Study your flashcards anywhere!

Download the official Cram app for free >

  • 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

1/613

Click to flip

613 Cards in this Set

  • Front
  • Back
full-term neonate of uneventful delivery becomes mentally retarded and hyperactive and has a musty odor. What is the d?
PKU
Stressed executive comes home from work, consumes 7 or 8 martinis in rapid succession before dinner, and becomes hypoglycemic. What is the mechanism?
NADH increase prevents gluconeogenesis by shunting pyruvate and oxaloacetate to lactate and malate
2 y/o girl has an increase in abd girth, failure to thrive and skin and hair depigmentation. What is the dx
kwashiorkor
alcoholic develops a rash, diarrhea, and altered mental status. What is the vitamen deficiency
vit B3 (pellagra)
51 y/o man has black spots in his sclera and has noted that his urine turns black upon standing. What is the dx
alkaptonuria
25 y/o male complains of severe chest pain and has xanthomas on his achilles tendons. What is the dz, and where is the defect?
familial hypercholesterolemia; LDL receptor
Condensed by (-) charged DNA looped twice around (+) charged H2A, H2B, H3, & H4 histone octamers (nucleosome bead). H1 ties nucleosmes together on a string (30-mm fiber). In mitosis, DNA condenses to form mitotic chromosomes.
Chromatin sx--image 77

note: Think of beads on a string
this type of chromatin is condensed, transcriptionally inactive
heterochromatin
this type of chromatin is less condensed, transcriptionally active
euchromatin

eu=true, "truely transcribed."
purines are _____ & _____ and have _____ ring/s.
pyramidines are _____,_____, &______
A,G (2 rings)
C,T,U (1 ring)

mneu: PURe As Gold: PURines.
CUT the PY (pie)
Guanine has a _______
ketone
Thymine has a ______
methyl

mneu: THYmine has a meTHYl
Deamination of cytosine makes a _____
uracil
uricil is found in this nucleic acid
RNA
thymine is found in this nucleic acid
DNA
This bond has 3 H bonds and is therefore stronger that this bond which only has 2 H bonds
G-C bond > A-T
nucleotides with a higher G-C means a higher this
melting temperature
nucleotides are linked by this type of bond
3'-5' phosphodiesterase bond
image p. 77 purines (A,G)
--
image p. 77 pyramidine (C,T,U)
--
this refers to substituting purine for purine or pyrimidine for pyrimidine
transition

mneu: TransItion=Identical types
this refers to substituting purine for a pyrimidine or pyrimidine for purine
Transversion

mneu: TransVersion=conVersion between types
this feature of the genetic code refers to the fact that each codon specifies only 1 amino acid
unambiguous
this feature of the genetic code refers to the fact that more than 1 codon may code for the same amino acid
degenerate
the genetic code is commaless, nonoverlapping (except some viruses) T or F
T
the genetic code is universal (exceptions include mitochondria, archaeobacteria, mycoplasma, and some yeast) T or f
T
this mutation in dna often involves the same AA, it is often a base change in the 3rd position of codon (tRNA wobble).
silent
this mutation in dna involves a changed AA (conservative-new AA is similar in chemical sx)
missense
this mutation in dna often involves a change resulting in an early STOP CODON
nonsense

mneu: stop the nonsense
this mutation in dna often involves a change resulting in misreading of all nucleotides downstream, usually resulting in a truncated protein
frame shift
Single origin of replication in prokaryotic DNA replication by DNA polymerases refers to ________ DNA synthesis on the leading strand and _______ on the lagging strand
Continuous
Discontinuous (Okazaki fragments)
DNA polymerase III has ____ synthesis and proofreads with ______ exonuclease
5'->3'

3'->5'
DNA polymerase I excises RNA primer with ____ exonuclease
5'-3'
these create a nicks in the helix to relieve supercoils
DNA topoisomerase
this makes an RNA primer on which DNA polymerase III can initiate replication
Primase
this elongates the chain by adding deoxynucleotides to the 3' end until it reaches primer of preceding fragment. 3' ->5' exonuclease activity "profreads" each added nucleotide.
DNA polymerase III
this degrades RNA primer
DNA polymerase I
this seals
DNA ligase
image p. 78 Prokaryotic DNA replication and DNA polymerases
--
eukaryotic genome has _____ origins of replications
multiple
replication begins at a consensus sequence of ____ base pairs
AT
eukaryotes have seperate polymerases ______ for synthesizing RNA primers, leading-strand DNA, mitochondrial DNA, and DNA repair
(αβδγε)
describe DNA repair of single strand
single strand, excision repair-specific glycosylase recognizes and removes damaged base. Endonuclease makes a break several bases to the 5' side. Exonuclease removes a short stretch of nucleotides. DNA polymerase fills gap. DNA ligase seals.
DNA repair defects regarding skin sensitivity to UV light results in this dz
xeroderma pigmentosum
DNA repair defects regarding x-rays results in this dz
ataxia-telangiectasia
DNA repair defects regarding radiation results in this dz
Bloom's syndrome
DNA repair defects regarding cross-linking agents results in this dz
Fanconi's anemia
xeroderma pigmentosum is this inheritance
autosomal recessive
XP results in defective excision repair such as uvr ABC endonuclease. It results in inability to repair _____, which form in DNA when exposed to UV light.
thymidine dymers [image p. 79]
XP is associated w/ these things
dry skin, melanoma, & other CA
DNA & RNA are both synthesized in this direction
5' ->3'
The 5' of the incoming nucleotide bears the ______ . The 3' hydroxyl of the nascent chain is the target
triphosphate (energy source for bond

mneu: Imagine the incoming nucleotide bringing a gift (triphosphate) to the 3' host. "BYOP (phosphate) from 5 to 3"
Protein synthesis procedes in this direction
5' ->3'
amino acids are linked in this way
N to C
mRNA is the _____ type of RNA

rRNA is the most _____ type of RNA

tRNA is the ______ type of RNA
massive, Rampant, Tiny
In prokaryotes this makes all 3 kinds of RNA
RNA polymerase
In eukaryotes, ________ makes rRNA
RNA polymerase I

mneu: I,II, III are numbered as their products are used in protein sythesis
In eukaryotes, ________ makes mRNA
RNA polymerase II

mneu: I,II, III are numbered as their products are used in protein sythesis
In eukaryotes, ________ makes tRNA
RNA polymerase III

mneu: I,II, III are numbered as their products are used in protein sythesis
eukaryotic RNA polymerase has no ________ fx, but can initiate chains
proofreading fx
RNA polymerase II opens DNA at _________
promoter site (A-T rich upstream sequence ---TATA and CAAT).
this poison is found in death cap mushrooms and works by inhibiting RNA polymerase II
alpha-amantin
what is the mRNA initiation codon
AUG (or rarely GUG)

mneu: AUG inAUGurates protien synthesis
in eukaryotes AUG codes for this, which may be removed before translation is completed
methionine
in prokaryotes the initial AUG codes for ________
formyl-methionine (fmet)
Give stop codons
UGA,UAA,UAG

mneu: U Go Awau, U Are Away, U Are Gone
In the regulation of gene expression, this is the site where RNA polymerase and multiple other transcription factors bind to DNA upstream from gene locus
promotor
promoter mutation commonly results in this
dramatic decrease in amount of gene transcribed
In the regulation of gene expression, 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
In the regulation of gene expression, this is the site where negative regulators (repressors) bind.
operator
These contain actual genetic information coding for proteins
exons [image p. 80]

mneu: INtrons stay IN the nucleus, whereas EXons EXit and are EXpressed
These are intervening noncoding segments of DNA
introns

