Biochem Flashcards
1
Q
17-alpha-hydroxylase deficiency
hormone deficiencies + s/s
A
low corticosteroids + androgens; high aldosterone
(impairs pregnenolone / progesterone 17-hydroxylation)
causes CAH with ambiguous genitalia in males, sodium retention and hypertension in both sexes
2
Q
21-hydroxylase deficiency
hormone deficiencies + s/s
A
1 CAH; increased androgens; low cortisol + aldosterone
ambiguous genitalia in females; salt-wasting + hypotension in both sexes
3
Q
Retinoblastoma protein
regulatory function? and how is it regulated itself?
A
controls (inhibits) G1 to S transition
when HYPOphosphorylated, Rb is active and cell remains in G0
growth factor stim > cyclin D, E and CDK 4, 6 > Rb is HYPERphosphorylated + inactive > releases E2F transcription factor > G1 to S occurs
4
Q
Recurrent bouts of:
Diffuse abd. pain (+/- const, naus, decr. sounds) Neuro sx (tingling, sleep issues, diff. concentrating) Dark red urine
Likely dx, pathogenesis, tx
A
Acute Intermittent Porphyria
AD deficiency of porphobilinogen deaminase
Tx with heminor glucoseto decr. ALA synthase activity
5
Q
Acute intermittent porphyria attacks can be triggered by induction ofwhich enzymebywhich inducers?
A
ALA Synthase
drugs: phenobarb, griseofulvin, phenytoin alcohol smoking progesterone (ie puberty) low-calorie diet
6
Q
How long does glycogenolysis maintain blood glucose in the fasting state?
A
12-18 hours
7
Q
When does gluconeogenesis take over in maintenance of blood glucose during fasting?
A
after 12-18 hours, when glycogen stores are depleted
8
Q
Which 3 enzymatic reactions in glycolysis + TCA are irreversible and must be bypassed by unique enzymes in gluconeogenesis?
A
pyruvate dehydrogenase
phosphofructokinase
hexokinase
9
Q
Which FOUR enzymes bypass irreversible glycolysis/TCA steps in gluconeogenesis?
A
- PYRUVATE CARBOXYLASE
(pyruvate > OAA (biotin)
OAA > Malate via MDH, then malate leaves mitoch and > OAA via cytosolic MDH)
- PEP Carboxykinase - (OAA > PEP)
- Fructose-1,6-bisphosphatase
- Glucose-6-phosphatase
10
Q
What is the Shine-Dalgarno sequence?
A
an initiation sequence on PROKARYOTIC mRNA upstream of the AUG start codon
consists of AGGAGGU > binds the UCCUCCA of the 16s rRNA on the 30s subunit
11
Q
What is the eukaryotic equivalent of the Shine-Dalgarno sequence?
A
Kozak sequence consisting of GCCGCCRCC where R is a purine (A or G)
it is immediately upstream of the start codon (GCCGCCRCCAUG) and downstream of the 5’methyl-G cap
12
Q
what mediates co-translational protein targeting?
A
the N-terminal AA sequence
recognized by “signal recognition particle” that transports protein to the rER
13
Q
Polyol pathway
oversaturation in hyperglycemia results in formation of 2 products via 2 enzymes
A
ALDOSE REDUCTASE makes SORBITOL from glucose (NADPH)
SORBITOL DEHYDROGENASE makes FRUCTOSE from sorbitol (NAD+)
(sorbitol > fructose conversion occurs fine at normal glucose conc. but in hyperglycemia it overwhelms SDH and sorbitol accumulates)
14
Q
Hormone Sensitive Lipase
activators? inhibitors? effects?
(hint: stimulates two metabolic pathways by release of their substrates)
A
HSL is on fat cells
Activated by: catecholamines, glucagon, ACTH
(Gs > PKA > phosphorylation of HSL)
Inhibited by: insulin
Breaks down TAGs to GLYCEROL (>gluconeogenesis) and FFAs (>ketogenesis)
15
Q
Base excision repair
what kind of defect does it repair?
Mechanism (order of enzymes)?
A
Repairs CYTOSINE DEAMINATION ( > Uracil in DNA) or other improper bases
- GLYCOSYLASE - cleaves wrong base
- ENDONUCLEASE - cleaves 5’ end
- LYASE - cleaves 3’ sugar-P
- POLYMERASE - fills gap
- LIGASE - seals nick
“gel pill”
16
Q
where does Pro and Lys hydroxylation of collagen alpha-chains occur?
