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More Free USMLE , MCCEE ,MCQe and AMQ Flashcards

what is the rate limiting reaction in


HMG Co reductase
cholesterol synthesis?

name this condition

mousy odor, tyrosine missing,


hence it must be supplied in the PKU
diet, can diagnose by **no nutrasweet!!!
amniocentesis and finding the
abnormal gene; eliminate
phenylalanine from diet
inability to phsophorylate the
mannose residues of potential
lysosomal enzymes located in
what is I cell disease? Golgi apparatus, hence they
cannot be taken up by the
lysosomes to degrade complex
substrates

explain the number of glucoses 4 glucoses, each glucose


necessary to build palmitic acid a produces 2 acetyl CoA the latter
16 carbon compound containing 2 carbons each

decreased glycolysis,
what is the result of a lack of
glycogenesis, fatty acid synthesis,
insulin in DKA?
storage of fat in adipose
alcohol and salicylates

name some uncoupling agents and produces brown fat from increased
explain what they do heat from reactions trying to
increase the generation of more
protons to make ATP
decreased glucose 6-phosphatase
(gluconeogenic enzyme) with
decrease in glucsose (fasting
hypoglycemia) and increase in
glucose 6-phosphate with
what is Von Gierke's disease?
production of normal glycogen in
the liver and kidneys; stimulation
tests with glucagon, fructose, etc.
cannot increase the glucose levels
owing to the missing enzyme

explain the biochemical processes urea cycle, heme synthesis,


in both cytosol and mitochondria gluconeogenesis

what dietary alteration would you decreased phenylalanine


suggest for a female that has (essential AA) and tyrosine (not an
pheochromocytoma? essential AA) in the diet

low in phenylalanine and high in


how would you counsel a patient tyrosine-->avoid nutrasweet since
with PKU who was pregnant? it contains aspartate and
phenylalanine

SXR with absent HGPRT, self


what is Lesch Nyhan? mutilation, hyperuricemia, mental
retardation
only in the liver
High Vm and high Km, not
inhibited by glucose 6-phosphate
where is glucokinase located?
hexokinase, in all tissues inhibited
by glucose 6-phosphate; low Vm
and low Km

what tissue can metabolize


branched chain amino acids in only muscle
maple syrup urine disease?

know glycogenolysis! .....

fructose 1, 6 bisphosphatase
what is the key enzyme in
catalyzes the conversion of
gluconeogenesis?
fructose 1,6-bisphosphate to
fructose 6-phosphatase

liver, kidney, intestinal epithelium


what the locations of glucose 6-
(lesser extent than others) absent
phosphatase?
in von Gierke's disease!

what does the carnitine shuttle


even chained fatty acids
carry?

what does the malate shuttle


NADH
carry?
vitamin D synthesis, other steroid,
what are the functions of LDL? cell membranes, synthesis of bile
salts/acids

FA syntheisis
CH synthesis
Uses of acetyl CoA? ketone body synthesis
***not a substrate for
gluconeogenesis
competitive vs. non-competitive
inhibitors, competitive (i.e. alcohol
dehydrogenase binding ethanol,
methanol, ethylene glycol at the
same binding site) has no change
in Vm but an increase in Km (lower
affinity for ethanol, increasing
ethanol reverses the inhibtion)
non-competitive inhibitor
discuss Km and Vmax Lineweaver
(organophosphates and effect on
Burke
acetylcholinesteratse does not
bind to the same site as
acetylcholine, binds to another site
on the enzyme that decreases
velocity of the reaction) has a
decrease in Vm, but the Km
remains the same, since the
substrate still binds to the normal
site

what is the relationship between


fatty acid length and energy ....
production?
what is the method of eliminating urea cycle
ammonia? **located in the hepatocyte

what is the differential if


epinephrine is given and only small debrancher deficiency
branched chains found?

draw cholesterol synthesis -----

what is the rate limiting step in


glycogen phosphorylase
glycogenolysis?

what is the origin of apolipoprotein


liver
100?

what is the origin of apolipoprotein


intestine
48?

liver cannot activate acetoacetate


in the mitochondria which requires
what is the reason why liver can succinyl CoA; acetoacetate CoA
not use ketones for fuel? transferase (a thiotransferase
enzyme) in order to convert AcAc
into acetoacetyl CoA
absent muscle phosphorylase,
what is wrong in McArdles increased glycogen in muscle, no
disease? increase in lactic acid after
exercise
folate because alcohol increases
loss of folate in urine and stool
which offsets the amount of folate
A pregnant woman is a beer
present in beer; furthermore she
drinker---> what supplements does
would probably be taken off beer
she need?
because of fetal alcohol syndrome
and would need folate; iron is not
affected by beer drinking

what is the key hormone of the fed


insulin
state?

what is the key hormone of the


glucagon
fasting state?

know all the lysosomal storage


....
diseases

mannose 6-phosphate is involved


mannose 6-phosphate is involved in transfer of dolichol (lipid) in the
in what? RER in the synthesis of O-linked
glycosides
what are the reactions involving
...
NAD/NADH and NADP/NADPH?

HMP shunt; malate


what is the major source of dehydrogenase reaction to a
NADPH? lesser extent; NADPH supplies
reducing equivalents
Mutation changes an amino acid one with the most negative
sequence--> which one would charges (most acidic) glutamine;
have the greatest effect on one that would remain closest to
migration in a serum protein the anode (negative pole) is the
electrophoriesis? most basic amino acid--arginine
increased beta-oxidation of fatty
what is the mechanism of acids and production of acetyl CoA
ketoacidosis in DKA which is used by the liver to
synthesize ketone bodies

linear gene drawing with labels;


where is the promotor location?
pick upstream location

what is the energy source for


GTP
protein synthesis?