mneu: INtrons stay IN the nucleus, whereas EXons EXit and are EXpressed
Introns are precisely spliced out of primary mRNA transcripts. A lariat-shaped intermediate is formed. ___________ facilitate splicing by binding to primary mRNA transcripts and forming splicosomes.
small nuclear ribonucleoprotein particles (snRNP)
RNA processing in eukaryotes occurs in the _______, after transcription.
nucleus
only _______ is transported out of the nucleus
processed RNA
describe RNA processing in eukaryotes (3 steps)
[image p. 80]
1) capping on 5' end (7-methyl-G)
2) Polyadenylations on 3' end (-200 As)
3) Splicing out of introns
what is the initial transcript of RNA processing (eukaryotes) called
heterogeneous nuclear RNA (hnRNA)
capped and tailed transcript is called _______
mRNA
tRNA sx consists of 75-90 nucleotides, cloverleaf form, anticodon end is opposite 3' aminoacyl end. All tRNAs, both eukaryotic and prokaryotic, have CCA 3' end along w/ a high percentage of chemically modified bases. The amino acid is covalently bound to the ___ end of the tRNA.
3'
1 of these is used up per AA, it uses ATP and scrutinizes AA before and after it binds to tRNA. If incorrect, bond is hydrolyzed. The AA-tRNA bond has energy for formation of peptide bond.
Animoacyl-tRNA synthetase
A mischarged tRNA reads usual codon but inserts the ______
wrong AA
___________ and binding of charged tRNA to the codon are responsible for accuracy of amino acid selection
aminoacyl-tRNA synthetase
image tRNA charging [p. 81]
--
this describes how accurate base parining is required only in the 1st 2 nucleotide positions of an mRNA codon, so codons differing in the 3rd position may code for the same tRNA/amino acid
tRNA wobble
In ribosome protein synthesis Met sits in the ______ site
P site(peptidyl)
In ribosome protein synthesis, the incoming amino acid binds to the _____ site, hydrolyzing Met's bond to its tRNA while simulatneously forming a peptidyl bond between 2 amino acids.
A site (aminoacyl)
The ribosome shifts 1 codon towards the 3' end of the mRNA, shifting the uncharged tRNA into the __ position and the dipeptidyl tRNA into the __ site
E
P
ATP is used for this with tRNA
Activation (charging)
GTP is used for this with tRNA
Gripping and Going places (translocation)
enzyme kinetics [image p. 82]
--
the lower the Km, the _____ the affinity
higher
this type of inhibitor resembles substrate
competitive inhibitor
this type of inhibitor can be overcome by increase concentration of substrate
competitive inhibitor
this type of inhibitor binds to the active site
competitive inhibitor
competitive inhibitors have this effect on Vmax
no effect
non0competitive inhibitors have this effect on Vmax
decreased
competitive inhibitors have this effect on Km
increased
Noncompetitive inhibitors have this effect on Km
no effect
enzyme regulation methods:
alter this for increased or decreased synthesis or destricution effects
enzyme concentrations
enzyme regulation methods: phosphorylation effects
covalent modification
enzyme regulation methods:
proteolytic modification effects
zymogen
enzyme regulation methods:
allosteric regulation effects
feedback inhibition
enzyme regulation methods:
steroid hormones effects
transcriptional regulation
Give the Cell cycle synthesis phases and what they stand for
M (mitosis: prophase-metaphase-anaphase-telophase)
G1 (growth)
S (synthesis of DNA)
G2 (growth)
Go (quiescent G1 phase)
these 2 phases are of variable duration
G1 & Go
this is usually the shortest phase
M
Most cells are in this phase
Go
rapidly dividing cells have a shorter ____ phase
G1
image- cell cycle phases p. 82
--
this is the site of synthesis of secretory (exported proteins and of N-linked oligosaccharide addition to many proteins
Rough endoplasmic reticulum (RER)
Mucus-secreting goblet cells of the small intestine and antibody-secreting plasma cells are rich here
RER
this is the site of steroid synthesis and detoxification of drugs and poisons
smooth endoplasmic reticulum (SER)
Liver hepatocytes and steroid hormone-producing cells of the adrenal cortex are rich in _____
SER
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 on asparagine
3) Adds O-oligosaccharides to serine and threonine residues
4) Proteoglycan assembly from proteoglycan core proteins
5) Sulfation of sugars in proteoglycans and of selected tyrosine on proteins
6) Addition of mannose-6 phosphate to specific lysosomal proteins, which targets the protein to the lysosome.
I cell disease is caused by the failure of the addition of _________ to lysosome proteins, causing thse enzymes to be secreted outside the cell inside of being targeted to the lysosome. Characterized by coarse facial features and restricted joint movement.
mannose-6-phosphate
This is a cylindrical sx 24 nm in diameter and of variable lenght. A helical array of polymerized dimers of alpha and Beta tubulin (13 per circumference). Each dimer has 2 GTP bound. Incorporated into flagella, cilia, mitotic spindles. Grows slowly, collapses quickly.
microtubules
this cell sxs are involved in slow axoplasmic transport in neurons
microtubules
name 5 drugs that act on microtubules
1) mebendazole/thiabendazole (antihelminthic)
2) taxol (anti Br CA
3) Griseofulvin (antifungal)
4) Vincristine/Vinblastine (anti-cancer)
5) Colchicine (anti gout
This syndrome is due to a microtubule polymerization defect resulting in decreased phagocytosis
Chediak-Higashi syndrome
this cell sx has 9 + 2 arrangement of microtubules
cilia
In cilia, this is an ATPase that links peripheral 9 doublets and causes bending of cilium by differential sliding of doublets
dynein
this syndrome is due to a dynein arm defect, resulting in immotile cilia
Kartagener's syndrome
dynein is
retrograde
kinesin is
anterograde
what are the 2 major components of plasma membranes
cholesterol (-50%)
phospholipids (-50%)

there are also sphingolipids, glycolipids, and proteins.
High cholesterol or long saturated fatty acid content results in this
increase melting temp.
this side of the membrane contains glycosylated lipids or proteins
noncytoplasmic side
T or F. The plasma membrane is an asymmetric, fluid bilater
T
This is a major component of RBC membranes, of myelin, of bile, and of surfactant. It is also used in the esterification of cholesteral.
Phosphatidylcholine
specific phosphatidylcholine used in esterification of chelesterol
LCAT is lecithin-cholesterol acyltransferase
specific phosphatidylcholine used in surfactant
DPPC= dipalmitoyl phosphatidylcholine
This is located in the plasma membrane w/ ATP site on the cytoplasmic side.
Na+K+ATPase (sodium pump)
For each ATP consumed, ___ Na+ go out and __ K+ come in.
3/2
During each cycle of the sodium pump this occurs
phosphorylation
This inhibits by blinding to K+ site.
Ouabain
These also inhibit the Na+K+ATPase causing increased cardiac contractility
cardiac glycosides (digoxin, digitoxin)
image sodium pump (p. 84)
--
G protein linked 2nd messengers [image p. 85]
--
This is the most abundant protein in the human body. It fxs to organize and strengthen extracellular matrix.
collagen
this type of collagen is 90% of collagen. It makes up BONE, tendon, skin, dentin, fascia, cornia, late wound repair
Type I

mneu: B Cool, Read Books
type I: bONE
this type of collagen makes up CARTILAGE (including hyaline), vitreous body, nucleus pulposis
Type II

mneu: B Cool, Read Books
type II: carTWOlage
this type of collagen makes up skin, blood vessels, uterus, fetal tissue, granulation tissue
Type III (reticulin)

mneu: B Cool, Read Books
this type of collagen makes up basement membrane or basal lamina
Type IV

mneu: B Cool, Read Books
Type IV: under the floor (basement membrane
This type of cartilage makes up the epiphyseal plate
Type X
collagen alpha chains are called
preprocollagen
preprocollagen is translated on this
RER
Inside fibroblast, collagen alpha chains or (preprocollagen) is usually this type of polypeptide
Gly-XY (X & Y are proline, hydroxyproline or hydroxylysine)
inside the the ER in fibroblasts hydroxylation of specific proline and lysine residues occurs. Hydroxylation requires this vitamen
C
Inside fibroblasts the golgi glycosylates the pro alpha chain lysine residues and formation of _______
procollagen (triple helix of 3 collagen chains)
these molecules are then exocytosed into into the extracellular space
procollagen
outside fibroblasts, procollagen peptidases cleave terminal regions of procollagen, transforming procollagen into insoluble ______
tropocollagen
Many staggered tropocollagen molecules are reinforced by covalent lysine-hydroxylysine cross linkage (by lysyl oxidase) to make
collagen fibrils
this syndrome results in faulty collagen synthesis causing:
1) hyperextensible skin
2) tendency to bleed (easy bruising)
3) hypermobile joints
ehlers-danlos syndrome
Ehlers-Danlos syndrome is associated with this problem
berry aneurysms
This dz is a primarily autosomal-dominant d/o caused by a variety of gene defects resulting in abnormal collagen synthesis. It is characterized by :
1) multiple fractures occuring with minimal trauma (brittle bone dz), which may occur during the birth process
2) Blue sclerae due to the translucency of the connective tissue over the choroid
3) hearing loss (abnormal middle ear bones)
4) Dental imperfections due to lack of dentition
osteogenesis imperfecta
What can osteogenesis be confused with
child abuse
what is the incidence of OI type I
1:10,000
what is the incidence of OI type II
0 - death in utero
Given the immunohistochemical stain give the cell type it stains for:
Vimentin
Connective tissue
Given the immunohistochemical stain give the cell type it stains for:
Desmin
muscle
Given the immunohistochemical stain give the cell type it stains for:
Cytokeratin
epithelial cells
Glial fibrillary acid proteins (GFAP)
neuroglia
Neurofilaments
neurons
Give the site of metabolism: Fatty acid oxidation (B-oxidation)
mitochondria
Give the site of metabolism: acetyl-CoA production
mitochondria
Give the site of metabolism: Krebs cycle
mitochondria
Give the site of metabolism: glycolysis
cytoplasm
Give the site of metabolism: fatty acid synthesis
cytoplasm
Give the site of metabolism: HMP shunt
cytoplasm
Give the site of metabolism: protein synthesis (RER)
cytoplasm
Give the site of metabolism: steroid synthesis (SER)
cytoplasm
Give the site of metabolism: gluconeogenesis
both cytoplasm and mitochondria
Give the site of metabolism: urea cycle
both cytoplasm and mitochondria
Give the site of metabolism: heme synthesis
both cytoplasm and mitochondria
summary of pathways [p.87]
--
give the enzyme deficiency that would result in MILD galactosemia
galactokinase
give the enzyme deficiency that would result in SEVERE galactosemia
galactose-1-phosphate uridyltransferase
give the enzyme deficiency that would result in Von Gierke's
glucose-6-phosphatase
give the enzyme deficiency that would result in essential fructosuria
fructokinase
give the enzyme deficiency that would result in fructose intolerance
aldolase B
This is an adenine base + ribose + 3 phosphoryls. 2 phosphoanhydride bonds, 7 kcal/mol each
ATP
aerobic metabolism of glucose produces this manny ATP via the malate shuttle and this many ATP via G3P shuttle
38
36
Anaerobic glycolysis produces this many ATP per glucose molecule
2
How is ATP hydrolysis used
it is coupled to energetically unfavorable rxns
ATP image p [88]
--
Give the activated carrier for each molecule:
ATP
phosphoryl
Give the activated carrier for each molecule: NADH, NADPH, FADH2
electrons
Give the activated carrier for each molecule: Coenzyme A, lipoamide
Acyl
Give the activated carrier for each molecule: biotin
CO2
Give the activated carrier for each molecule: tetrahydrofolates
1-carbon units
Give the activated carrier for each molecule: SAM
CH3 groups
Give the activated carrier for each molecule: TPP
Aldehydes
Give the activated carrier for each molecule: UDP-glucose
Glucose
Give the activated carrier for each molecule: CDP-choline
Choline
ATP + methionine -->
SAM
What does SAM do?
SAM transfers methyl units to a wide variety of acceptors (e.g., synthesis of phosphocreatine, a high-energy phosphate active in muscle ATP production).

