HMG-
CoA reductase.
what inhibits HMG-
CoA reductase.
statins
Essential fatty acids

and why
Linoeic and linolenic acids.
Arachidonic acid, if linoleic acid is absent.

Eicosanoids are dependent on
essential fatty acids.
Lipases (function/which one)

degradation of dietary TG in small intestine.
Pancreatic lipase
Lipases (function/which one)

Pancreatic lipase
degradation of dietary TG in small intestine.
Lipases (function/which one)

Lipoprotein lipase
degradation of TG circulating in chylomicrons and VLDLs.
Lipases (function/which one)

degradation of TG circulating in chylomicrons and VLDLs.
Lipoprotein lipase
Lipases (function/which one)

Hepatic TG lipase
degradation of TG remaining in IDL.
Lipases (function/which one)

degradation of TG remaining in IDL.
Hepatic TG lipase
Lipases (function/which one)

Hormone-sensitive lipase
degradation of TG stored in adipocytes.
Lipases (function/which one)

degradation of TG stored in adipocytes.
Hormone-sensitive lipase
fat enzymes (function/which one)

Lecithin-cholesterol acyltransferase (LCAT)
catalyzes esterification of cholesterol.
fat enzymes (function/which one)

catalyzes esterification of cholesterol.
Lecithin-cholesterol acyltransferase (LCAT)
fat enzymes (function/which one)

Cholesterol ester transfer protein (CETP)
mediates transfer of cholesterol esters to other lipoprotein particles.
fat enzymes (function/which one)

mediates transfer of cholesterol esters to other lipoprotein particles.
Cholesterol ester transfer protein (CETP)
Major apolipoproteins

function of A-I
Activates LCAT.
Major apolipoproteins

Activates LCAT.
A-I
Major apolipoproteins

function of B-100
Binds to LDL receptor, mediates VLDL secretion.
Major apolipoproteins

Binds to LDL receptor, mediates VLDL secretion.
B-100
Major apolipoproteins

function of C-II
Cofactor for lipoprotein lipase.
Major apolipoproteins

Cofactor for lipoprotein lipase.
C-II
Major apolipoproteins

function of B-48
Mediates chylomicron secretion.
Major apolipoproteins

Mediates chylomicron secretion.
B-48
Major apolipoproteins

Mediates Extra (remnant) uptake.
E
Major apolipoproteins

function of E
Mediates Extra (remnant) uptake.
Which lipoproteins are on

IDL
B-100

E
Which lipoproteins are on

LDL
B-100
Which lipoproteins are on

VLDL
C-II
B-100
E
Which lipoproteins are on

Chylomicron remnant
B-48
E
Which lipoproteins are on

Chylomicron
A
B-48
C-II
E
Lipoprotein

compositions
Lipoproteins are composed of varying proportions of cholesterol, triglycerides,
and phospholipids.
carry most cholestero
LDL and HDL
Function and route

Chylomicron
Delivers dietary triglycerides to peripheral tissues and
dietary cholesterol to liver. Secreted by intestinal
epithelial cells.
Function and route

VLDL
Delivers hepatic triglycerides to peripheral tissues
Secreted by liver.
Function and route

IDL
Formed in the degradation of VLDL. Delivers triglycerides and cholesterol to liver, where they
are degraded to LDL.
Function and route

LDL
Delivers hepatic cholesterol to peripheral tissues.
Formed by lipoprotein lipase modification of
VLDL in the peripheral tissue. Taken up by targe
cells via receptor-mediated endocytosis.
Function and route

HDL
Mediates centripetal transport of cholesterol (reverse cholesterol transport, from periphery to liver). Acts as a repository for apoC and apoE (which are
needed for chylomicron and VLDL metabolism).
Secreted from both liver and intestine.
Familial dyslipidemias

Type I

-aka
-What is increased
-elevated blood levels
-pathophys
I––hyperchylomicronemia

Chylomicrons

TG, cholesterol

Lipoprotein lipase deficiency
or altered apolipoprotein C-II
Familial dyslipidemias


Type IIa

-aka
-What is increased
-elevated blood levels
-pathophys
IIa––hypercholesterolemia

LDL

Cholesterol

↓ LDL receptors
Familial dyslipidemias


Type IV

-aka
-What is increased
-elevated blood levels
-pathophys
IV––hypertriglyceridemia

VLDL

TG

Hepatic overproduction of VLDL
Underproduction of heme causes ?