A
in the RER
via prolyl / lysyl hydroxylases with vitamin C cofactor
17
Q
how do procollagen molecules become tropocollagen? and where?
A
N- and C-terminal propeptides are cleaved by extracellular PROCOLLAGEN PEPTIDASE to form tropocollagen
18
Q
what occurs with tropocollagen to form collagen fibrils? where + what enzyme?
A
monomers self assemble in the ECM and are CROSSLINKED by LYSYL OXIDASE (with copper)
19
Q
eukaryotic gene promoters (2)
what are they? where are they? what do they bind?
A
CAAT box - 70-80 bases upstream from transcription start
Hogness / TATA box - 25 bases upstream from transcription start
binding sites for general TFs and RNA polymerase II
20
Q
Retinoblastoma protein function
A
TUMOR SUPPRESSOR on chr. 13q14
hypophosphorylated > active > prevents G1 to S transition
hyperphosphorylated = opposite
21
Q
Hereditary Homocystinuria
inheritance, enzyme + cofactor
(enzyme sequence)
A
AR deficiency of
CYSTATHIONINE BETA SYNTHASE which uses B6 (Pyridoxine) as a cofactor
pyridoxine in hi doses can be used as tx in 50% pts
(Cystathionine beta synthase removes HCys from the methionine cycle, forming cystathionine; then cystathionase forms cysteine)
22
Q
Hereditary Homcystinuria
s/s + complications
A
present age 3-10
INFERIOR lens subluxation
intellectual disability
Marfanoid habitus
thromboembolism (brain, heart, kidneys) #1 COD
23
Q
Alkaptonuria
inheritance? AA affected?
A
AR disorder of TYROSINE metabolism
24
Q
Alkaptonuria
enzyme affected? intermediate accumulated?
where would the final intermediate in this pathway end up metabolically?
A
(AR disorder of tyrosine metabolism)
HOMOGENTISIC ACID DIOXYGENASE is deficient, leading to HOMOGENTISATE accumulation
pathway eventually forms FUMARATE which enters TCA CYCLE
25
Alkaptonuria
s/s? what does built up metabolite bind?
built up homogentisate binds COLLAGEN in CT, tendons + cartilage > ...
OCHRONOSIS - blue-black ears, nose + cheeks
OCHRONOTIC ARTHROPATHY - adult onset usually
urine becomes BLACK after sitting
26
#2 cause of congenital adrenal hyperplasia?
enzyme? s/s?
11B-hydroxylase deficiency
shunts production towards androgens, but 21-OHase is still intact so 11-deoxycorticosterone (a weak MC) is still made
in girls > virilization with high BP, hypokalemia
in boys > just aldo effects
27
which step of TCA cycle creates GTP?
Succinate thiokinase
(aka succinyl-coa synthetase)
Succinyl-CoA > succinate (GDP > GTP)
28
Other than transphosphorylation of ADP to ATP...
what can GTP formed in the TCA do?
is used by specific GTP-hydrolyzing enzymes like...
PEP carboxykinase (gluconeogenesis)
29
pentose phosphate pathway. IC location?
cytosol
30
FA synthesis pathway. IC location?
cytosol
31
2 thiamine dependent steps of TCA
what other paths are thiamine-dependent? which enzymes? (2)
pyruvate dehydrogenase complex
alpha keto glutarate DH complex
PP pathway - TRANSKETOLASE needs thiamine
BCKA Dehydrogenase - deficient in maple syrup urine disease
32
irreversible part of pentose phosphate pathway makes what?
for what processes?
the "oxidative" part of PPP - converts G6P to R5P in 2 steps with each step CREATING NADPH for...
cholesterol + FA synth
and
glutathione antioxidative mechanism
33
reversible part of PPP makes what?
for what 2 processes?
the "nonoxidative" part of PPP uses ribulose-5-phosphate to make...
RIBOSE-5-PHOSPHATE for NUCLEOTIDE SYNTHESIS
FRUCTOSE-6-PHOSPHATE or GLYCERALDEHYDE-3-P for GLYCOLYSIS
enzymes are TRANSKETOLASE and TRANSALDOLASE (cytosolic)
34
what is the metabolic advantage of the REVERSIBILITY of the non-oxidative steps of the PPP?
when R5P is in excess, PPP can use it to make glycolytic intermediates
when glycolytic intermediates are in excess, PPP can use them to make R5P
35
DNA Polymerase I activity
| prokaryotes
unique activity is 5'-3' EXONUCLEASE which functions to REMOVE RNA PRIMER
also has 3'-5' exonuclease, as do ALL prokaryotic DNA polymerases
36
DNA Polymerase III activity
| prokaryotes
5' to 3' polymerase
3' to 5' exonuclease
main polymerase of prokaryotic replication
37
DNA gyrase
other name, function, inhibitor
Topoisomerase II (DNA gyrase is name for it in prok.)
introduces NEGATIVE SUPERCOILS in circular DNA to relieve tension made by strand unwinding
fluoroquinolones inhibit it
38
Inclusion Cell Disease
inheritance? defect?