mneu: SAM the methyl donor man
Regeneration of methionine (and thus SAM) is dependent on this vitamen
B12
give the signal molecule given its precursor: ATP ->
cAMP via adenylate cyclase
give the signal molecule given its precursor: GTP ->
cGMP via guanylate cyclase
give the signal molecule given its precursor: Glutamate ->
GABA via glutamate decarboxylase (requires vitamen B6
give the signal molecule given its precursor: choline->
ACH via choline acetyltransferase (ChAT)
give the signal molecule given its precursor: arachidonate->
prostaglandins, thromboxanes, leukotrienes via cyclooxygenase/ lipoxygenase
give the signal molecule given its precursor: fructose-6-P->
fructose 1,6-bis-P via phosphofructokinase (PFK), the rate-limiting enzyme of glycolysis
give the signal molecule given its precursor: 1,3BPG->
2,3-BPG via bisphosphoglycerate mutase
what are the 2 universal electron acceptors
Nicotinamides (NAD+,NADP+) and flavin nucleotides (FAD+)
NADPH is a procatabolicduct of this pathway
HMP shunt
NAD+ is generally used in _______ processes to carry reducing equivalents away as NADH
catabolic
NADPH is used in _____ processes (steroid and fatty acid synthesis) as a supply of reducing equivalents
anabolic
NADPH is used in these 3 ways:
1) anabolic processes
2) respiratory burst
3) P-450
image p. 89 -oxygen dependent respiratory burst
--
where is hexokinase found
throughout the body
where is glucokinase found
liver

mneu: gLucokinase in Liver
describe the Km and Vmax of glucokinase in comparison to hexokinase
glucokinase has a lower affinity [higer Km] but higher capacity [ higher Vmax]
which one hexokinase or glucokinase is feedback inhibited by G6P
hexokinase
which one hexokinase or glucokinase phosphorylates excess glucose (e.g., after a meal) to sequester it in the liver as G6P
glucokinase
give the irreversible enzymes in glycolysis regulation
hexokinase/glucokinase
phosphofructokinase-1 (RLS)
pyrovate kinase
pyruvate dehydroginase
hexokinase/glucokinase converts D-glucose into what?
what is this inhibited by?
Glucose-6-P
Glucose-6-P(inh by product)
phosphofructokinase-1 (RLS) converts fructose 6-phosphate into what?
what is it inhibited by?
stimulated by?
Fructose-1,6-BP
inh by: ATP, citrate
stim by: AMP,Fructose-2,6-BP
pyrovate kinase converts phosphoenolpyruvate into what?
what is it inhibited by?
stimulated by?
pyruvate
stim: fructose-1,6-BP
inh: ATP, alanine
pyruvate dehydroginase converts pyuvate into what?
what is it inhibited by?
Acetyl CoA
inh: ATP, NADH
Acetyl-CoA
Glycolyc enzyme deficiencies such as hexokinase, glucose phosphate isomerase, aldolase, triosephosphate isomerase, phosphate glycerate kinase, enolase, and pyruvate kinase deficiencies are associated with what condition
hemolytic anemia
why do glycolytic enzyme deficiencies result in hemolytic anemia
RBCs metabolize glucose anaerobically (no mitochondria) and thus depend solely on glycolysis
The pyruvate dehydrogenase complex contains 3 enzymes that require 5 cofactors. What are these cofactors.
1) pyrophosphate (B1, thyamine; TTP)
2) FAD (B2, riboflavin)
3) NAD (B3, niacin)
4) CoA (B5, pantothenate)
5. Lipoic acid
Pyruvate dehydrogenase complex is similar to what other complex (same cofactors, similar substrate and action)
alpha ketoglutarate
give thee pyruvate dehydrogenate reaction.
pyruvate + NAD+ + CoA
-> acetyl CoA + CO2 + NADH
pyruvate dehydrogenase complex is activated by exercise because it increases these three things
NAD+/NADH ratio
ADP
Ca++
pyruvate dehydrogenase deficiency causes a backup of substrate which is?
pyruvate and alanine
pyruvate dehydrogenase deficiency results in this
lactic acidosis
pyruvate dehydrogenase deficiency is often seen in alcoholics due to a deficiency of this vitamen
B1
someone with a pyruvate dehydrogenase deficiency may present with this deficit
neurologic
what is the tx for pyruvate dehydrogenase deficiency
increase intake of ketogenic nutrients (e.g., high fat content or high lysine and leucine)
name the only purely ketogenic amino acids
lysine and leucine
image p. 90 pyruvate metabolism
--
how many ATP equivalents are needed to generate glucose from pyruvate
6
this AA serves as a carrier of amino groups form mm to liver
alanine
this can be used to replenish TCA cycle or in gluconeogenesis
oxaloacetate
This cycle transfers excess reducing equivalents from RBCs and mm to liver, allowing muscle to funcction anaerobically (net 2 ATP)
cori cycle
TCA cycle enzymes
Citrate
Isocitrate
alpha-Ketogluterate
Succinyl-CoA
Succinate
Fumarate
Malate
Oxaloacetate

mneu: Can I Keep Selling Sex For Money, Officer?
What does the TCA cycle produce per Acetyl-CoA?
how much do we multiply these numbers by if we are dealing with glucose?
3NADH,
1FADH2
2CO2
1GTP
12 ATP

2x w/ glucose
image TCA cycle p. 91
--
in the electron transport cha in 1 NADH gives how many ATP
3
in the electron transport cha in 1 FADH gives how many ATP
2
name 4 electron transport inhibitors that directly inhibit electron transport, causing a decrease of proton gradient and block ATP synthesis
rotenone, antimycin A, CN-, CO
This ATPase inhibitor directly inhibits mitochondrial ATPase, causing an increase of proton gradient, but no ATP is produceed because electron transport stops
oligomycin
Uncoupling agents like this increase the permeability of the membrane, causing a decrease of proton gradient and increase O2 consumption. ATP synthesis stops. Electron transport continues.
2,4 DNP
irreversible enzymes in gluconeogenesis
pyruvate carboxylase
PEP carboxykinase
Fructose-1,6-biphosphatase
Glucose-6-phosphate

mneu: Pathway Produces Fresh Glucose
pyruvate carboxylase is found here and converts this to this
It requires this
& is activated by this
mitochondria
pyruvate ->oxaloacetate
biotin, ATP
Acetyl-CoA
PEP carboxykinase is found here and converts this to this
It requires this
cytosol
oxaloacetate
->phosphoenolpyruvate
GTP
Fructose-1,6-biphosphatase is found here and converts this to this.
cytosol
fructose-1,6 bisphosphate
->fructose-6-P
where does gluconeogenesis occur
liver, kidney, intestinal epithelium