Accumulation of
intermediates causes ?
microcytic hypochromic anemia.

porphyrias.
Porphyrias

name them
Lead poisoning

Acute intermittent porphyria

Porphyria cutanea tarda
Porphyrias

symptyoms
Symptoms = 5 P’s:
Painful abdomen, Pink urine,
Polyneuropathy, Psychological
disturbances, Precipitated by drugs
Affected enzyme and
Accumulated substrate in urine

Lead poisoning
Ferrochelatase and ALA dehydrase

Coproporhyrin and ALA
Affected enzyme and
Accumulated substrate in urine

Acute intermittent porphyria
porphobilinogen deaminase

Porphobilinogen and δ-ALA
Affected enzyme and
Accumulated substrate in urine

Porphyria cutanea tarda
Uroporphyrinogen decarboxylase

Uroporphyrin (tea-colored)
Heme catabolism

scavanve mech
Heme is scavenged from RBCs and Fe2+ is reused. Heme →biliverdin →bilirubin
what makes bruises blue/green
biliverdin
Heme catabolism

wrt newborns
jaundiced newborns are put under UV light which converts bilirubin into urine- solubile products
Hemoglobin

formations and implications
1. T (taut) form has low affinity for O2.
2. R (relaxed) form has high affinity for O2
(300×).
Hemoglobin

wrt allosteric
Hemoglobin exhibits positive
cooperativity and negative allostery (accounts for the sigmoid-shaped O2
dissociation curve for hemoglobin),
unlike myoglobin.
how can fetal Hb take O2 from Hb
Fetal hemoglobin (2α and 2γ
subunits) has lower affinity
for 2,3-BPG than adult
hemoglobin (HbA) and thus
has higher affinity for O2.
↑ Cl−, H+, CO2, 2,3-BPG, and temperature shifts dissociation curve to right, leading to ↑ O2 unloading)

HOW?
favor T form over R form promoting O2 unloading (negative allosteric regulation).
CO2 transport in
blood by Hb (where)
CO2 (primarily as bicarbonate) binds to amino acids in globin chain at N terminus, but not
to heme.
cyanide poisoning

Tx and mech
Administer nitrites in cyanide
poisoning to oxidize hemoglobin to methemoglobin.
Methemoglobin
Oxidized form of hemoglobin (ferric, Fe3+) that does not bind O2 as readily, but has ↑ affinity for CN–.
Iron in hemoglobin is normally
in a reduced
state (ferrous, Fe2+).
Carboxyhemoglobin
Form of hemoglobin bound to CO in place of O2.
Form of hemoglobin bound to CO in place of O2.
Carboxyhemoglobin
Oxidized form of hemoglobin (ferric, Fe3+) that does not bind O2 as readily, but has ↑ affinity for CN–.
Methemoglobin
Methemoglobin

Tx
Treat toxic levels of
METHemoglobin with
METHylene blue.
CO has a ?????? affinity
than O2 for hemoglobin.
200× greater
Polymerase chain
reaction (PCR)

steps
1. DNA is denatured by heating to generate 2 separate strands
2. During cooling, excess premade DNA primers anneal to a specific sequence on eac
strand to be amplified
3. Heat-stable DNA polymerase replicates the DNA sequence following each primer
different direction blots
SNoW DRoP:
Southern = DNA
Northern = RNA
Western = Protein
A rapid immunologic technique testing for antigen-antibody reactivity.
Enzyme-linked immunosorbent assay (ELISA)
Enzyme-linked immunosorbentassay (ELISA)

why
to determinewhether a particular
antibody (e.g., anti-HIV) is
present in a patient’s blood
ample. Both the sensitivity
Fluorescence in situ hybridization (FISH)
Fluorescent probe binds to specific gene site of interest.
Specific localization of genes and direct visualization of anomalies at molecular level.
Genetic terms

Variable expression
Nature and severity of the phenotype varies from 1 individual to another.
Genetic terms

Nature and severity of the phenotype varies from 1 individual to another.
Variable expression
Genetic terms

Incomplete penetrance
Not all individuals with a mutant genotype show the mutant phenotype.
Genetic terms

Not all individuals with a mutant genotype show the mutant phenotype.
Incomplete penetrance
Genetic terms

Pleiotropy
1 gene has > 1 effect on an individual’s phenotype.
Genetic terms

1 gene has > 1 effect on an individual’s phenotype.
Pleiotropy
Genetic terms

Imprinting
Differences in phenotype depend on whether the mutation is of maternal or paternal
origin (e.g., AngelMan’s syndrome [Maternal], Prader-Willi syndrome [Paternal]).
Genetic terms

Differences in phenotype depend on whether the mutation is of maternal or paternal
origin
Imprinting
Genetic terms