AR inheritance
defect of lysosomal storage
defective PHOSPHOTRANSFERASE enzyme can not phosphorylate MANNOSE residues on glycoproteins in Golgi headed to lysosomes
39
Inclusion Cell Disease
s/s?
think eyes, msk system, RES
```
failure to thrive + dev delay
COARSE FACIAL features
CORNEAL CLOUDING
HSmegaly
restricted JOINT MOBILITY
GINGIVAL hyperplasia
CLAW HAND deformity
Kyphoscoliosis
```
40
Path of glucagon's effect on glycogen metabolism
Glucagon > glucagon receptor > ***Gs***
PKA phosphorylates PHOSPHORYLASE KINASE which then phosphorylates "GLYCOGEN PHOSPHORYLASE B" (inactive form) to form glycogen phosphorylase a (active form)
glycogen phosphorylase a cleaves glycogen to release GLUCOSE-1-P from the terminal alpha-1,4-glycosidic bond
41
how can muscle "glycogen phosphorylase b" have the same action as "glycogen phosphorylase a" (the active P-ated form)?
allosteric modulation by AMP
changes it from tense to relaxed, functional state
42
Hunter syndrome
inheritance? enzyme? accumulation
mucopolysaccharidosis type II
XR inheritance
lack of iduronate-2-sulfatase
heparan and dermatan sulfate (GAGs) accumulate in all tissues
43
Hunter syndrome
s/s? dx?
```
progressive facial abnormalities + slow growth in infant
mental retardation
coarse facial features
HSmegaly
joint stiffness
```
urine GAGs
enzyme activity in serum, WBC or fibroblast (I2S)
genetic analysis
44
which ribosomal enzyme forms peptide bonds btwn AAs?
peptidyl transferase
45
what tissues have both ALDOSE REDUCTASE and SORBITOL DEHYDROGENASE activity?
they "LOSe" sorbitol
```
liver
ovaries
seminal vesicles (sem ves make the fructose that goes into semen)
```
46
what tissues have only aldose reductase activity?
sorbitol is LRKN in these tissues
lens, retina, kidney, neurons
47
what is the first enzyme in gluconeogenesis?
what metabolic intermediate stimulates it?
and what does this intermediate inhibit?
pyruvate carboxylase (uses biotin + CO2; makes oxaloacetate)
ACETYL-CoA (eg, from beta oxidation) stimulates it
acetyl-coa also inhibits pyruvate dehydrogenase (as it is a product of PDH)
48
3 questions... During the starvation state...
what metabolic intermediate (1) is converted to a gluconeogenic substrate (2) in MUSCLE?
what allosteric effect (3) does that gluconeogenic substrate have?
In muscle, 1) PYRUVATE is transaminated to form 2) ALANINE which is then transported to the liver for reconversion to pyruvate and use in gluconeogenesis
Alanine allosterically 3) INHIBITS PYRUVATE KINASE, to prevent PEP from being consumed by glycolysis
(remember Pyr kinase catalyzes PEP + ADP > Pyruvate + ATP)
49
Main ALLOSTERIC ACTIVATOR of PYRUVATE KINASE
F-1,6-BP
"feedforward" stimulation
50
Main COVALENT MODIFIERS of PYRUVATE KINASE
ie, things that cause phosphorylation / dephosphorylation (hint: molecules that have lots of downstream cellular effects via surface receptors)
inactivators:
GLUCAGON + EPINEPHRINE will activate PKA (Gs) > phosphorylate and inactivate pyruvate kinase (think: fasting state hormones > no glycolysis)
activators:
INSULIN will activate "phosphoprotein phosphatase I" which dephosphorylates + activates pyruvate kinase
51
3 answers:
What metabolic intermediate (1) that is an INDICATOR OF HIGH CELLULAR ENERGY STORES is a positive regulator of two enzymes (2+3)?