LDH
what isoenzymes have 2 genes
and 4 subunits? 5 isotypes = LLLL, LLLH, LLHH,
LHHH, HHHH
name the second messanger
cGMP
atrial natriuretic peptide

name the second messanger


tyrosine kinase
insulin

name the second messanger


ion channels
nicotinic

what is the best method of


restriction fragment lenght
detecting relatedness of a new
polymophism
bacteria?

what is the enzyme used for PCR? DNA polymerase

what is the source of glucose in a alanine--> transaminated into


brain in starvation? pyruvate

carriers ammonia in nontoxic form


what is the purpose of glutamine?
**most abundant amino acid
synthesis of melanin, synthesis of
neurotransmitters (dopamine, Nor,
what is the purpose of tyrosine?
Epi) decreased in PKU (must
supply tyrosine in diet)
inhibitory neurotransmitter blocked
by tetanus toxin, synthesis of delta
what is they purpose of glycine? aminolevulinic acid in heme
synthesis, synthesis of bile
acid/salts
increased in aromatic amino acids-
-> phenylalanine, tyrosine,
tryptophan (menonic PTT) leads to
increased synthesis of false
what is the biochemistry of hepatic neurotransmitters (GABA,
encephalopathy? ocopamine) in hepatic
encephalopathy; branched chain
amino acids inhibit synthesis of
false neurotransmitters---reason
why they are given for treatment
Acid yields H+ and its conjugate
base.
Acid dissociates in water to yield
_____ and ______.
Base combines with H+ to form its
conjugate acid.
Base combines with _____ in
water to form ______.
(Acid=proton donor, base=proton
acceptor)
Acidic dissociation constant Ka
Ka=k(1)/k(-1)=[H+][A-]/[HA]
(formula)
Stronger acids have higher Ka
Strong acid has a high/low Ka?

pKa= -log(Ka)
pKa
Strong acid: pKa<2
Strong acid has high/low pKa?
Weak acid: pKa>10
Henderson-Hasselbalch equation pH=pKa + log([A-]/[HA])

H1

(negatively charged DNA loops 2x


Which histone is not in the around the positively charged
nucleosome core? histone octamer (2 sets of H2A,
H2B, H3, H4). H1 ties the
nucleosome beads together in a
string.)

Condensed, transcriptionally
Heterochromatin
inactive (sterically inaccessible)

Less condensed, transcriptionally


Euchromatin
active (sterically accessible)

Purines
A, G
Which are purines?
2 rings
How many rings?

Pyrimidines
C, T, U (CUT the PY)
Which are pyrimidines?
1 ring
How many rings?
Deamination of _____ makes
Cytosine
uracil.

CG

Have 3 H bonds between them


Which nucleotides have a stronger
instead of just 2 in AG bonds
bond? Why?
(Higher G-C content=higher
melting point)
Nucleoside=base + ribose
Nucleoside?
Nucleotide=base + ribose +
Nucleotide? phosphate (linked by 3'-5'
phosphodiester bond)

Amino acids needed for purine Glycine, aspartate, glutamate


synthesis? (make up back bone of purines)

Guanine has a ______. Ketone

Thymine has a _______. Methyl


Converson of 5'-phosphoribosyl-1-
pyrophosphate (PRPP) to 5'-
phosphoribosyl-1-amine

Committed step of de novo purine Enzyme: glutamine PRPP


nucleotide synthesis amidotransferase

(Enzyme activated by PRPP and


inhibited by the end products:IMP,
GMP, and AMP)
GTP is a substrate of AMP
synthesis and ATP is a substrate
Reciprocal substrate effect: how for GMP synthesis
does it balance the supply of
purine nucleotides? Both AMP and GMP are made
from IMP and can convert back to
IMP
Aldehydes or ketones
Monosaccharides (simplest
carbohydrates) are _____ or
(glucose is an aldose, fructose is a
_____.
ketose)
Pyranose=6 membered ring
Pyranose sugars contain a (#)
(glucose, galactose)
membered ring whereas furanose
sugars contain a (#) membered
Furanose=5 membered ring
ring
(fructose, ribose, deoxyribose)

Ascorbic acid (vitamin C)


Deficiency of this monosaccharide
derivative causes scurvy
Needed to synthesize collagen

Monosaccharide derivative needed


to form direct bilirubin and Glucuronic acid
glycosaminoglycans (GAGs)
Sorbitol
Which sugar alcohol derived from
(osmotic damage in
glucose leads to osmotic damage
lens=cataracts, Schwann
of tissues in diabetes mellitus?
cells=peripheral neuropathy,
pericytes=retinopathy)

Maltose= ____ + _____ Glucose + glucose

Lactose= ____ + _____ Glucose + galactose

Sucrose= _____ + ______ Glucose + fructose

Enzyme to digest starch


Amylase
(polysaccharide)

Glycogen phosphorylase cleaves


Enzyme to cleave glycogen at alpha-1,4 linkages to release
glucose units
Supplies no energy; human
digestive enzymes cannot
hydrolyze BETA-1,4 linkages
(insoluable fiber)
Cellulose
Human enzymes cleave other
polysaccharides like glycogen and
starch at alpha-1,4 linkages.
This and other GAGs are
negatively charged
Hyaluronic acid
polysaccharides that form a major
part of ECM

Simplest lipids Fatty acid

Only 2 fatty acids that are essential


Linoleic and linolenic
(must be supplied in diet)

Most are even


Do most fatty acids have an
even/odd # of carbon atoms?
Vit B12 (methylmalonyl-CoA
mutase requires B12 as a cofactor.
What is required for metabolism of
If no B12, methylmalonyl-CoA
odd chained fatty acids?
accumulates and damages myelin)