note: mm cannot participate in gluconeogenesis
deficiency of key gluconeogenic enzymes results in this
hypoglycemia
this dz is caused by a lack of glucose 6 phospatase in the liver
Von Gierke's
This pathway produces ribose-5-P for nucleotide synthesis
and produces NADPH from NADP+ for fatty acid and steroid biosynthesis and for maintaining reduced glutathione inside RBCs
Pentose Phosphate Pathway (HMP shunt)
All pentose Phosphate Pathway (HMP shunt) reactions occur here
cytoplasm
Is ATP used or produced in Pentose Phosphate Pathway (HMP shunt)
no
give sites of Pentose Phosphate Pathway (HMP shunt)
all sites of fatty acid or steroid synthesis (e.g., lactating mammary glands, liver, adrenal cortex
this is the rate-limiting enzyme in HMP shunt (which yields NADPH)
G6PD
NADPH is necessary to keep this reduced, which in turn detoxifies free radicals and peroxides
glutathione
decreased NADPH in RBCs lead to this due to poor RBC defense against oxidizing agents (fava beans, sulfonamides, primaquine) and antituberculosis drugs
hemolytic anemia
G6PD deficiency is more prevelent amun this racial group
blacks
this sign of G6PD deficiency describes when hemoglobin precipitates within RBCs
Heinz bodies
G6PD deficiency has this inheritance
x-linked recessive
image p. 92 - G6PD deficiency
--
This is a hereditary deficiency of aldolase B (recessive) Fructose-1-phosphate accumulates causing a decrease in available phosphate, which results in inhibition of glycogenolysis and gluconeogenesis.
Symptoms include hypoglycemia,jaundice, cirrhosis, vomiting
fructose intolerance
what is the tx for fructose intolerance
decrease intake of both fructose and sucrose (glucose + fructose)
this d/o involves a defect in fructokinases and is a benign, asymptomatic condition.
Symptoms: fructose appears in blood and urine.
essential fructosuria
essential fructosuria is a deficiency in this enzyme
fructokinase
fructose intolerance is a deficiency in this enzyme
aldolase B
This d/o is an absense of galactose-1-phosphate uridyltransferase. It is autosomal recessive. Damage is caused by accumulation of toxic substances (including galactitol) rather than absense of an essential compound.
Symptoms: cataracts, hepatosplenomegaly, mental retardation
galactosemia
tx of galactosemia
exclude galactose and lactose (galactose + glucose) from diet
this enzyme deficiency causes galactosemia and galactosuria, galactosuria, galactitol accumulation if galactose is present in ddiet.
galactokinase deficiency
image p. 93 galactose metabolism
--
this is an age dependent or hereditary intolerance to dairy often seen in blacks and asians. Symptoms include bloating, cramps and osmotic diarrhea.
Tx includes avoiding milk or adding lactase pills to diet
lactase deficiency
give the ketogenic essential amino acids
leucine, lysine

All essential amino acids: PriVaTe TIM HALL
give the glucogenic/ketogenic essential amino acids
Ile, Phe, Trp

All essential amino acids: PriVaTe TIM HALL
give the glucogenic essential amino acids
Met, Thr,Val, Arg, His

All essential amino acids: PriVaTe TIM HALL
which 2 AA are required during periods of growth
Arg
His
what are the acidic amino acids
Asp, Glu

mneu: Asp=aspartic ACID, Glu=glutamic ACID
At body pH (7.4) acidic amino acids (Asp, Glu)are _____ charged
negatively
what are the basic amino acids
arg, lys, his
At body pH (7.4) basic amino acids (Arg, lys)are _____ charged, but _____ has no net charge
positively

his
arg and lys have an extra _____ group
NH3
the MOST basic amino acid
arginine
thise 2 AA are found in high amounds in histones, which bind to negatively charged DNA
arg, lys
image p 94. Transport of ammonium by alanine and glutamine
--
this cycle degrades amino acids into amino groups. It accounts for 90% of the nitrogen in the urine.
urea cycle
urea cycle occurs in this organ
liver
in what part of the cell does the urea cycle occur
carbamoyl phosphate incorporation occurs in the mitochondria; the remaining steps occur in the cytosol
urea cycle image p. 94
ornithine, Carbamoyl phosphate, Citrulline, Aspartate, Argininosuccinate, Fumarate, Arginine, urea

mneu: Ordinarily, Careless Crappers Are Also Frivolous About Urination
give the amino acid derivative of epinephrin
phenylalanine
give the amino acid derivative of thyroxine
phenylalanine
give the amino acid derivitive of NAD+/NADP+
tryptophan
give the amino acid derivative of melanin
phenylalanine
give the amino acid derivative of serotonin
tryptophan
give the amino acid derivative of melatonin
tryptophan
give the amino acid derivative of histamine
histadine
give the amino acid derivative of heme
Glycine
give the amino acid derivative of creatine
arginine
give the amino acid derivative of urea
arginine
give the amino acid derivative of nitric oxide
arginine
give the amino acid derivative of GABA
glutamate
give the amino acid derivative of dopamine
phenylalanine
give the amino acid derivative of norepinephnine
phenylalanine
In normal metabolism phenylalanine is converted into _____
tyrosine
in PKU there is decreased ________ or decreased tetrahydrobiopterin cofactor
phenylalanine hydroxylase
findings of phenylketonuria
mental retardation, growth retardation, fair skin, eczema, musty body odor.

mneu: d/o of AROMATIC amino acid metabolism -> musty body ODOR
tx of PKU
no phenylalanine in diet (e.g., aspartame, nutrasweet) and increase in tyrosine
when should you screen for PKU
at birth
name the 3 phenylketones
phenylacetate
phenyllactate
phenylpyruvate
what is the inheratiance of PKU & incidence
autosomal-recessive dz
1:10,000
this is a congenital deficiency of homogentisic acid oxidase in the degradative pathway of tyrosine.
alkaptonuria
in alkaptonuria, these cause the urine to turn black on standing
alkapton bodies
in alkaptonuria, in addition to dark urine this is also dark
connective tissue
pts w/ alkaptonuria may have debilitating
arthralgias
this d/o is a congenital deficiency of either of the follwoing:
1) tyrosinase (inability to synthesize melanin from tyrosine)
2) Defective tyrosine transporters (decrease amounts of tyrosine and thus melanin)
It can result from lack of migration of neural crest cells
albinism
lack of melanine results in an increase risk of this CA
skin CA
this dz results in excess homocysteine in the urine. Cysteine becomes essential. It can cause mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation (downward and inward) and atherosclerosis (stroke and MI
homocystinuria
there are three forms of homocystinuria. Name the enzyme deficiency and give the dietary txs if there is one
1) cytathionine synthase deficiency (tx: decrease Met & increase Cys in diet)
2) decrease affinity of cystathionine synthase for pyridoxal phosphate (tx: increase vit. B6 in diet)
3) Methionine synthase deficiency
image. Homocystinuria. p.96
--
This is a common(1:7000) inherited defect of renal tubular amino acid transporter for Cystine, Ornithine, Lysine, and Arginine in kidneys. Excess cystine in urine can lead to the precipitation of cystine kidney stones
Cystinuria

mneu: COLA in the urine
this is a congenital deficiency of homogentisic acid oxidase in the degradative pathway of tyrosine.
alkaptonuria
in alkaptonuria, these cause the urine to turn black on standing
alkapton bodies
in alkaptonuria, in addition to dark urine this is also dark
connective tissue
pts w/ alkaptonuria may have debilitating
arthralgias
this d/o is a congenital deficiency of either of the follwoing:
1) tyrosinase (inability to synthesize melanin from tyrosine)
2) Defective tyrosine transporters (decrease amounts of tyrosine and thus melanin)
It can result from lack of migration of neural crest cells
albinism
tx for Cystinuria
acetazolamide to alkalinize the urine
this dz results from blocked degradation of BRANCHED AA (Ile, Val, Leu) due to decreease alpha ketoacid dehydrogenase. It causes increased alpha ketoacids in the blood, esp Leu. It causes severe CNS defects, mental retardation, and death.
maple syrup urine dz

mneu: urine smells like maple syrup. I Love Vermont maple syrup
tx for Cystinuria
acetazolamide to alkalinize the urine
this dz results from blocked degradation of BRANCHED AA (Ile, Val, Leu) due to decreease alpha ketoacid dehydrogenase. It causes increased alpha ketoacids in the blood, esp Leu. It causes severe CNS defects, mental retardation, and death.
maple syrup urine dz

mneu: urine smells like maple syrup. I Love Vermont maple syrup
purine salvage deficiencies p. 97
--
what does SCID stand for?
What is the enzyme deficiency?What immune cells are involved?
Who does it effect
Severe combined (T and B) immuodeficiency dz.
Adenosine deaminase (ADA)deficiency
happens to kids

mneu: bubble boy
pathophysiology of SCID
excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase. This prevents DNA synthesis and thus decreases lymphocyte count.
This dz results from a purine salvage problem owing to absense of HGPRTase, which vonverts hypoxanthine, to inosine monophosphate (IMP) and guanine to guanosine monophosphate (GMP)
Lesch-Nyyhan syndrome