Hint: one enzyme is involved in well-fed state activities, the other in starvation activities.
1. CITRATE - indicator of high cellular energy stores
2. ACETYL-COA CARBOXYLASE - main enzyme of FA synth (well-fed state); makes malonyl-CoA
3. FRUCTOSE-1,6-BISPHOSPHATASE - gluconeogenesis (starvation state)
52
Main regulator of phosphofructokinase-1 and its gluconeogenetic counterpart enzyme?
How does regulation work?
FRUCTOSE-2,6-BISPHOSPHATE - made by pfk-2
high levels of f-2,6-bp will ACTIVATE PFK-1 and INHIBIT F-1,6-BP-ASE (activate glycolysis and inhibit gluconeogenesis)
low levels will "disinhibit" F-1,6-BP-ASE and thus activate gluconeogenesis
53
What two enzymes does B12 act as a cofactor for?
Deficiency results in buildup of what? (2)
METHYLMALONYL-CoA MUTASE - impaired synthesis of succinyl-CoA results in buildup of METHYLMALONIC ACID which impairs myelin synthesis
METHIONINE SYNTHASE - prevents HCys conversion to Met, causing HOMOCYSTEINE buildup (also prevents methyl-THF to THF conversion, impairing DNA synth)
54
Erythrocyte TRANSKETOLASE activity is reduced in deficiency of what?
which causes what?
Vitamin B1 - Thiamine
deficiency causes Wernicke-Korsakoff and BeriBeri
(transketolase is an HMP shunt enzyme)
55
in the WELL-FED STATE, what citrate cycle enzyme is inhibited and why? what is the result?
ISOCITRATE DEHYDROGENASE is inhibited by high levels of ATP
this causes a buildup of CITRATE
56
how does citrate leave the citrate cycle during the well-fed state, where does it go + what does it do?
CITRATE SHUTTLE transfers it from mitochondria to CYTOSOL where it is cleaved by ATP CITRATE LYASE to form ACETYL-CoA for FA SYNTH
57
what two things cause upregulation of the rate-limiting step of fatty acid synthesis?
and what does this initial step create?
CITRATE and INSULIN both upregulate ACETYL-CoA CARBOXYLASE
ACC creates MALONYL-CoA
58
After formation of malonyl-CoA by ACC how are fatty acids synthesized? Enzyme etc
FATTY ACID SYNTHASE catalyzes a CONDENSATION of malonyl-CoA and acetyl-CoA to create a 4-C molecule that will undergo more condensations form a 16C palmitic acid
59
How does fatty acid synthesis regulate fatty acid beta-oxidation?
MALONYL-CoA formed by ACC has an inhibitory effect on CARNITINE ACYLTRANSFERASE, which prevents movement of fatty acids into the mitochondrial matrix
60
WHAT removes introns from mRNA and HOW CAN IT RECOGNIZE WHERE to remove them from?
"Spliceosomes" - complexes of snRNPs and other proteins
introns contain two signals for splicing:
5' splice site - GU
3' splice site - AG
61
what are the repeats in telomeres?
added by what enzyme with what kind of action?
TTAGGG repeats
added by TELOMERASE - an RNA-dependent DNA polymerase
62
Vitamin B1 deficiency in NON-ALCOHOLIC adults
2 types - what are they?
Thiamine deficiency causes
1. Dry beriberi - SYMMETRICAL peripheral neuropathy of distal extremities (both sensory + motor)
2. Wet beriberi - periph. neuropathy plus HEART INVOLVEMENT ... includes cardiomyopathy, HO-CHF, peripheral edema and tachycardia
63
Vitamin B1 deficiency in babies
infantile beriberi - presents at 2-3 months
a "fulminant cardiac syndrome" with cardiomegaly, tachycardia, cyanosis, dyspnea and vomiting
64
Fabry
(inheritance, deficiency, accumulation, sx)
(sx have an early triad + late fx)
XR - the only non-auto-recessive sphingolipidosis!