Unsaturated fatty acids contain


Double bonds
one or more _____ ____.
Atherosclerosis
Trans fatty acids are a risk factor
(Naturally occurring unsaturated
for ________.
fatty acids have the cis
configuration)
Fluidity of cellular membranes
correlates _____
(inversely/directly) with melting Inversely
point of fatty acids in membrane
phospholipids?
Increased cytosolic Ca2+ activates
Phospholipase A2
__________ which causes cell
membrane damage in tissue
Corticosteroids inactivate
hypoxia.
phospholipase A2 thereby
decreasing release of arachidonic
What effect do corticosteroids
acid.
have in this process?
Lung surfactant
Respiratory distress syndrome is
associated with a deficiency of (decreases surface tension; often
_______. in deficient in premies and infants
of diabetic moms)
Hereditary defects in lysosomal
enzymes that degrade
sphingolipids (mainly found in
Sphingolipidoses (mechanism,
white matter of CNS).
examples)
Tay-Sachs disease, Gaucher's
disease
Myelin sheath (all are
Where are sphingomyelins,
sphingolipids)
cerebrosides, and gangliosides
found?
(sphingomyelins are also in blood)
Steroid hormones
Cholesterol is a precursor for what
Vitamin D (skin derived)
3 things?
Bile acids

Short range, short term signaling


molecules.

3 types are made from


Eicosanoids
arachadonic acid:
Prostaglandins (cyclooxygenase)
Thromboxanes (cyclooxygenase)
Leukotrienes (lipoxygenase)
Cyclooxygenase

Effects (vary by tissue)


1) Promote acute inflammation
(increase vasodilation, inflam
response=PGE2)
Prostaglandins
2) Vasodilation of afferent arteriole,
vasoconstriction of cerebral
Derived from AA by which
vessels
enzyme?
3) Increase mucous barrier of
Major effects?
stomach (ulcers if too much
Inhibited by?
NSAIDs)
4) Decrease platelet aggregation
(PGI2)
5) Uterine contraction

Inhibited by aspirin, NSAIDs


Cyclooxygenase

Thromboxane A2 1) Platelet aggregation


2) Vasoconstriction
Derived from AA by which 3) Bronchoconstriction
enzyme?
Major effects? Cyclooxygenase inhibited by
Inhibited by? aspirin (permanent inhibition of
production in platelets) and
NSAIDs
Lipoxygenase

LTB4:
Leukotrienes
1) Neutrophil chemotaxis and
adhesion
Derived from AA by which
LTC4, LTD4, LTE4:
enzyme?
2) Bronchoconstriction
Major effects?
3) Vasoconstriction
Inhibited by?
4) Increase vascular permeability

Zileuton (inhibits lipoxygenase)


L isomer (D is found in bacterial
cell wall and some antibiotics)
Proteins are made of the L or D
isomer of amino acids? (Asymmetry of alpha-carbon gives
rise to these 2 optically active
isomers)
Isoleucine, leucine, valine
Which 3 amino acids are increased
in maple syrup urine disease?
All are branched chain amino acids
What property do they have in
(hydrophobic aa's with nonpolar
common?
side chains)

Which aa accumulates in
Phenylalanine accumulates;
phenylketonuria (PKU)? Which aa
tyrosine must be supplied
must be supplied?
Arginine and histidine
Which aa's stimulate growth
hormone and insulin?
(needed for growth in children)

Catecholamines, melanin, thyroid


Tyrosine is a precursor for what 3 hormones
things?
(Ty)

What information would an ELISA It would tell you whether a certain


using a test antigen coupled to a antibody is present in the patient's
color-generating enzyme give you? blood

True or False: Enzyme-linked


immunosorbent assay tests True
antigen-antibody reactivity

What information would an ELISA It would tell you whether a certain


using a test antibody coupled to a antigen is present in the patient's
color-generating enzyme give you? blood

Identify the technique: A test


antigen that is labeled with a color-
generating enzyme can be used to
Enzyme-linked immunosorbent
determine the presence of a
assay (ELISA)
specific antibody. If the antibody is
present, the solution will have an
intense color reaction.
The FISH analysis allows
researchers to identify anomalies
What is the advantage of a FISH
at a molecular level, including
analysis over a karyotype?
deletions that are too small to see
on a karyotype
What laboratory technique is
represented with the acronym Fluorescent In Situ Hybridization
FISH?

Basic aa's have a ______ (+/-)


Positive charge
charge at pH 7

Would lysine, arginine, or histidine Positive


have a positive or negative charge
at physiological pH? (these are basic aa's)

Would aspartate or glutamate have Negative


a positive or negative charge at
physiological pH? (these are acidic aa's)

pI is the isoelectric point (pH at


What is pI? which the amino acid has zero net
charge)
When pI>pH, the net charge on
the molecule is ___ (+/-) When pI>pH, the aa has a positive
net charge.
Collagen
Hydroxylation of proline and lysine
is important to form _____. What
Vitamin C is needed for
cofactor is needed for this
hydroxylation (hydroxyproline and
reaction?
hydroxylysine)

Precursor amino acid for serotonin,


Tryptophan
niacin, melatonin
Glycosylation of proteins (i.e.
hemoglobin and vessel basement
Diabetes mellitus
membranes) occurs in which
disease?