Anticipation
Severity of disease worsens or age of onset of disease is earlier in succeeding generations
(e.g., Huntington’s disease).
Genetic terms

Severity of disease worsens or age of onset of disease is earlier in succeeding generations
Anticipation
Genetic terms

Loss of heterozygosity
If a patient inherits or develops a mutation in a tumor suppressor gene, the complementary
allele must be deleted/mutated before cancer develops. This is not true of oncogenes.
Genetic terms

If a patient inherits or develops a mutation in a tumor suppressor gene, the complementary
allele must be deleted/mutated before cancer develops. This is not true of oncogenes.
Loss of heterozygosity
Genetic terms

Dominant negative mutation
Exerts a dominant effect. A heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning.
Genetic terms

Exerts a dominant effect. A heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning.
Dominant negative mutation
Genetic terms

Linkage disequilibrium
Tendency for certain alleles at 2 linked loci to occur together more often than
expected by chance. Measured in a population, not in a family, and often varies in
different populations.
Genetic terms

Tendency for certain alleles at 2 linked loci to occur together more often than
expected by chance. Measured in a population, not in a family, and often varies in
different populations.
Linkage disequilibrium
Genetic terms

Mosaicism
Occurs when cells in the body have different genetic makeup (e.g., lyonization––
random X inactivation in females).
Genetic terms

Occurs when cells in the body have different genetic makeup
Mosaicism
Genetic terms

Locus heterogeneity
Mutations at different loci can produce the same phenotype (e.g., albinism).
Genetic terms

Mutations at different loci can produce the same phenotype
Locus heterogeneity
Hardy-Weinberg law assumes:
1. no mutation occurring at the locus
2. There is no selection for
any of the genotypes at the locus
3. random mating
4. no migration
being considered
Imprinting

describe the main example
Prader-Willi ( Deletion of normally active paternal allele)

Angelman’s syndrome (Deletion of normally active maternal allele)
Prader-Willi

findings
Mental retardation, obesity,
hypogonadism, hypotonia.
Angelman’s syndrome

findings
Mental retardation, seizures,
ataxia, inappropriate laughter
(happy puppet).
Mental retardation, seizures,
ataxia, inappropriate laughter
(happy puppet).
Angelman’s syndrome
Mental retardation, obesity,
hypogonadism, hypotonia.
Prader-Willi
Mitochondrial inheritance

diseases
Leber’s hereditary optic
neuropathy;

mitochondrial
myopathies.
Mitochondrial inheritance

mech
Transmitted only through mother. All offspring of
affected females may show signs of disease.
AR/AD/XR/XD

