Biochem 1 USMLE Flashcards
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
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 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
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
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)
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
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)
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
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
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+)
Describe 1st step of B-oxidation of very long chain FA in Peroxisomes?
1st step of of B-oxidation is catalized by an FAD containing oxidase. e- are transfered from FADH2 to O2 which is then reduced to H2O2
Takes place in peroxisome because H2O2 is produced
What are similarities & differences of mitochondrial vs peroxisomal B-oxidation?
Both generate FADH2 & NADH but
Peroxisomal is less efficient because FADH can’t get through peroxisomal membrane (must be oxidized by O2)
Why do peroxysomal B-oxidation?
very long chain FA cannot cross mit membrane, must be broken up by peroxysomes
Describe oxydation of phytanic acid?
a peroxysomal alpha hydroxylase oxidizes the alpha carbon so that B oxidation can occur.
Refsum’s disease
alpha oxidase enzyme is defective so we cannot break down phytanic acid
w-oxidation of FA
converts FA to dicarboxylic acids. Results in DC urea. Which is diagnostic for problem w/ B oxidation
4 steps of B-oxidation
1) Oxidation (ACoA dehyd)
2) Hydration (enol CoA hyd)
3) Oxidation(B hydroxy CoA hyd)
4) Cleavage (B keto thiolase)
Metabolism of Monosaturated Fats
2-3 enol-CoA isomerase - converts cis bond to trans
Metabolism of Polyunsaturated Fats
2-3 enol-CoA isomerase - converts cis bond to trans
2-4 dienol Co A reductase – reduces one of the double bonds
Propynyl Co A pathway
Propionyl CoA to Succinyl CoA. 1st step involves Propionyl CoA carboxylase (ABC enzyme) conversionof Propionyl CoA to methmylmalonyl CoA. Last step involves methyl-Malonyl CoA mutase conversion of Methylmalonyl CoA to Succinyl CoA. This last enzyme requires B12 therefore build up of Methylmalonyl CoA is diagnostic for B12 deficiency.
ABC enzymes
ABC
Pyruvate carboxylase -
Acetyl CoA carboxylase -
Propionyl CoA carboxylase -
MCAD deficiency
B oxidation in liver tissue in order for gluconeogenesis – if can’t do B-oxidation – hypoglycemic shock;
Feed child, replenished glycogen stores, in night using glycogen stores, next morning feed – child never in hard glucagon world. Never know about deficiency. Using liver glycogen always. When glycogen stores don’t get built up child needs to do gluconeogenis need to do B oxidation – usually dies in middle of night.
3 ketone bodies:
1) Acetoacetate can covert to:
2) Acetone (volitile)
3) D-B Hydroxybutyrate (more stable)
Why are ketone bodies made in liver cells only?
HMG Co A synthase –makes ketone bodies and found only in liver mitochondria
Why are ketone bodies broken down in tissues other than the liver
B-ketoacyl- CoA transferase is found in mitochondria outside liver -allows extrahepatic tissues to break ketone bodies down
Fuel for Brain
1) 24 hours
2) day 2-7
3) After 1 week
1) glycogen
2) protein (mostly glucose from gluconeogenesis but some ketone bodies)
3) Fat & small amount of protein-mostly ketone bodies but some glucose from gluconeogenesis