Secondary
alpha-helix and beta-pleated sheet
are examples of ________
(primary structure determines
structure
secondary and tertiary structures)
False, this is tertiary
T/F Quaternary structure is the 3-D
folded structure of a polypeptide (quaternary is the organization of
(native conformation) multiple polypeptide chains, i.e.
dimers, tetramers)
Leucine zippers and zinc fingers
are common supersecondary
DNA-binding proteins
structures found in _____-binding
proteins

Lactic acid accumulation (low pH


In tissue hypoxia, what leads to denatures proteins)
denaturation of enzyme and
coagulation necrosis? (Heavy metals denature stabilizing
bonds in proteins too)
In glucose-6-phosphate
dehydrogenase deficiency,
peroxide
increased ________ in RBCs
leads to Hb denaturation.
Some enzymes need cofactors or
Coenzyme=nonprotein organic
coenzymes. Which one is a...
molecule (i.e. vitamin derivatives)
nonprotein organic molecule?
Cofactor=metal ion
metal ion?
Km=substrate concentration at
which reaction velocity is 1/2 Vmax
What is Km? What does a high Km
indicate about an enzymes affinity
High Km indicates low enzyme
for substrate?
affinity for substrate (takes more
substrate to reach certain velocity)
In a zero order enzyme catalyzed
reaction, velocity is _______ of [S]. Independent

In a first order reaction, velocity is Proportional


_______ to [S].
Km increases/decreases?
Increases (less enzyme affinity for
substrate)
Competitive inhibition:
Vmax increases/decreases?
Km increases/decreases? Unchanged
Vmax increases/decreases?
Can increased substrate reverse
Can increased substrate reverse inhibition? Yes
inhibition?
Examples? Examples? Methotrexate (inhibits
dihydrofolate reductase), alcohol
(competes with methanol/ethylene
glycol)
Non competitive inhibitors:
Km unchanged
Km increases/decreases? Vmax decreased
Vmax increases/decreases?
Can't be reversed with increased
Can be reversed by increased substrate
substrate?

Heavy metals, aspirin, flurouracil,


and organophosphates are all irreversible
________ enzyme inhibitors
How would the following affect
AST and ALT levels in serum?
Viral hepatitis: ALT>AST
Alcoholic hepatitis: AST>ALT
Viral hepatitis
MI: AST only
Alcoholic hepatitis
MI
Hbg is for O2 transport, Mbg is for
O2 storage

Hemoglobin vs. myoglobin Hbg in RBCs, Mbg in muscle

Function? Hbg has 4 heme groups, Mbg has


Location? 1
# heme groups?
Saturation at PO2 in tissues? Hbg has low sat in tissues, Mbg
Cooperative binding? has high sat (only release O2 if
tissues hypoxic)

Hbg yes, Mbg no


Paternal allele is deleted or
In Prader-Willi syndrome, the allele
mutated (chr15q partial deletion)
from which parent is
deleted/mutated? Which parent's
Maternal allele is imprinted
allele is imprinted?
(silenced) normally
Maternal allele is mutated/deleted
In Angelman syndrome, the allele
(chr15)
from which parent is
deleted/mutated? Which parent's
Paternal allele is imprinted
allele is imprinted?
(silenced) normally

What form of iron is normally found


Reduced form (Fe2+)
in RBCs and can bind O2?
Oxidized form (Fe3+); causes
cyanosis b/c can't bind O2 so O2
sat decreases (can cause other
What form of iron is found in symptoms like dyspnea and coma
methemoglobin? What does this at higher concentrations)
cause?
(Can be caused by chemicals, like
nitrates, or inherited conditions,
like G6PD deficiency)

Decrease it (methemoglobin can't


How do CO and methemoglobin
bind O2, hemo/myoglobin have
affect O2 saturation?
much greater affinity for CO)

How do you treat CO poisoning? 100% O2 or hyperbaric O2

Left shift indicates increased


affinity for O2 (promotes O2
loading)
What does a left shift in the O2
binding curve indicate about Hb
1) Methemoglobin
affinity for O2?
2) CO
3) HbF
What causes a left shift?
4) Decreased CADET (low pCO2,
low acid (alkalosis), low 2,3 DPG,
low temp)
Right shift indicates a decreased
Hb affinity for O2 (promotes
unloading O2)
What does a right shift in the O2
binding curve indicate about Hb 1) High pCO2
affinity for O2? 2) High acid (acidosis)
3) High 2,3 DPG
What causes a right shift? 4) Exercise
5) High temp

CADET

What is the major vehicle for


Bicarb
carrying CO2 in blood?

Diabetes mellitus ( >5%)


HbA1c (glycosylated HbA) is high
(indicates levels of blood glucose
in what disease?
for about last 120 days; marker for
long-term glycemic control)

Does HbF increase/decrease


sickling in patients with sickle cell Decrease
anemia?

Patients with sickle cell trait are O2 tensions are low enough to
usually asymptomatic except in the induce sickling and renal damage
renal medulla. Why? (renal papillary necrosis)

Causes: nitrate compounds,


sulfonamides, aniline dyes
What causes acquired
(convert to Fe3+)
methemoglobinemia?
Treatment: IV methylene blue
How do you treat it?
(primary), vitamin C (ancillary);
help reduce Fe3+ to Fe2+
What aa is every third aa in
collagen?
Glycine
What is needed to hydroxylate
Vitamin C
lysine and proline to promote cross
bridging?
What disease involves a defect in
collagen
synthesis/secretion/degredation,
Ehlers-Danlos syndrome
loose skin, hyper elastic skin,
aortic aneurysms, and colon
rupture?
Osterogenesis imperfecta
Decreased synthesis of type 1 (autosomal dominant)
collagen, pathogenic fractures,
blue sclera (blue sclera=seeing choroidal
veins under the thin sclera)
Sex-linked dominant disorder
caused by defective type IV
collagen. Glomerulornephritis, Alport's syndrome
sensorineural hearing loss, ocular
defects.