mneu: LNS- Lacks Nucleotide Salvage (purine)
inheratance of Lesch Nyhan syndrome
X-linked recessive.
LNS results in excess of this acid
uric acid
patient manifestation of Lesch-Nyhan syndrome
retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis
image fed state v. fasting state p. 97
--
is the fasting state phosphorylated or non-phosphorylated
phosphorylated

mneu: in the fasting state phosphorylate
this hormone is required for adipose and skeletal mm uptake of glucose
insulin

mneu: INsulin moves glucose INto cells
where is insulin made (cells/organ)
Beta cells of pancreas
what receptors are found in the beta cells
GLUT 2
what receptors are found in mm and fat
GLUT 4
insulin inhibits the release of this hormone by alpha cells of pancreas
glucagon
is serum C-peptide present w/ exogenous insulin intake
no
what are the anabolic effects of insulin
1) glucose transport
2) glycogen synthesis and storage
3) triglyceride synthesis and storage
4)Na+ retention (kidneys)
5) protein sytnesis (mm
Name the tissues that don't need insulin for glucose uptake
Brain
RBCs
Intestine
Cornea
Kidney
Liver

mneu: BRICK L
Glucagon ______ (phosphorylates/Dephosphorylates), turns glycogen sytnase _____ and phosphorylase ____
phosphorylates
OFF
ON
Insulin______ (phosphorylates/Dephosphorylates), turns glycogen sytnase _____ and phosphorylase ____
dephosphorylates
ON
OFF
there are 12 types of these diseases all resulting in abnormal glycogen metabolism and accumulation of glycogen within cells
glycogen storage diseases
In this glycogen storage disease, there is a glucose 6-phosphatase deficiency
Von Gierke's dz (GSD type I)
Give some clinical findings of Von Gierke's dz (GSD type I)
severe fasting hypoglycemia, increased glycogen in the liver, hepatomegly, increased blood lactate

hint: the liver becomes a mm
In this glycogen storage disease, there is a lysosomal alpha 1,4-glucosidase deficiency
Pompe's dz (type II)
Give some findings of Pompe's dz
cardiomegly and systemic findings, leading to early death

mneu: Pompe's trashes the Pump
(heart, liver mm)
In this glycogen storage disease, there is a deficiency of debranching enzyme alpha 1,6 glucosidase
Cori's dz (type III)
give some clinical findings of Cori's dz
milder form of type I w/ normal blood lactate levels
In this glycogen storage disease, there is a deficiency of skeletal mm glycogen phosphorylase deficiency
McArdle's dz (type V)

mneu: McArdle's: Muscle
Give some findings of McArdle's dz
increased glycogen in mm but cannot greak it down, leading to painful cramps, myoglobinuria w/ strenuous exercise
this classification of dz is caused by a deficiency in one of the many lysosomal enzymes
lysosomal storage diseases
clinical findings are peripheral neuropahty of hands/feet, antiokeratomas, CV/renal dz. What is the dz? deficient lysosomal enzyme? Accumulated substrate? Inheritance?
Fabry's dz
alpha-galactosidase A
Ceramide trihexoside
XR
clinical findings are hepatosplenomegly, aseptic necrosis of femur, bone crises. What is the dz? deficient lysosomal enzyme? Accumulated substrate? Inheritance?
Gaucher's dz
B-glucocerbrosidase
Glucocerebroside
AR
clinical findings are progressive neurodegeneration, HSM, cherry red spot on macula What is the dz? deficient lysosomal enzyme? Accumulated substrate? Inheritance?
Niemann-Pick dz
Sphingomyelinase
Sphingomyelin
AR

mneu:NO MAN PICS (NIEMANN-PICK) his nose w/ his SPHINGER(SPHINGomylenase
clinical findings are progressive neurodegeneration, developmental delay, cherry-red spot, lysozymes w/ onion skin. What is the dz? deficient lysosomal enzyme? Accumulated substrate? Inheritance?
Tay-Sachs dz
Hexosaminidase A
GM2 ganglioside
AR

mneu: Tay-SaX (Tay-Sachs) lacks heXosaminidase
clinical findings are peripheral neuropathy, developmental delay, optic atrophy. What is the dz? deficient lysosomal enzyme? Accumulated substrate? Inheritance?
Krabbe's dz
B-galactosidase
Galactocerebroside
AR
clinical findings are central and peripheral demyelination w/ ataxia, dementia. What is the dz? deficient lysosomal enzyme? Accumulated substrate? Inheritance?
Metachromatic leukodystophy
Arylsulfatase A
Cerebroside sulfate
AR
clinical findings are developmental delay, gargoylism, airway obsxn, corneal clouding, HSM What is the dz? deficient lysosomal enzyme? Accumulated substrate? Inheritance?
Hurler's syndrome
alpha-L-iduronidase
Heparan sulfate & dermatan sufate
AR
clinical findings are mild Hurler's w/ aggressive behavior, no corneal clouding. What is the dz? deficient lysosomal enzyme? Accumulated substrate? Inheritance?
Hunter's syndrome
Iduronate sulfatase
heparan sulfate, dermatan sulfate
XR

mneu: HUNTERS aim for the X (X-linked recessive)
fatty acid metabolism. image 100
--
Where does fatty acid degradation occur
mitochondria
(where its products will be consumed)
in the liver, fatty acid and amino acids are broken down into ______ to be used by _____ & ______
ketone bodies (acetoacetate + hydroxybuterate
To be used in mm & brain).
when are ketone bodies found
prolonged starvation and diabetic ketoacidosis
how are ketone bodies excreted
urine
what are ketone bodies made from
HMG CoA
Ketone bodies are metabolized by the brain to 2 molecules of _______
acetyl-CoA
how do ketone bodies smell on the breath
like acetone (fruity odor)
What is the rate-limiting step in cholesterol synthesis
HMG-CoA reductase, which converts HMG-CoA to mevalonate.
What cholesterol drug inhibits HMG CoA reductase
Lovastatin
2/3 of plasma cholesterol is esterified by this
lecithin-cholesterol acyltransferase (LCAT)
image lipoproteins p. 101
--
this lipase is responsible for degradation of dietary TG in the small intestine
pancreatic lipase
this lipase is responsible for degradation TG circulating in chylomicrons and VLDLs
lipoprotein lipase
this lipase is responsible for degradation TG remaining in IDL
Hepatic TG lipase
this lipase is responsible for degradation of TG stored in adipocytes
hormone sensitive lipase
this major apolipoprotein Activates LCAT
AI
this major apolipoprotein Binds to LDL receptor
B-100
this major apolipoprotein is a Cofactor for lipoprotein lipase
CII
this major apolipoprotein mediates Extra (remnant) uptake
E
the cells in this part of the body convert FFA back to TG and package it in chylomicrons
intestines
give the 5 lipoproteins
chylomicrons, VLDL, IDL, LDL, HDL
this lipoprotein delivers dietary triglycerides to peripheral tissues and dietary cholesterol to the liver. It is secreted by intestinal epithelial cells. Excess causes pancreatitis, lipemia retinalis, and eruptive xanthomas
chylomicron
Apolipoprotein ____ mediates secetion of chylomicrons
B-48
Apolipoprotein ____ are used for formation of new HDL
A
Apolipoprotein ____ activates lipoprotein lipase
C-II
Apolipoprotein ____ mediates remnant uptake by liver
E
These lipoproteins deliver hepatic triglycerides to peripheral tissues.
VLDL
VLDL is secreted by this organ
liver
excess VLDL causes this dz
pancriatitis
this apolipoprotein mediates secretion of VLDL
B-100
this apolipoprotein mediates remnant uptake of VLDL by the liver
E
this lipoprotein is formed in the degradation of VLDL. It delivers triglycerides and cholesterol to the liver, where they are degraded to LDL
IDL
This lipoprotein delivers hepatic cholesterol to peripheral tissues It is formed by a lipoprotein lipase modification of VLDL in the peripheral tissue. It is taken up by target cells via receptor-mediated endocytosis. Excess causes atherosclerosis, xanthomas, and arcus cornae
LDL
this LDL apolipoprotein mediates binding to cell surface receptor for endocytosis
B-100
This lipoprotein mediates centripetal transport of cholesterol (reverse cholesterol transport, from perhiphery to liver). It acts as a repository for apoC and apo E (which are needed for chylomicron and VLDL metabolism). It is secreted from both liver and intestine
HDL
this HDL apolipoprotein helps form HDL sx
A
this HDL apolipoprotein in particular activates LCAT (which catalyzes esterification of cholesterol)
A-I
this HDL apolipoprotein mediates transfer of cholesterol esters to other lipoprotein particles.
CETP
LDL & HDL carry most cholesterol. ___ transports cholesterol from liver to tissue; ____ transports it from periphery to liver
LDL
HDL
This type of familial dyslipidemia results from a lipoprotein lipase deficiency or altered apolipoprotein CII. It results in increased chylomicrons which leads to elevated blood levels of TG & cholesterol
type I - hyperchylomicronemia
This type of familial dyslipidemia results from a decrease in LDL receptors. It results in an increase of LDL which leads to elevated cholesterol.
type IIa hypercholesterolemia
This type of familial dyslipidemia results from a hepatic overproduction of VLDL leading to an increase in LDL and VLDL leading to elevated TG & cholesterol
type IIb-combined hyperlipidemia
This type of familial dyslipidemia results from altered apolipoprotein E leading to an increase in IDL & VLDL resulting in elevated TG & cholesterol
type III-dysbetalipoproteinemia
This type of familial dyslipidemia results from hepatic overproduction of VLDL resulting in increased VLDL levels leading to elevated TGs in the blood
type IV-hypertriglyceridemia
This type of familial dyslipidemia results from increased production and decreased clearance of VLDL and chylomicrons leading to increased VLDL and chylomicrons resulting in elevated blood levels of TGs & cholesterol
type V-mixed hypertriglyceridemia
underproduction of heme causes this type of anemia
microcytic hypochromic
accumulations of heme intermediates causes thius
porphyrias
image p103- heme synthesis
---
this type of porphyria inhibits ferrochelatase and ALA dehydrase. Cooproporphyrin and ALA accumulate in the urine
lead poisoning
this type of porphyria results from a deficiency in uroporphyrinogen I synthetase. Porphobilogen and delta-ALA accumulate in urine
Acute intermittent porphyria
this type of porphyria results from a deficiency in uropophyrinogen decarboxylase. Uroporphyrin accumulates in urine (tea-colored). results in photosensitivity
Porphyria cutanea tardia
symptoms of porphyrias (5 Ps)
Painful abdomen
Pink urine
Polyneuropathy
Psychological disturbances
Precipitated by drugs
heme is scavenged from RBCs and ____ is reused
Fe++
heme ->_____->bilirubin
biliverdin
bilirubin is toxic to this organ system
CNS
bili is transported by this protein
albumin
bili is removed from the blood by this organ
liver
bili is conjugated with this ____
glucuronate
bili is excreted in this supstance
bile
where in the body is bili processed into its excreted form
intestine
some ________, an intestinal intermediate, is reabsorbed into blood and excreted as urobilin into urin
urobilinogen
this poison has a 200x greater affinity than O2 for HGB
CO
hemoglobin is composed of 4 polypeptide subunits. describe them
2 alpha
2 beta
HGB exists in 2 forms what are they
T (taut) low affinity for O2
R (relaxed) high affinity for O2 (300x)
Hgb exibits _______ cooperativity and ________ allostery (accounts for the sigmoid-shaped O2 dissociation curve for hgb), unlike myoglobin
positive
negative
name the things that favor the relaxed form of hgb (shifting dissociation curve to the right, leading to O2 unloading)
increased Cl-,H+,CO2,2,3BPG, hight temp.