alpha-galactosidase
globotriaosylceramide (aka ceramide TRIHEXoside)
early: angiokeratoma, periph neuropathy, hypohidrosis
late: CV and RENAL disease
("the spotted galactic fairy put 3 hexes on her X Ryan's heart so he can't feel his hands, sweat or pee")
65
Tay-Sachs
(inheritance, deficiency, accumulation, sx, special histo)
(differentiation from other similar disease)
AR
hexosaminidase A ... (tAy saX - heXosaminidase A)
GM2 ganglioside
macular cherry-red spot
progressive neurodegeneration
(NO hepatosplenomegaly! diff from N-P)
"onion skin" lysosomes
66
Gaucher
| inheritance, deficiency, accumulation, sx and HISTO
AR - #1 sphingolipidosis
glucocerebrosidase (tx with recombinant)
glucocerebroside
HSmegaly
pancytopenia
bone pain/osteopenia/femur avascular necrosis
Gaucher cells - crumpled paper lipid laden macros
67
Niemann-Pick
(inheritance, deficiency, accumulation, sx and HISTO)
(differentiation)
AR
SPHINGOMYELINASE ("No Man Picks his nose with his sphinger")
sphingomyelin
macular cherry-red spot
progressive neurodegeneration
HSmegaly (unlike Tay-Sachs with no hsmegaly)
lipid-laden macros
68
Krabbe
| inheritance, deficiency, accumulation, sx and HISTO
AR
galactocerebrosidase
galactocerebroside + psychosine
developmental delay - stupid
peripheral neuropathy - can't feel hands
optic atrophy - can't see
globoid cells + oligodendrocyte destruction
("the slow psycho galactic crab can't see or feel his hands")
69
Metachromatic Leukodystrophy
| inheritance, deficiency, accumulation, sx
AR
arylsulfatase A
cerebroside sulfate
CNS / PNS demyelination (LEUKOdystrophy) with...
ataxia
dementia
70
3 main processes that occur to precursor mRNA (heterogenous nuclear RNA; hnRNA) before it leaves the nucleus
1. 5'-methylguanosine capping
2. 3' polyadenylation
3. intron splicing
71
2 main processes that mature mRNA might undergo after it leaves the nucleus
1. Translation at ribosomes
2. Interaction with "P BODIES" - cytoplasmic foci involved in translation repression and mRNA decay; contain RNA exonucleases, mRNA decapping enzymes, and miRNA-induced silencing; sometimes "store" mRNA for later use
72
Polyadenylation
what enzyme? what signal sequence on preMRNA? how many adenines?
POLYADENYLATE POLYMERASE complex recognizes an AAUAAA sequence, cleaves downstream and adds 20-250 adenines
73
Capping of preMRNA
2 enzymes
GUANYLYLTRANSFERASE - adds 5' GTP
GUANINE-7-METHYLTRANSFERASE - methylates
74
What are c-Jun and c-FOS?
nuclear transcription factors
bind DNA via a leucine zipper motif
75
Hereditary Orotic Aciduria
inheritance? enzyme?
AR inheritance
UMP synthase (enzyme in de novo pyrimidine synthesis)
76
Hereditary Orotic Aciduria
3 clinical signs
1. Mental + physical developmental delay
2. Megaloblastic anemia
3. Elevated urinary orotic acid
77
Hereditary Orotic Aciduria
Differential dx?
Tx?
Ornithine transcarbamylase defic. also has high orotate in urine but have FAILURE TO THRIVE and HYPERAMMONEMIA with encephalopathy in first few weeks
Tx with URIDINE (defic. of UMP synthase > uridine can be phosphorylated to UMP by nucleoside kinases)
78
what 2 properties of ELASTIN give it is elasticity?
1. high content of NONPOLAR amino acids (glycine, alanine, valine)
2. DESMOSINE CROSS-LINKS - between deaminated Lysines (via lysyl oxidase + Cu) on neighboring
79
BCKA Dehydrogenase
metabolizes Val, Leu and Ile (BCAAs) into what?
2 products
Leu becomes ACETYL-CoA ( > TCA cycle)
Val, Ile become PROPIONYL-CoA ( > methylmalonyl-Coa > Succinyl-CoA > TCA cycle)
80
Maple Syrup Urine Disease / BCKA DH defic.
S/S? Consequence if untreated?
Neurotoxicity - seizures, lethargy, irritability, poor feeding
BRAIN SWELLING can result in death
81
Deficiency other than Phe hydroxylase that can result in PKU?
Tetrahydrobiopterin - a cofactor for Phe hydroxylase
82
Vitamin B6 / pyridoxine
involved in what 4 biochem processes?
1. Transamination - AAs
2. Decarboxylation - AAs
3. Heme synth
4. NT synth
83
Arginase catalyzes what reaction?
formation of UREA and ORNITHINE from arginine
84
Arginase Deficiency
presentation (3)?
labs (one positive and one negative test)?
tx (2)?