Tensile strength of collagen


weakened due to lack of cross- Scurvy (vit D deficient)
bridges

T/F Cholesterol is found only in the


False, cholesterol is found in the
outer lipid monolayer of the
outer and inner monolayers
membrane lipid bilayer.
Do the following increase or
decrease membrane fluidity?
Do the following increase or
Long-chain saturated fatty acids:
decrease membrane fluidity?
Decrease
Long-chain saturated fatty acids
Cis unsaturated fatty acids:
Cis unsaturated fatty acids
Increase
Cholesterol
Higher temperatures
Cholesterol: Decrease

Higher temperatures: Increase


Requires transport protein? Yes
Works against gradient? No
Facilitated diffusion:
Coupled to ATP hydrolysis? No
Requires transport protein?
(Passive moves down
Works against gradient?
concentration gradient. If works
Coupled to ATP hydrolysis?
against a gradient, needs ATP
either directly or indirectly)
Requires transport protein? Yes
Primary active transport:
Works against gradient? Yes
Coupled to ATP hydrolysis? Yes
Requires transport protein?
(directly; indirect in secondary
Works against gradient?
active transport)
Coupled to ATP hydrolysis?
Powered by movement of
Powered by movement of
cotransported ion? No (true for
cotransported ion?
secondary active)
In tissue hypoxia, the decrease in
ATP production allows ____ to
Ca2+; no ATP means Ca-ATPase
come into the cell and activate
stops working and Ca can come in.
phospholipases & caspases
leading to irreversible cell damage.
Dysfunciton in exocrine glands
leading to high Na/Cl in sweat,
highly viscous obstructive mucous,
Cystic fibrosis
malabsorption, and recurrent
Pseudomonas aeruginosa
CFTR defect (CFTR is a Cl
respiratory infections.
ATPase pump)
Which disease?
What's the defect?
Cystinuria
Cystine kidney stones (cystine has
hexagon shaped crystal in urine)
Autosomal recessive (messed up
carrier protein that mediates
Which disease?
resorption of dibasic amino acids
What's the inheritance?
like cystine)
Pellegra-like symptoms (diarrhea,
dermatitis, dementia); impaired
Hartnup's disease
absorption of tryptophan reduces
synthesis of niacin

Familial hypercholesterolemia Autosomal dominant


Lack low-density lipoprotein (LDL)
Inheritance? receptors
Lacking which receptor's function? At risk for early MI/stroke b/c
Susceptible to? premature atherosclerosis
GTP; GDP
Trimeric G proteins are in the
active state when bound to ____ (In the GTP bound state, the alpha
and an inactive state when bound subunit (G-alpha) either
to _____. stimulates/inhibits an effector
protein)

What effect does the G protein


Stimulates adenylate cyclase to
alpha subunit Gs have on its
increase cAMP
second messenger?
What effect does the G protein
Inhibits adenylate cyclase to
alpha subunit Gi have on its
decrease cAMP
second messenger?

What effect does the G protein


Stimulates phospholipase C to
alpha subunit Gq have on its
increase IP3 and DAG
second messenger?

The Gq subunit activates


IP3 stimulates release of Ca2+
phospholipase C, which activates
from the ER
PIP2 increasing IP3 and DAG.
DAG activates protein kinase C
What do IP3 and DAG do?

What happens when ligand binds


Autophosphorylation (activates)
receptor tyrosine kinase?

Steroid hormones bind to


receptors in the _____ and the
Cytosol; nucleus
hormone receptor complex moves
to the _______.

Nucleus (receptor has a hormone-


Tyroxine and retinoic acid have
binding domain and a DNA-binding
receptors in the _______.
domain)

Gs; resulting increase in cAMP in


Cholera permanently activates ___ intestinal mucosa causes a
(G protein alpha subunit) by secretory diarrhea with a loss of
catalyzing ADP ribosylation of the isotonic fluid
subunit. What symptom does this
cause? (enterotoxigenic E. coli toxin also
activates Gs)
Pertussis toxin permanently
inhibits ___ (G protein alpha Gi; resulting increase in cAMP
subunit) by catalyzing ADP increases mucous secretion in
ribosylation of the subunit. What respiratory tract (whooping cough)
symptom does this cause?
IgG autoantibody against TSH
receptors producing
Graves' disease
hyperthyroidism.
Type II hypersensitivity
What disease?
What type of hypersensitivity rxn?
If low GTPase activity, always
bound to GTP thus always active.
Ras oncogene encodes a mutant
Ras protein with very low GTPase (Ras is a type of G protein that
activity. How does this contribute functions in signaling pathway from
to increased cell proliferation? receptors like epidermal growth
factor and platelet-derived growth
factor receptor.)
Basal metabolic rate (~60% of
daily expenditure; determined
mostly by weight)
Energy consumption of individual
at rest
Daily energy expenditure= BMR +
thermic effect foods + physical
activity
Where are the following found in
Amylase=saliva & pancreatic
the GI tract?
secretions
Lactase, sucrase,
Amylase
maltase=intestinal brush border
Lactase
(damage or loss of enzymes can
Sucrase
cause osmotic diarrhea)
Maltase
1) increase intestinal motility/soften
stool
2) decrease risk of colon cancer by
absorbing lithocholic acid
3) reduce absorption of
Functions of insoluble fiber
cholesterol, fat soluable vitamins

(Insoluable fiber has beta-1,4


glycosidic linkages which can't be
hydrolyzed by amylase)
# of double bonds in...
1
monounsaturated fat?
2+
polyunsaturated?
0
saturated?
Linoleic (omega 6) & linolenic
(omega 3)

Essential fatty acids Functions: 1) maintain fluidity of


cellular membranes 2) make
What are they? arachidonic acid (from linoleic) 3)
Function? prevent platelet aggregation
Deficient? (linolenic)