mneu: when you're relaxed, you do your job better (carry O2)
what are the fetal hgb subunits
2alpha
2gamma
fetal hgb has a lower affinity for _____ than adult hgb and thus has a higher affinity for O2
2,3-BPG
Iron in hgb is in a _____ state (ferrous, Fe++)
reduced
this is an oxidized form of hgb (ferric, Fe++) that does not bind O2 as readily but has increased affinity for CN-.
methemoglobin
administer this in cyanide poisoning to oxidize hgb to methemoglobin form
nitrites
tx toxic levels of METHemoglobin with -----
METHylene blue
CO2 is transported in the blood by binding to
amino acids in the globin chain (at N terminus) but not to heme
CO2 binding favors this form of hgb (and thus promotes O2 unloading)
taut
CO2 must be transported from tissue to lungs, the reverse of O2, and this occurs primarily in what form
bicarbinate
this is a molecular biology laboratory procedure that is used to synthesize many copies of a desired fragment of DNA
polymerase chain reaction (PCR
steps of PCR
1) DNA is denatured by heating to generate 2 separate strands
2)during cooling, excess premade DNA primers anneal to a specific sequence on each strand to be amplified
3) heat-stable DNA polymerase replicates the DNA sequence following each primer

These steps are repeated multiple times for DNA sequence aplification
In this molecular biology technique, a DNA sample is electrophoresed on a gel and then transferred to a filter. The filter is then soaked in a denaturant and subsequently exposed to a labeled DNA probe that recognizes and anneals to its complementary strand. The resulting double stranded labeled piece of DNA is visualized when the filter is exposed to film.
southern blot

SNoW DRoP:
Southern=DNA
Northern=RNA
Western=Protein
this molecular biology technique, is a similar technique, except that it involves radioactive DNA probe binding to sample RNA
northern blot

SNoW DRoP:
Southern=DNA
Northern=RNA
Western=Protein
In this molecular biology technique, sample protein is separated via gel electrophoresis and transferred to a filter. Labeled antibody is used to bind to relevant PROTEIN
Western drop

SNoW DRoP:
Southern=DNA
Northern=RNA
Western=Protein
in this method of testing, a pts blood sample is probed with either:
1)test Ag (coupled to color-generating enzyme)-to see if immune system recognizes it; or
2) Test Ab (coupled to color generating enzyme) to see if certain Ag is present

If the target subsance is present in the sample, the test solution will have an intense color reaction, indicating a positive test result.
Enzyme-linked immunosorbent assay (ELISA)
image ELISA p. 105
--
ELISA is used in many labs to determine whether a particular ___(e.g., anti-HIV) is present in a pts blood sample. Both the sensitivity and specificity of ELISA approach 100% but both false positive and false negative results do occur
Antibody
define the genetic term VARIABLE EXPRESSION
nature and severity of the phenotype varies from 1 individual to another
define the genetic term INCOMPLETE PENETRANCE
Not all individuals with a mutant genotype show the mutant phenotype
define the genetic term PLEIOTROPY
1 gene has >1 effect on an individual's phenotype
define the genetic term IMPRINTING
differences in phenotype depend on whether the mutationis of maternal or paternal origin (e.g., AngelMan's syndrome [Maternal], Prader-Willi syndrome [Paternal]
define the genetic term ANTICIPATION
Severity of dz worsens or age onset of dz is earlier in succeeding generations (e.g., Huntington's dz)
define the genetic term LOSS OF HETEROZYGOSITY
If a pt inherits or develops a mutation in a tumor suppressor gene, the complimentary allele must be deleted/mutated before CA develops. This is not true of oncogenes
define the genetic term DOMINANT NEGATIVE MUTATION
exerts a DOMINANT EFFECT. A heterozygote produces a nonfxnl altered protein that also prevents the normal gene product from funcioning
define the genetic term 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
define the genetic term MOSAICISM
occurs when cells in the body have different genetic makeup (e.g. lyonization--random X inactivation in females)
define the genetic term LOCUS HETEROGEITY
Mutations at different loci can produce the same phenotype (e.g., albinism
Hardy-Weinberg law assumes (4)
1) there is no mutation occurring at the locus
2) there is no selection for any of the genotypes at the locus
3) Mating is completely random
4) There is no migration into or out of the population
If a population is in Hardy-Weinberg equilibrium. p and q are separate allele. 2pq=heterozygote prevalence.

allele prevalence is?
disease prevalence is?
p+q=1
p2 + 2pq +q2 =1
this mode of inheritance looks like this [p.107]







Often due to defects in sxl genes. Many generations, both male and female, affected. It is often pleiotropic and, in many cases, present clinically after puberty. Family hx is crucial to dx
Autosomal dominant
this mode of inheritance looks like this [p.107]







25% of offspring from 2 carrier parents are affected. Often due to enzyme deficiencies. Usually seen in only 1 generation. Commonly more severe. Pts often present in childhood.
autosomal recessive
this mode of inheritance looks like this [p.107]