- SPASTIC DIPLEGIA - bilateral leg stiffness
- INVOLUNTARY MOVEMENTS - choreoathetoid
- GROWTH DELAY
- high ARGININE in plasma/CSF
- NORMAL ammonia levels
- low protein diet (esp Arg)
- synthetic protein without arginine improves sx + decreases arginine levels
85
What two urea cycle disorders result in buildup of orotic acid? Why?
1. CITRULLINEMIA - defic. of argininosuccinate synthase
2. ORNITHINE TRANSCARBAMYLASE defic.
both result in buildup of CARBAMOYL PHOSPHATE which is broken down by DIHYDROOROTATE DH into orotic acid
(diff from UMP synthase defic. aka hereditary orotic aciduria because they both have hyperammonemia as well)
86
When is blood glucose maintained primarily by hepatic glycogenolysis?
from 4-16 hours after last meal
over this time glycogenolysis slowly decreases and gluconeogenesis slowly increases
87
When is blood glucose primarily maintained by hepatic gluconeogenesis?
about 16-48 hours after last meal
glycogenolysis wanes starting at 16 hours
88
When is blood glucose maintained by BOTH HEPATIC and RENAL gluconeogenesis?
from 2 days after last meal
up to ~24 days brain uses mostly glucose, partly ketones
after ~24 days brain uses mostly ketones
89
Long-chain acyl-CoA DH deficiency
s/s?
Lethargy, feeding issues, HYPOGLYCEMIA, HYPOTONIA, liver problems (megaly), retinal issues
triggered by fasting or infections
LCFAs or metabolites build up in tissues + cause damage
90
Long-chain acyl-CoA DH deficiency
serum (3) + urine changes (2)?
tx?
serum - low glucose, ketones + carnitine
urine - low ketones and HIGH DICARBOXYLIC ACIDS
glucose and MCTs for tx
91
an EM img of the cell of a patient with a DEFECT IN VESICLE TRAFFICKING TO GOLGI would show what?
Dilated RER
proteins are not properly trafficked on past the RER so accumulate there
92
What TWO TYPES OF SACCHARIDES on which THREE AMINO ACIDS are modified by the Golgi for trafficking?
N-oligosaccharides on Asparagine
O-oligosaccharides on Serine, Threonine
93
What molecule is present on proteins to direct them to lysosomes?
mannose-6-phosphate
protein is glycosylated with mannose, then phosphorylated by N-acetylglucosaminyl-1-phosphotransferase (defective in I-cell disease)
94
What molecule helps proteins target the RER from ribosomes?
SRP - signal recognition particle
a ribonucleoprotein abundant in cytosol
if absent proteins accumulate in cytosol
95
What is the function of an endosome?
"sorting center" directs stuff from out of cell or Golgi to either lysosomes or back to membrane/Golgi
96
What are the two VESICULAR TRAFFICKING PROTEINS for anterograde/retrograde Golgi transport?
COP-II - anterograde; from ER to cis-Golgi
COP-I - retrograde; from cis-Golgi to ER
"two steps forward, one step back"
97
What is the VESICULAR TRAFFICKING PROTEIN for movement from the trans-Golgi to lysosomes/plasma membrane?
Clathrin
98
What biochemical process is responsible for muscle protein wasting in non-use atrophy?
polyubiquitination
99
What is the more severe mucopolysaccharidosis?
enzyme? inheritance? s/s?
Hurler syndrome - AR alpha-L-iduronidase
heparan + dermatan sulfate accumulate
- Dev delay
- Gargoylism
- Airway obstruction
- Corneal clouding
- HSM
(DGACH)
100
What is the less severe mucopolysaccharidosis?
enzyme? inheritance? s/s?
Hunter syndrome - XR iduronate-2-sulfatase
same accumulations
- Milder Hurler symptoms PLUS AGGRESSION and WITHOUT CORNEAL CLOUDING
- Joint stiffness
(DGAAH = dev delay, gargoylism, airway obstruction, aggression, HSM)
101
vitamin deficiencies in CF patient
what kind?
fat-soluble due to exocrine lipase insufficiency
A, D, E, K
102
Vitamin E excess
what two sx?
1. ENTEROCOLITIS in infants
| 2. Enhanced ANTICOAGULATION with WARFARIN - due to altered vit K metabolism
103
Vitamin E deficiency
s/s?