Deficient: scaly dermatitis, poor


wound healing, hair loss
Tiny globule containing lipids that
are resorbed into intestinal
mucosal cells via passive diffusion
What's a micelle?
(contain 2-monoaclyglycerol + FFA
(triacylglycerol), phospholipids, vit
DAKE, free cholesterol)
Pancreatic lipase breaks it into 2-
monoaclyglycerol + FFA which
gets absorbed into mucosal cells in
How is triacylglycerol absorbed by a micelle. Reformed into
the gut? triacylglycerol in the nascent
chylomicron and goes into
lymphatics (major source of energy
to cells)

Pancreatic insufficiency
3 major categories for fat
Poor bile salt resorption/deficiency
malabsorption (steatorrhea)
Small bowel disease

Carbohydrates (salivary amylase


What would still be absorbed and disaccharidases in brush
normally in pancreatic border is enough)
insufficiency?
Fat and protein malabsorbed

Micellarization of fats
Bile salt function
(lack causes steatorrhea)

1) Liver cirrhosis (can't make it


from cholesterol)
2) Terminal ileum
disease/removed (can't resorb)
Causes of bile salt deficiency
3) Excess binding of bile salts
(cholestyramine)
4) Bacterial overgrowth (destroys
bile salts)
1) Diarrhea, anemia, malnutrition,
weight loss
Characteristic clinical findings in
2) Night blindness (vit A), rickets
malabsorption
(vit D), hemorrhagic diathesis, GI
bleeds (vit K)
Begins in stomach: pepsin (chief
cells), acid denatures (parietal
cells)

Pancreas: trypsin and other


proteases
What is needed to digest proteins?
Intestinal epithelial cells:
peptidases

Uptake into portal circulation:


carrier protein requires ATP to
transport aa's from lumen to circ.
Urea
When amino acids are oxidized
their nitrogen atoms are fed into (excreted in urine; people in renal
the _____ cycle in the liver. failure should eat low protein diet
so make less urea)
Nitrogen balance= amount of
nitrogen (protein) consumed -
amount of nitrogen excreted
What's nitrogen balance? What
+ balance=new proteins being
would a positive nitrogen balance
made (i.e. pregnancy, growing,
indicate? Negative?
lactation, healing)

- balance=tissue protein
breakdown (i.e. burns)

Marasmus
Diet deficient in both proteins and
calories
(total calorie deprivation)

Extreme muscle wasting, growth


retardation, usually during 1st year Marasmus
of life from total calorie deprivation
1) Pitting edema/ascites
2) Enlarged fatty liver (decreased
apolipoproteins)
3) Anemia
Symptoms of Kwashiokor
4) Diarrhea (loss of brush border
enzymes)
5) Defects in cellular immunity
6) Less extreme muscle wasting

Diet deficient in protein but


Kwashiokor
adequate in calories (carbs)

Water soluble vitamins generally


function as ________ in enzymatic cofactors
reactions.

Churg-Strauss
p-ANCA Polyarteritis nodosa
Ulcerative colitis

c-ANCA Wegener's

Anti-double stranded DNA Systemic lupus erythematous


CREST Syndrome (calcinosis,
Raynaud's phenomenon,
esophageal motility syndrome,
Anticentromere sclerodactyly, telangiectasia)

Localized systemic sclerosis


(vasculotide)

Anti-DNA topoisomerase Diffuse systemic sclerosis

1) Energy metabolism (B1-3, B5,


biotin(B7))
2) Amino acid metabolism
4 categories of water soluble (pyriodoxine, pyridoxal,
vitamin function pyridoxamine (B6)
3) RBC/neural development
(folate, B12)
4) Collagen synthesis (vit C)
1) Wernike-Korsakoff
2) Peripheral neuropathy (dry
Deficiency of vitamin B1 (thiamine) beriberi)
3) Congestive cardiomyopathy
(wet beriberi)

Corneal neovascularization,
Deficiency of vitamin B2
glossitis, cheilosis, anglular
(riboflavin)
stromatitis

Pellagra (diarrhea, dermatitis,


Deficiency of B3 (niacin)
dementia)
Sideroblastic anemia, peripheral
Deficiency of vit B6 (pyridoxine)
neuropathy, convulsions

Loss of ATP from dysfunction of


pyruvate and alpha-ketoglutarate
dehydrogenase reactions
Mechanism for clinical findings in
(normally gain 2 NADH)
thyamine (B1) deficiency
wet and dry beriberi (B1 used in
pyruvate dehydrogenase rxn)
Deficient in B1 (thiamine)

Can precipitate acute thiamine


Wernicke-Korsakoff syndrome
deficiency in alcoholics by giving
IV glucose (thiamine depleted by
pyruvate dehydrogenase reaction)
1) Diet deficient in niacin and
tryptophan
What can cause niacin (B3)
2) Tryptophan lost (Hartnup's dz.)
deficiency?
3) Typtophan used excessively
(carcinoid syndrome)
Cofactors in rxns to make ATP:
B1, B2, B3, B5, B7 (prime B's)
Deficiency in which water soluble
vitamins affect energy
(thiamine, riboflavin, niacin,
metabolism?
pantothenic acid, biotin
respectively)
_________ is a water soluble
vitamin that is part of the citric acid
Riboflavin (B2)
cycle and the electron transport
chain.
NAD+ (rxns with this are catabolic,
i.e. glycolysis)
What are the 2 active forms of
niacin?
NADP+ (anabolic, i.e. fatty acid
synthesis)
B6 (pyridoxine)
Isoniazid therapy can cause
deficiency of what vitamin? (Alcoholics and babies who drink
only goat's milk)
1) Removes methyl from N-
methyltetrahydrofolate to make
dTMP for DNA synthesis
-W/o it, megaloblastic anemia
(folate too)