Sons of heterozygous mothers have a 50% chance of being affected. No male-to-male transmission. Commonly more severe in males. Heterozygous females may be effected.
X linked recessive
this mode of inheritance looks like this [p.107]







transmitted through both parents. Either male or female offspring of the affected mother may be affected, while ALL female offspring of the affected father are diseased. e.g., Hypophosphatemic rickets.
X linked dominant
this mode of inheritance looks like this [p.107]







transmitted only through mother. All offspring of affected females may show signs of dz. e.g., Leber's hereditary optic neuropathy.
mitochondrial inheritance
This autosomal dominant dz, is ALWAYS BILATERAL, there is a massive enlargement of kidneys due to multiple large cysts. Pts present with pain, hematuria, hyperension, progressive renal failure. 90% of cases are due to mutation in APKD1 (chromosome 16). Associated w/ polycystic liver dz, berry aneurysms, mitral valve prolapse. Juvenile form is recessive
Adult Polycystic Kidney Dz
This autosomal dominant dz, is characterized by elevated LDL owing to defective or absent LDL receptor. Heterozygotes (1:1500) have cholesterol~300mg/dl. Homozygotes (very raare) have cholesterol ~700+mg/dl, severe atherosclerotic dz early in life, and tendon xanthomas (classically in the Achilles tendon); MI may develop before age 20.
Familial hypercholesterolemia (hyperlipidemia type IIA)
This fibrillin gene mutation results in connective tissue disorders. It results in skeletal abnormalities--tall with long extremities (arachnodactylyl), hyperextensive joints, and long, tapering fingers and toes.
CV--cystic medial necrosis of aorta leading to aortic incompetence and dissecting aortic aneurysms. Floppy mitral valve.
Ocular-subluxation of lenses
Marfan's syndrome
This autosomal dominant dz, is characterized by cafe-au-lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas). Also marked by skeletal d/o (e.g., scoliosis), pheochromocytoma, and increased tumor suceptibility. On long arm of chromosome 17
Neurofibromatosis type 1 (von Recklinghausen's dz)

mneu: chrom 17-17 letters in von Recklinghausen
This autosomal dominant dz, is characterized by bilateral acoustic neuroma, optic pathway gliomas, juvenile cataracts.
Neurofibromatosis type 2
Neurofibromatosis type 2 is on this gene on this chromosome
NF2 gene on chrom 22
This autosomal dominant dz, is characterized by facial lesions (adenoma sebaceum), hypopigmented "ash leaf spots" on skin, cortical and retinal hamartomas, seizures, mental retardation, renal cysts, cardiac rhabdomyomas. Incomplete penetrance, variable presentration.
Tuberous sclerosis
This autosomal dominant dz, is characterized by hemangioblastomas of retina/cerebellum/medulla; about half of affected individuals develop multiple bilateral renal cell carcinomas and other tumors.
Von Hippel-Lindau dz
Von Hippel-Lindau dz is associated with deletion of this gene on this chromosome
VHL gene (tumor suppressor) on chromosome 3 (3p)

mneu: VHL=3 words=chrom 3
This autosomal dominant dz, is characterized by depression, progressive dementia, choreiform movements, caudate atrophy and decreased levels of GABA and ACH in the brain. Symptoms manifest in affected individuals between the ages of 20 and 20.
Huntington's dz
Huntington's dz gene is located on this chromosome. It is a _____ repeat d/o
chrom 4
triplet repeat

mneu: "Hunting 4 food"
This autosomal dominant dz, is characterized by the colon becoming covered with adenomatous polyps after puberty. Progresses to cancer unless resected.
familial adenomatous polyposis
familial adenomatous polyposis is a deletion of this chromosome
5

mneu: 5 letters in "polyp"
This autosomal dominant dz, is characterized by spheroid erythrocytes; hemolytic anemia; increased MCHC. Splenectomy is curative
hereditary spherocytosis
This autosomal dominant dz, is characterized by autosomal-dominant cell-signaling defect of fibroblast growth factor (FGF) receptor 3. Results in dwarfism; short limbs; but head and trunk are normal size
achondroplasia
name 5 autosomal-recessive dzs
CF, albinism, alpha1 antitrypsin deficiency, PKU, thalassemias, sickle cell anemia, glycogen storage dz, mucopolysaccharidosis (except Hunter's), sphingolipidosies (except Fabry's), infant polycystic kidney dz, hemochromatosis
CF has this inheratance
autosomal recessive
what is the gene and chromosome of CF
CFTR on chromosome 7
what is the defective channel in CF that results in secretion of abnormally thick mucus that plugs lungs, pancreas, and liver.
Cl-
the recurrent pulmonary infections in CF are often due to these 2 bugs
pseudomonas and S. aureus.
this CF complication results in malabsorption and steatorrhea
pancreatic insufficiency
CF can cause this in this in newborns
meconium ileus
how do you dx CF
incresed concentration of Cl-ions in a sweat test.
CF can cause this in males due to absent vas deference
infertility
these vitamen deficiencies can be present in CF. It may present as failure to thrive in infancy
ADEk
CF is the most common lethal genetic dz in this racial group
caucasians
in CF this tx will loosen mucous plugs
N-acetylcystein
Give 5 X-linked recessive disorders
fragile X, duchenne's muscular dystorphy, hemophilia A & B, Fabry's, G6PD deficiency, Hunter's syndrome, ocular albinism, Lesch-Nyhan syndrome, Bruton's agammaglobinemia, Wiskott-Aldrich syndrome
T or F. Female carriers of X-linked recessive d/o are rarely affected because of random inactivation of X chromosomes in each cell
T
In this X-linked d/o that begins before 5 y/o, weakness begins in the pelvic girdle muscles and progresses superiorly. YOu may see pseudohypertrophy of calf muscles due to fibrofatty replacement of muscle; cardiac myopathy. Often times kids will use the Gower's manuver, requiring assistance of the upper extremities to stand up, is characteristic (indicates proximal lower limb weakness)
Duchenne's muscular deficiency
Duchenne's muscular deficiency is an X linked d/o that results from a frame-shift mutation that deletes this gene which leads to accelerated mm breakdwon.
dystrophin gene

mneu: Duchenne's = Deleted Dystrophin
In this d/o the mutation of the dystrophin gene is less sever than Duchenne's
Becker's
fragile x syndrome is an x-linked defect affecting the methylation and expression of the ____ gene
FMR1
how common is fragile X
commmon
2nd most common cause of mental retardation
most common cause is down sydnrome
give some PE findings of fragile X
macro-orchidism (enlarged testes), long face w/ large jaw, large everted ears, and autism

mneu: Fragile X=eXtra-large testes, jaw, ears
fragile X syndrome is a ______ repeat d/o (CGC)n that may show genetic anticipation (germlike expansion in females).
triplet
Give 3 trinucleotide repeat expansion dz
HUNTINGton's dz, MYotonic dystrophy, FRIEDreich's ataxia, frafile X syndrome.

mneu: TRY (trinucleotide) HUNTING for MY FRIED eggs (X)
trinucleotide repeat expansion dz may show this which refers to increased disease severity and age of severity in successive generations
anticipation
Give 5 common congenital malformations
1) heart defects
2) hypospadias
3) cleft lip
4) congenital hip dislocation
5) spina bifida
6) Anencephaly
7) Pyloric stenosis
this common congenital malformation is associated with projectile vomiting
pyloric stenosis
give 3 autosomal trisomies
down syndrome
edwards' syndrome
patau's syndrome
give the genetics of Down syndrome
trisomy 21
how common is down syndrome
most common chromosomal d/o and cause of congenital mental retardation
give some physical exam findings of down syndrome
mental retardation, flat facial profile, prominant epicathal folds, simian crease, duodenal atresia, congenital heart dz (most common malformation is septum primum-type ASD due to endocardial cushion defects).
what dzs are people w/ down syndrome at risk for as they get older
alzheimer's dz (>35 y/o)
increase risk of ALL
give tips off in utero that a baby may be trisomy 21
decreased levels of alpha fetoprotein, inceased levels of beta hCG, increased nuchal translucency
95% of cases of trisomy 21 are due to this type of nondisjxn of homologous chromosomes
meiotic

4% of cases due to robertsonian translocation
1% due to Down mosaicism (no maternal association)
What is the risk of down syndrome in women < 20 y/o?
>45 y/o
1:1500
1:25
children with this autosomal trisomy have severe mental retardation, rocker bottom feet, low-set ears, micrognathia (small jaw), congenital heart dz, clenched hands, prominent occiput. Death usually occcurs within 1 year of birth
Edwards' syndrome
(trisomy 18)
1:8000

mneu: Election age (18)
children with this autosomal trisomy have severe mental retardation, microphthalmia, microcephaly, cleft lip/palate, abnormal forebrain sxs, polydactyly, congenital heart dz. Death usually occurs w/in 1 year of birth
Patau's syndrome
(trisomy 13)
1:6000

mneu: Pubety (13)
image p. 110 nondisjxn
--
findings of this d/o include microcephaly, severe mental retardation, high ptiched crying/mewing, epicanthal folds, cardiac abnormalities

what is the congenital deletion
short arm of chromosome 5
(46,XX or XY, 5p)

Cri-du-chat syndorme
Cleft palate, Abnormal facies, Thymic aplasia (T-cel deficiency), Cardiac defects, Hypocalcemia (secondary to parathyroid aplaisia)
22q11