- HEMOLYTIC ANEMIA and ACANTHOCYTOSIS - impaired defense against lipid peroxidation in membranes
- MUSCLE WEAKNESS
- POSTERIOR COLUMN / SPINOCEREBELLAR TRACT DEMYELINATION - peripheral neuropathy and ataxia
(looks like B12 defic without megaloblastic anemia, hypersegmented neutros or incr. methylmalonic acid)
-
104
What is an open reading frame?
a continuous stretch of codons that contains a start codon and a stop codon
105
The PRESENCE OF WHAT can allow an mRNA lacking a 5'-MG cap to still be translated?
an INTERNAL RIBOSOME ENTRY SITE
5' caps regulate: 1) nuclear export, 2) degradation prevention, 3) translation promotion, and 4) 5' proximal intron excision
106
What in the ETC does carbon monoxide inhibit?
it has lots of names, which is super stupid
cytochrome c OXIDASE
aka complex IV
aka cytochrome a-a3
(so note this is NOT cytochrome C itself, but cyt C oxidase)
107
RNA Polymerase I in eukaryotes makes what?
ribosomal RNA
18S, 5.8S and 28S
(all but one rRNA made by RNA pol I ... 5S made by RNA pol III)
108
RNA Polymerase II in eukaryotes makes what? (3)
1. mRNA
2. snRNA - splicing + transcription regulation
3. miRNA - gene silencing (translation arrest/mRNA degradation)
109
RNA polymerase III in eukaryotes makes what? (2)
1. tRNA
| 2. the 5s ribosomal RNA
110
3 important intermediates yielded by beta-oxidation
1) FADH2 and 2) NADH, both for ATP production in etc
| 3) acetyl-CoA for use in TCA cycle or ketogenesis
111
Difference in timeline of ketone body use in adults vs. children
adults - require 1-2 days fasting before ketogenesis is significant
kids - lower glucose reserves; ketogenesis begins in 8-10 hours
112
Medium-Chain Acyl-CoA DH deficiency
S/S (6)?
what accumulates?
vomiting, lethargy
seizures, coma
liver dysfunction w/ mild hm
HYPERAMMONEMIA
"hypoketotic hypoglycemia" - with accumulated fatty acyl-carnitines in blood
tx by avoiding fasting + give glucose during infections
113
Primary Carnitine Deficiency
S/s
labs
complication (1)
"hypoketotic hypoglycemia" with WEAKNESS and HYPOTONIA
toxic accumulation of LCFAs
MUSCLE TRIGLYCERIDES are elevated
can cause CARDIOMYOPATHY
114
Galactokinase deficiency - s/s
cataracts and (rarely) pseudotumor cerebri
due to galactitol buildup
115
Galactose-1-phosphate uridyl transferase (GALT) deficiency
s/s
"Galactosemia"
jaundice, vomiting, HSM shortly after starting breastfeeding
CATARACTS and HEMOLYTIC ANEMIA via galactitol and G1P buildup
116
What are the renal manifestations of GALT deficiency (2)?
1. Hyperchloremic metabolic acidosis
| 2. Aminoaciduria
117
What infection does GALT deficiency predispose to?
E. coli sepsis
118
Mechanism of SPLENOMEGALY in PYRUVATE KINASE DEFICIENCY
hemolytic anemia > splenic removal of RBCs
reticuloendothelial cells in RED PULP of spleen undergo HYPERPLASIA to meet phagocytic demand
119
less common cause of PKU
additional issue, aside from Phe buildup?
BH4 (tetrahydrobiopterin) deficiency secondary to DIHYDROBIOPTERIN REDUCTASE deficiency
BH4 is a cofactor for Phe, Tyr and Trp hydroxylase
additional issue is SEROTONIN DEFIC.
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presentation of dihydrobiopterin reductase defic.
High Phe > disrupts neuron/glial dev.
Low serotonin > progressive neurodegeneration
dev delay
hypotonia
dystonia
seizures
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What hormonal abnormality can result from dihydrobiopterin reductase deficiency and why?
hyperprolactinemia
since BH4 is a cofactor for Tyr hydroxylase, DOPAMINE SYNTHESIS IS INHIBITED > no inhibition of PRL release by DA
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Vit D toxicity s/s
Hypercalcemia - weakness, constipation, confusion (ulcers longer term)
Polyuria/dipsia - impaired DCT urine concentration
Renal stones and BONE PAIN (excess actually promotes osteoclast activity)
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Porphyria Cutanea Tarda
enzyme def. (inheritance)
uroporphyrinogen decarboxylase
AD or acquired
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Porphyria Cutanea Tarda
susceptibility factors (5)
1. Alcohol
2. Smoking
3. Halogenated Hydrocarbons
4. Hepatitis C
5. HIV
just think partying and lots of Hs
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Porphyria Cutanea Tarda
main sx (1 + 2)
Tea-colored urine
Blistering cutaneous photosensitivity
Hyperpigmentation
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Acute Intermittent Porphyria
enzyme def and inheritance
PBG deaminase (aka uroporph I synthase)
AD
PBG and ALA build up
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AIP
sx (acronym)
what triggers it?