2) Transfers methyl groups to


homocysteine to make methionine
-W/o it, high
Function of vit B12 (cobalamin)
homocysteine=thrombosis risk
(folate too)

3) Odd chain fatty acid metabolism


(cofactor to convert methylmalonyl
CoA to succinyl CoA)
-Accumulation of methylmalonyl
CoA converts to methylmalonic
acid=neurotoxic (not folate!)
1) Diet (pure vegan)
2) Pernicious anemia (need
intrinsic factor for absorption in
terminal ileum)
3) Chronic pancreatitis (need
What can cause B12 deficiency? pancreatic enzymes to cleave R
factor from saliva so IF can bind)
4) Terminal ileal disease (Crohn's,
celiac)
5) Fish tapeworm
6) Bacterial overgrowth
1) Hemophilia A
2) Hemophilia B
3) Glucose-6-phosphate
dehydrogenase deficiency
Which enzymopathies (4) are X- 4) Lesch-Nyhan syndrome
linked recessive? (hypoxanthine-guanine
phosphoribosyltransferase
(HGPRT)

(usually enzymopathies are AR)


Random inactivation of one X
chromosome in women in each
somatic cell during
embryogenesis.
What's lyonization?
(Sometimes female carriers of X
linked diseases can have mild
symptoms if a large enough
proportion of the normal X has
been inactivated)
Condensed, drumstick-shaped
body of DNA seen in the periphery
What's a Barr body?
of nuclei in females; inactivated X
chromosome (lyonization)
1) Enzymes (PKU, galactossemia,
Which general types of mutations
Tay-Sachs)
are inherited in an autosomal
2) Transport proteins
recessive pattern?
(thalassemias, cystic fibrosis)
1) Structural proteins (hereditary
spherocytosis, osteogenesis
Which general types of mutations imperfecta, Marfan's)
are inherited in an autosomal 2) Developmental gene expression
dominant pattern? (achondroplaia)
3) Metabolic receptors (familial
hypercholesterolemia)
DNA synthesis (tetrahyrofolate
receives a methylene group which
Functions of folate is then transfered by thymidylate
synthase to dUMP to make dTMP
for DNA synthesis)
Inhibits dihydrofolate reductase
(this enzyme usually converts FH2
How does methotrexate work?
to tetrahydrofolate (FH4) which is
needed for DNA synthesis)
1) methotrexate and trimethoprim
(both inhibit dihydrofolate
What substances can deplete
reductase)
folate?
2) Alcohol and oral contraception
(blocks resorption in intestine)

1) No neuro deficits
How do you differentiate folate
2) Normal levels of methylmalonic
deficiency from B12 deficiency?
acid

Where does biotin (B7) come


Bacterial synthesis in intestine
from?
1) Hydroxylation of lysine and
proline during collagen synthesis
2) Reduces non-heme iron (Fe3+)
to ferrous state (Fe2+) for
resorption (deficiency can also
Vit C is needed for...
cause IDA!)
(5 things)
3) Cofactor in conversion of DA to
norepi in catecholamine synthesis
4) Kepps tetrahydrofolate in its
reduced form
5) Antioxidant
liver; adipose tissue
Fat soluable vitamins are stored in
(function as hormones, cofactors,
____ and ______.
hemostatic agents and
antioxidants)

Beta carotenes (provitamin A)


Vitamin A (aka, retinol, retinal,
retinoic acid) is derived from
(too much beta can turn skin
_____.
yellow, but sclera white)

Vit A
Which vitamin is a component of
visual pigments in the rod?
(Def.=night blindness)

Night blindness (dry eyes, etc.)


Skin abnormalities (follicular
hyperkeratosis, dryness)
Vit A deficiency Lung abnormalities (bronchitis,
pneumonia, maybe cancer)
Growth retardation
Poor wound heal

Increased intracrainial pressure


Vit A excess (papilledema/convulsions); liver
tox; bone pain
Rickets (kids) osteomalacia
Vit D deficiency
(adults); hypocalcemia

Vit D excess Hypercalcemia (renal calculi)

Hemolytic anemia
Peripheral neuropathy
Posterior column degeneration
Vit E deficiency
(loss of vibratory, proprioception)
Retinal degen
Myopathy

Decreased synthesis of vit K


Vit E excess
dependent coagulation factors

Bleeding diathesis (GI,


Vit K deficiency
ecchymoses, prolonged PT)

Hemolytic anemia/jaundice in
Vit K excess newborn if mom has too much Vit
K
Endogenous: photoconversion of
7-dehydrocholesterol to vit D3

Exogenous absorbed in GI:


Plants=ergocalciferol (D2);
animals=cholecalciferol (D3)

1) D3 converted to 25-OH Vit D by


How is active vit D made?
25 hydroxylase in liver
2) 25-OH Vit D converted to 1,25-
OH Vit D by 1-alpha hydroxylase in
kidneys* (enhanced by PTH)

*macrophages can do this too so


people with sarcoidosis can get
hypercalcemic)
1) GI: resorb Ca and phosphorous
2) Kidney: increase resorb Ca
3) Bone: interacts w/receptors on
osteoblasts (mobilize alkaline
phosphatase, less bone
mineralization)
What's vit D do?
w/PTH vit D can
1) increase mobilization of Ca from
bone (stimulates conversion of
macrophage stem cells to
osteoclases)
2) Maintains serum Ca
concentration
Type 1: Deficiency of 1-alpha
hydroxylase
Type 1 vs. type 2 vit D deficiency
rickets
Type 2: Deficiency of vit D
receptors on target tissues
Most common cause vit D Renal failure (no 1-alpha-
deficiency hydroxylase)

Scavenges free radicals to


prevent...