Adult polycystic kidney
disease
AD
AR/AD/XR/XD

Familial
hypercholesterolemia
AD
AR/AD/XR/XD

Marfan’s syndrome
AD
AR/AD/XR/XD

von Recklinghausen’s
disease
AD
AR/AD/XR/XD

Neurofibromatosis
type 1
AD
AR/AD/XR/XD

Neurofibromatosis
type 2
AD
AR/AD/XR/XD

Tuberous sclerosis
AD
AR/AD/XR/XD

Von Hippel–Lindau
disease
AD
AR/AD/XR/XD

Huntington’s disease
AD
AR/AD/XR/XD

Familial adenomatous
polyposis
AD
AR/AD/XR/XD

Hereditary
spherocytosis
AD
AR/AD/XR/XD

Achondroplasia
AD
AR/AD/XR/XD

Cystic fibrosis
AR
AR/AD/XR/XD

albinism
AR
AR/AD/XR/XD

α1-antitrypsin deficiency
AR
AR/AD/XR/XD

phenylketonuria
AR
AR/AD/XR/XD

thalassemias
AR
AR/AD/XR/XD

sickle cell anemias
AR
AR/AD/XR/XD

glycogen storage diseases
AR
AR/AD/XR/XD

mucopolysaccharidoses
AR
(except Hunter’s),
AR/AD/XR/XD

sphingolipidoses
AR
(except Fabry’s)
AR/AD/XR/XD

infant polycystic kidney disease
AR
AR/AD/XR/XD

hemochromatosis
AR
AR/AD/XR/XD

Bruton's agammaglobulinemia
XR

Be Wise, Fool's GOLD Heeds
False Hope.
AR/AD/XR/XD

Wiskott-Aldrich syndrome
XR

Be Wise, Fool's GOLD Heeds
False Hope.
AR/AD/XR/XD

Fragile X
XR

Be Wise, Fool's GOLD Heeds
False Hope.
AR/AD/XR/XD

G6PD deficiency
XR

Be Wise, Fool's GOLD Heeds
False Hope.
AR/AD/XR/XD

Ocular albinism
XR

Be Wise, Fool's GOLD Heeds
False Hope.
AR/AD/XR/XD

Lesch-Nyhan syndrome
XR

Be Wise, Fool's GOLD Heeds
False Hope.
AR/AD/XR/XD

Duchenne's muscular dystrophy
XR

Be Wise, Fool's GOLD Heeds
False Hope.
AR/AD/XR/XD

Hemophilia A and B
XR

Be Wise, Fool's GOLD Heeds
False Hope.
AR/AD/XR/XD

Fabry's disease
XR

Be Wise, Fool's GOLD Heeds
False Hope.
AR/AD/XR/XD

Hunter's syndrome
XR

Be Wise, Fool's GOLD Heeds
False Hope.
name the XR disorders
Be Wise, Fool's GOLD Heeds
False Hope

Bruton's agammaglobulinemia, Wiskott-Aldrich syndrome, Fragile X, G6PD deficiency, Ocular albinism, Lesch-Nyhan syndrome, Duchenne muscular dystrophy, Hemophilia A and B, Fabry's disease, Hunter's syndrome.
Adult polycystic kidney
disease

presentation
Always bilateral, massive enlargement of kidneys due to multiple large cysts. Patients
present with pain, hematuria, hypertension, progressive renal failure.
Adult polycystic kidney
disease

specific genetics
are due to mutation in APKD1 (chromosome 16)
Adult polycystic kidney
disease

associations
Associated with polycystic liver
disease, berry aneurysms, mitral valve prolapsediverticulosis
Familial hypercholesterolemia
(hyperlipidemia type IIA)

clinical findings
severe atherosclerotic disease early in life, and tendon xanthomas (classically in the
Achilles tendon); MI may develop before age 20.
Familial hypercholesterolemia
(hyperlipidemia type IIA)

lab findings
Elevated LDL owing to defective or absent LDL receptor. Heterozygotes (1:500) have cholesterol ≈ 300 mg/dL. Homozygotes (very rare) have cholesterol ≈ 700+ mg/dL,
Marfan’s syndrome

Skeletal abnormalities
tall with long extremities (arachnodactyly), pectus
excavatum, hyperextensive joints, and long, tapering fingers and toes (see Image
109).
Marfan’s syndrome

vascular findings
Cardiovascular––cystic medial necrosis of aorta → aortic incompetence and
dissecting aortic aneurysms. Floppy mitral valve.
Marfan’s syndrome

ocular findings
Ocular––subluxation of lenses.
Neurofibromatosis type 1
aka
von Recklinghausen’s disease
von Recklinghausen’s disease
aka
Neurofibromatosis type 1
Neurofibromatosis
type 1 (von Recklinghausen’s
disease)

findings
café-au-lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas). Also marked by skeletal disorders (e.g., scoliosis), optic pathway
gliomas, pheochromocytoma, and ↑ tumor susceptibility.
due to mutation in APKD1 (chromosome 16)
Adult polycystic kidney
disease
café-au-lait spots, neural tumors, Lisch nodules (pigmented iris
hamartomas). Also marked by skeletal disorders (e.g., scoliosis), optic pathway
gliomas, pheochromocytoma, and ↑ tumor susceptibility.
Neurofibromatosis
type 1 (von Recklinghausen’s
disease)
what are Lisch nodules
pigmented iris hamartomas seen in Neurofibromatosis
type 1
Neurofibromatosis
type 1 (von Recklinghausen’s
disease)

specific genetics
On long arm of chromosome17; 17 letters in von Recklinghausen or Neurofibromatosis
On long arm of chromosome17
Neurofibromatosis

17 letters in von Recklinghausen or Neurofibromatosis
Neurofibromatosis type 2

clinical findings
Bilateral acoustic neuroma, juvenile cataracts
Neurofibromatosis type 2

specific genetics
NF2 gene on chromosome 22;
type 2 = 22.
NF2 gene on chromosome 22;
Neurofibromatosis type 2

type 2 = 22
Tuberous sclerosis

findings
Findings: facial lesions (adenoma sebaceum), hypopigmented “ash leaf spots” on skin,
cortical and retinal hamartomas, seizures, mental retardation, renal cysts, cardiac
rhabdomyomas. Incomplete penetrance, variable presentation.
facial lesions (adenoma sebaceum), hypopigmented “ash leaf spots” on skin, cortical and retinal hamartomas, seizures, mental retardation, renal cysts, cardia