5 Ps
```
Painful ABDOMEN
Port wine URINE
Polyneuropathy
Psych issues
Precipitation by drugs (CYP450 inducers, alcohol, starvations)
```
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AIP
tx + MOA
HEMIN and GLUCOSE
both will inhibit ALA synthase
129
2 heme synth enzymes affected by Pb poisoning
substrates that accumulate
Ferrochelatase - accum. of protoporphyrin
ALA Dehydratase - accum. of ALA
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Pb poisoning
type of anemia caused + characteristics (2) + associations (2)
special exposures and sx in kids (1) ? adults (3) ?
MICROCYTIC anemia with BASOPHILIC STIPPLING in periph and RINGED SIDEROBLASTS in marrow
GI + Kidney disease
kids - lead paint exposure > retardation
adults - env exposure (batteries, ammo) > HA, memory loss, demyelination
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Pb poisoning
sx mnemonic (6)
LEAD - or actually LEEAAD
1. Lead Lines - on GINGIVAE ("Burton") and METAPHYSES (xray)
2. Encephalopathy + Erythrocyte stippling
3. Abdominal pain + Anemia
4. Drops - wrist + foot drop
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Pb poisoning
tx (3)
Dimercaprol and EDTA
Succimer in kids
(it "sucks" to be a kid with Pb poisoning)
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3 vitamin defic related to hyperhomocysteinuria
B6, B12 and folate
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Hormonal regulation of glucokinase
Insulin stimulates
Glucagon inhibits
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Zellweger syndrome
genes? defects?
AR issues with PEX genes for PEROXISOMES
(peroxisomes responsible for VLCFA beta-ox, alpha-oxidation, AA/ethanol breakdown, and synth of cholesterol, bile acids + "plasmalogens" - membrane p-lipids in brain)
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Zellweger Syndrome
pathophys
ABSENT PEROXISOMES cause lack of PLASMALOGENS (membrane phospholipids in CNS) > impaired neuron migration, position + brain development
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Zellweger Syndrome
s/s + presentaton
1. LARGE FONTANELS + MIDFACE HYPOPLASIA
2. Hepatomegaly, cryptorchidism
3. Hypotonia, seizures + early death
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What is the disorder of ALPHA-oxidation?
inheritance + buildup?
Refsum disease
AR disorder of PHYTANIC acid metabolism to PRISTANIC acid
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Refsum disease
s/s?
(5, think skin, eyes, bones, movement + acronym)
tx?
1. SCALY skin
2. CATARACTS + night blindness
3. ATAXIA
4. "RING" TOE (4th) is short
5. EPIPHYSEAL dysplasia
"SCARE"
tx with DIET and PLASMAPHARESIS
(remember it's an AR disorder of alpha oxidation with phytanic acid buildup)
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Adrenoleukodystrophy
inheritance + defect?
what builds up where (3 places)?
XR defect of beta-oxidation
LCFAs build up in...
1) ADRENAL glands ("adreno-")
2) WHITE matter of brain ("-leuko-")
3) TESTES
progressive > adrenal crisis, coma + death
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What would be seen in a gene that is altered by SLIPPED STRAND MISPAIRING?
an INCREASED NUMBER OF REPEATS
can be single or multiple nucleotide repeats
followed by the rest of the sequence being the same as before
142
Acetyl-CoA stimulates/activates which enzyme?
Inhibits which enzyme?
Explain.
stimulates PYRUVATE CARBOXYLASE - when acetyl-CoA is in excess (as in beta-oxidation), it is not needed for TCA cycle as much and is diverted to gluconeogenesis
inhibits PYRUVATE DEHYDROGENASE - pdh makes acetyl-CoA from pyruvate, so when its product is in excess its activity is not needed
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Citrate stimulates FA synthesis via acetyl-coa carboxylase...
how does it stimulate gluconeogenesis?
activation of FRUCTOSE-1,6-BISPHOSPHATASE
| reverses action of phosphofructokinase