Why is Vit E's antioxidant 1) oxidation of LDL (prevent


properties important? atherosclerosis)
2) oxidation of RBCs (prevent
hemolysis). Vit E protects
Erythrocytes
Gamma carboxylates them in the
liver so they can bind to Ca
What does vitamin K do to vit K (essential for clotting)
dependent coagulation factors?
Factors II, VII, IX, X, protein C & S
need this
Inhibits hepatic epoxide reductase
(reduces vit K to active form)
How does Coumadin work?
Factors II, VII, IX, X, protein C & S
need this

What do some newborns need to Vit K injections (lack bacteria in


prevent hemorrhagic disease of bowel and only have breast milk
newborn? which is poor in vit K)

Low serum H+ so H+ comes off


albumin exposing more sites for
How does an alkalotic state affect Ca to bind (less ionized Ca in
serum Ca? Symptoms? blood)

Tetany, etc.
Decrease total Ca w/o changing
How does hypoalbuminemia affect free ionized Ca.
serum Ca? Symptoms?
No symptoms
1) PTH: more resorb Ca in kidney;
release Ca from bone
2) Vitamin D: increases Ca resorb
How is Ca regulated (3)? in gut and kidney, mobilize Ca
from bone
3) Calcitonin (C cells in thyroid):
inhibits osteoclasts
PTH: binds osteoblasts to
stimulate osteoclasts (estrogen
inhibits this to prevent
What cells have receptors for PTH
osteoporosis!)
and calcitonin?
Calcitonin: binds osteoclasts and
inhibits them
1) Hypoalbuminemia (most
common; asymptomatic)
2) Hypomagnesemia (most
common pathologic cause; need
Mg for PTH secretion)
3) Vit D deficient
Causes of hypocalcemia
4) Primary hypoparathyroidism
(DiGeorge)

(tetany, Chvostek's sign,


carpopedal spasm, muscle
spasms)
1) Malignancy
2) Primary hyperparathyroidism
3) Sarcoidosis (granuloma
Causes of hypercalcemia synthesis of vit D)

(stones, groans, bones, psychiatric


overtones)
Addition of ______ (mineral) traps Phosphate
monosaccharides like glucose in
cells. (forms glucose-6 phosphate)

1) PTH increases release from


bone and increases excretion in
Control of phosphate kidneys
2) Vit D increase resorption from
small bowel

____ is needed for active transport


of glucose, galactose, and amino Na
acids in small intestine

1) Thiazide and loop diuretics


2) SIADH (resorb too much water
and dilute Na)
Causes of hyponatremia?
3) CHF/chronic liver disease:
Symptoms?
dilutional effect from retention

Cerebral edema, convulsions


1) Osmotic diuretics: mannitol
concentrates Na by losing free
water; excess urea and glucosuria
can do the same
Causes of hypernatremia? 2) Diabetes insipidus (no ADH
Symptoms? activity)

Mental status changes;


convulsions (similar symptoms to
hypoNa
Hypokalemia inhibits insulin
secretion; hyperkalemia promotes
How does hypokalemia affect
it
insulin secretion?
(insulin makes K go into cells)
Heart rate slows; stops in diastole
Symptoms of hyperkalemia?
(give insulin to drive K into cells)

Mg is cofactor of adenylate cyclase


involved in activation of PTH
How does Mg affect Ca in serum?
(increases PTH synthesis and
release) so increases Ca in serum
1) Alcoholism (most common;
causes increased renal loss)
2) Diuretics and other drugs that
Causes of hypomagnesemia?
increase renal loss

Can cause hypocalcemia (tetany)


1) Renal failure
2) Treatment of eclampsia with
magnesium sulfate
Causes of hypermagnesemia?
Symptoms?
Neuromuscular depression,
bradycardia (Mg needed for nerve
impulse propagation)
In the ferrous (Fe2+) state from
degraded heme. Most stored as
What form of iron is absorbed from apoferritin in enterocyte. Small
meat? Where does it go? amount is transfered to plasma
transferrin (circulatting binding
protein of iron)
ferritin
Serum _____ would be low in iron
deficiency. (serum ferritin reflects iron stores
in bone marrow)
When iron stores in
bone/macrophages are decreased,
liver produces ____(more/less) more
transferrin then increasing
_______(increasing/decreasing)
total iron binding capacity.
Newborn: bleeding Meckel's
Cause of iron deficiency in... diverticulum
Newborn? Child: bleeding Meckel's
Child? diverticulum; milk diet
Woman <50? Woman <50: Menorrhagia
Man <50? Man <50: Peptic ulcer dz.
Man/woman >50? Man/woman >50: Colon
polyps/cancer
1) Hemochromatosis
2) Hemosiderosis
Iron overload diseases? 3) Sideroblastic anemia (due to
pyridoxine def., lead poisoning,
alcohol)
Plummer-Vinson syndrome
(esophageal webs, glossitis, spoon
iron
nails, achlorhydria) results from
deficiency in ____.
poor wound healing; loss of taste
and smell
Zinc deficiency
(also perioral rash, hypogonadism,
growth retardation)

Microcytic anemia (decreased


Copper deficiency ferroxidase activity); dissecting
aortic aneurysm
Defect of secreting copper in bile Wilson's disease

Low serum ceruloplasmin Wilson's dz.

Iodine deficiency Goiter

Muscle pain/weakness
Cardiomyopathy
Selenium deficiency
Needed to make glutathione
(antioxidant)

Fluoride deficiency Dental caries

Impaired glucose tolerance;


Chromium deficiency
peripheral neuropathy

Negative
______(+/-) free energy changes
(delta G) allow coupled reactions
i.e. in metabolism, ATP hydrolysis
to proceed spontaneously in a
is coupled to an energetically
forward direction.
unfavorable reaction