CATCH-22
22q11 has variable presentation as these 2 syndromes
DiGeorge Sydnrome (thymic, parathyroid, and cardiac defects) or velocardiofacial syndrome (palate, facial, and cardiac defects)
what are the fat soluble vitamens
ADEK
this fat soluble vitamen is key in vision
A
this fat soluble vitamen is key for bone calcification and Ca+ homeostasis
D
this fat soluble vitamen is key in clotting
K
this fat soluble vitamen is a key antioxident
E
thiamine
B1
riboflavin
B2
niacin
B3
this water soluble viatamen is key for blood and neural development
folate
this fat soluble vitamen is key for the CNS and blood
B12 (cobalamin)
pyridoxine/Pyridoxal/Pyridoxamine
B6
the absorption of fat soluble vitamens is dependent on these 2 organs
gut(ilium) and pancreas
is toxicity more common in water soluble or fat soluble vitamens
fat
malabsorption syndromes (steatorrhea), such as cystic fibrosis and sprue, or mineral oil intake can cause these vitamin deficiencies
fat
Water soluble vitamens all wash out easily from the body except this vitamen that is stored in the liver
B12
B1
thiamine: TTP
B2
riboflavin: FAD, FMN
B3
niacin: NAD+
B5
Pantothenate: CoA
B12
cobalamin
C
ascorbic acid
pt presents with dermatitis, glossitis, and diarrhea. What vit deficiencies
B complex
this vitamen is a constituent of visual pigments (retinal)
A

mneu: RETINOL is vitamen A, so think RETIN-A (used topically for wrinkles and acne)
give 3 symptoms of vit A deficiency
night blindness, dry skin, impared immune response
give 3 symptoms of vit A excess
arthralgias, fatigue, headaches, skin changes, sore throat, alopecia
this vitamen fxs in thiamine pyrophosphate, a cofactor for oxidative carboxylation of alpha-keto acids (pyruvate, alpha ketogluterate) and a cofactor for transketolase in the HMP shunt
vitamen B1 (thiamine)
give 2 conditions that can result from vit B1 (thiamine) deficiency
Beriberi and Wernicke-Korsakoff syndrome

mneu: Ber1Ber1
this type of beriberi is characterized by polyneuritis and mm wasting
dry
this type of beriberi is characterized by high-output cardiac failure (dilated cardiomyopathy, edema
Wet
this vitamen is a cofactor in oxidation and reduction (e.g., FADH2)
vitamen B2 (riboflavin)
give a few signs of vit B2 (riboflavin) deficiency
angular stomatitis, cheilosis, corneal vasculation

mneu: the 2 C's
FAD & FMN are derived from this vitamen
riboFlavin
B2=___ATP
2
this vitamen is a constituent of NAD+, NADP+ (used in redox reactions). Derived from tryptophan using vit B6
vitamen B3 (niacin)
give the 3 Ds of Pellagra
diarrhea, dermatitis, dementia (also beefy glossitis)
deficiency of vit B3 (niacin can be caused by hartnup dz. Why?
decreased tryptophan absorption
deficiency of vit B3 (niacin can be caused by malignant carcinoid syndrome. Why?
increased tryptophan metabolism
deficiency of vit B3 (niacin can be caused by INH. Why
decrease vit B6
NAD is derived from _______
Niacin
B3=__ATP
3
this vitamne fxs as a constituent of CoaA (a cofactor for acyl transfors) and component of fatty acid synthase.
vitamen B5 (pantothenate)

mneu: Pantothen-A is in CoA
give some signs of vit B5 deficiencies
dermatitis, enteritis, alopecia, adrenal insufficiency
this vitamen fxs converted to pyridoxal pyridoxal phosphate, a cofactor used in transamination (e.g., ALT & AST), decarboxylation, and heme synthesis
vitamen B6 (pyridoxine)
give signs of vit B6 (pyridoxine)
convulsions, hyperirritability (deficiency inducible by INH and oral contraceptives), peripheral neuropathy.
this vitamen is a cofactor for homocysteine methylation (transfers CH3 groups as methylcobalamin) and methylmalonyl-CoA handling.
vitamin B12 (cobalamin)
vitamen B12 is stored primarily in this organ
liver
vitamme B12 is synthesized only by microorganisms and is found only in this type of food
animal products.
vitamen B12 is usually caused by malabsorption-- give a few examples
sprue, enteritis, Diphyllobothrium latum
vitamen B12 can be caused by pernicious anemia which is caused by a lack of this
intrinsic factor
vit B12 can be caused by absense of terminal ileum for example in this GI dz
chron's dz
this test is used to detect vit B12
schillng test
abnormal myelin is seen in B12 deficiency, possibly due to decreased_______ or increased ________ (from metabolism of accumulated methylmalonyl-CoA)
methionine
methylmalonic acid
this is the most common vitamen deficiency in the US
folic acid
this vit fxs in coenzyme (tetrahydrofolate) for 1 carbon transfer, involved in methylation reactions. It is important for synthesis of nitrogenous bases in DNA and RNA
folic acid
give some signs and symptoms of folic acid deficiencies
macrocytic, megaloblastic anemia (often no neuro symptoms, as opposed to vitB12
what kind of foods are high in folate
green leafy veggies

mneu: FOLate from FOLiage
supliment folic acid when
early pregnancy-reduces neural tube defects
PABA is the folic acid precursor in bacteria. these antimicrobials work because they are PABA analogs
sulfa drugs and dapsone
this vitamen is a cofactor for carboxylations:
1) Pyruvate ->oxaloacetate
2) Acetyl-CoA ->malonyl-CoA
3) Proprionyl-CoA ->methhylmalonyl CoA
biotin
biotin deficiency can be caused by using these drugs or eating these
antibiotics
raw eggs

mneu: AVIDin in egg whites AVIDly binds biotin
give some symptoms of biotin deficiency
dermatitis, enteritis
give some signs of vit C deficiency
scurvy--swollen gumbs, bruising, anemia, poor wound healing
vit C is necessary for hydroxylation of _____ and _____ in collagen synthesis
proline
lysine

mneu: vit C Cross-links collagen. British sailors carried limes to prevent scury (origin of word "limey"
vit C facilitates absorption of this nutrient
Fe++
(keeps it in a reduced state-more absorpable)
vit C is necassary as a cofactor for dopimine in conversion to this neurotransmitter
NE
this is the form of vit D found in milk
D2 (ergocalciferol)
this is the form of vit D formed in sun-exposed skin
D3 (cholecalciferol)
this is the storage form of vit D
25-OHD3
this is the active form of vit D
25-(OH)2D3
give some signs of vit D deficiency
rickets in children (bending bones), osteomalacia in adults (soft bones) and hypocalcemic tetany
what is the fx of vit D
increase intestinal absorption of Ca++ & phosphate
what are some signs of vit D excess
hypercalcemia, loss of appetite, stupor.
what dz might you see excess vit D in
sarcoidosis
(dz where epitheliod macrophages convert vitD into its active form
vit E deficincy results in a fragility of these blood cells
erythrocytes

mneu: vit E is for Erythrocytes
what is the fx of vit E
it is an antioxidant that protects erythrocytes from hemolysis
this vitamen funcitons to catalyze gamma-carboxylation of glutamic acid residues on various proteins concerned with blood clotting.
vit K

mneu: K is for Koagulation
How is vit K synthesized. What drugs can cause vitK deficiency
intestinal flora
prolonged use of broad spectrum antibiotics
vit K deficiency can result in this problem in neonates (what would PT, PTT, & bleeding time be)
neonatal hemorrhage w/ increased PT and increased aPTT but normal bleeding time
what are the vit K dependent clotting factors
II,VII,IX,X and protein C & S
this drug is a vitK antagonist
Warfarin
give a few signs of zinc deficiency
delayed wound healing, hypogonadism, decreased axillary, facial, and pubic hair. It may predispose to alcoholic cirrhosis.
etoh metabolism [p.115]
--
this enzyme catalyzes EtOh to acetaldehyde and reduces NAD+ to NADH
alcohol dehydrogenase
this enzyme catalyzes acetaldehyde to Acetate and reduces NAD+ to NADH
acetaldehyde dehydrogenase
what is the limiting reagent in etoh metabolism
NAD+
what is the kinetics of alcohol dehydrogenase
zero order
how does disulfram (antabuse)work.
inhibits acetaldehyde dehydrogenase--acetaldehyde accumulates contributing to hangover symptoms
describe ethanol hypoglycemia
ethanol metabolism increases NADH/NAD+ ratio in the liver, causing diversion of pyruvate to lactate and OAA to malate, thereby inhibiting gluconeogenesis and leading to hypoglycemia.
altered NADH/NAD+ ratio in the liver is responsible for this change seen in chronic alchololics
hepatic fatty change (hepatocellular steatosis)-shunting away from glycolysis and toward fatty acid synthesis
image. p. 115 etoh hypoglycemia
--
this is protein malnutrition resulting in skin lesions, edema, liver malfxn (fatty change). Clinical picture is a small child w/ a swollen belly
kwashiorkor

mneu: resutls from a protein deficient MEAL
Malabsorption
Edema
Anemia
Liver (fatty
this results from protein-calorie malnutrition resulting in tissue wasting
marasmus