Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

*USMLE* > Biochem > Flashcards

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How long does glycogenolysis maintain blood glucose in the fasting state?

A

12-18 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

When does gluconeogenesis take over in maintenance of blood glucose during fasting?

A

after 12-18 hours, when glycogen stores are depleted

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which FOUR enzymes bypass irreversible glycolysis/TCA steps in gluconeogenesis?

A
  1. PYRUVATE CARBOXYLASE

(pyruvate > OAA (biotin)
OAA > Malate via MDH, then malate leaves mitoch and > OAA via cytosolic MDH)

  1. PEP Carboxykinase - (OAA > PEP)
  2. Fructose-1,6-bisphosphatase
  3. Glucose-6-phosphatase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

  1. GLYCOSYLASE - cleaves wrong base
  2. ENDONUCLEASE - cleaves 5’ end
  3. LYASE - cleaves 3’ sugar-P
  4. POLYMERASE - fills gap
  5. LIGASE - seals nick

“gel pill”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Retinoblastoma protein function

A

TUMOR SUPPRESSOR on chr. 13q14

hypophosphorylated > active > prevents G1 to S transition

hyperphosphorylated = opposite

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Alkaptonuria

inheritance? AA affected?

A

AR disorder of TYROSINE metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Alkaptonuria

s/s? what does built up metabolite bind?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

2 cause of congenital adrenal hyperplasia?

enzyme? s/s?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

which step of TCA cycle creates GTP?

A

Succinate thiokinase
(aka succinyl-coa synthetase)

Succinyl-CoA > succinate (GDP > GTP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Other than transphosphorylation of ADP to ATP…

what can GTP formed in the TCA do?

A

is used by specific GTP-hydrolyzing enzymes like…

PEP carboxykinase (gluconeogenesis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

pentose phosphate pathway. IC location?

A

cytosol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

FA synthesis pathway. IC location?

A

cytosol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

2 thiamine dependent steps of TCA

what other paths are thiamine-dependent? which enzymes? (2)

A

pyruvate dehydrogenase complex

alpha keto glutarate DH complex

PP pathway - TRANSKETOLASE needs thiamine

BCKA Dehydrogenase - deficient in maple syrup urine disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

irreversible part of pentose phosphate pathway makes what?

for what processes?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

reversible part of PPP makes what?

for what 2 processes?

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

what is the metabolic advantage of the REVERSIBILITY of the non-oxidative steps of the PPP?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

DNA Polymerase I activity

prokaryotes

A

unique activity is 5’-3’ EXONUCLEASE which functions to REMOVE RNA PRIMER

also has 3’-5’ exonuclease, as do ALL prokaryotic DNA polymerases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

DNA Polymerase III activity

prokaryotes

A

5’ to 3’ polymerase
3’ to 5’ exonuclease

main polymerase of prokaryotic replication

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

DNA gyrase

other name, function, inhibitor

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Inclusion Cell Disease

inheritance? defect?

A

AR inheritance

defect of lysosomal storage

defective PHOSPHOTRANSFERASE enzyme can not phosphorylate MANNOSE residues on glycoproteins in Golgi headed to lysosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Inclusion Cell Disease

s/s?

think eyes, msk system, RES

A 
failure to thrive + dev delay
COARSE FACIAL features
CORNEAL CLOUDING
HSmegaly
restricted JOINT MOBILITY
GINGIVAL hyperplasia
CLAW HAND deformity
Kyphoscoliosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Path of glucagon’s effect on glycogen metabolism

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

how can muscle “glycogen phosphorylase b” have the same action as “glycogen phosphorylase a” (the active P-ated form)?

A

allosteric modulation by AMP

changes it from tense to relaxed, functional state

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Hunter syndrome

inheritance? enzyme? accumulation

A

mucopolysaccharidosis type II

XR inheritance

lack of iduronate-2-sulfatase

heparan and dermatan sulfate (GAGs) accumulate in all tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Hunter syndrome

s/s? dx?

A 
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

which ribosomal enzyme forms peptide bonds btwn AAs?

A

peptidyl transferase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

what tissues have both ALDOSE REDUCTASE and SORBITOL DEHYDROGENASE activity?

A

they “LOSe” sorbitol

liver
ovaries
seminal vesicles (sem ves make the fructose that goes into semen)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

what tissues have only aldose reductase activity?

A

sorbitol is LRKN in these tissues

lens, retina, kidney, neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

what is the first enzyme in gluconeogenesis?

what metabolic intermediate stimulates it?
and what does this intermediate inhibit?

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

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?

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Main ALLOSTERIC ACTIVATOR of PYRUVATE KINASE

A

F-1,6-BP

“feedforward” stimulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Main COVALENT MODIFIERS of PYRUVATE KINASE

ie, things that cause phosphorylation / dephosphorylation (hint: molecules that have lots of downstream cellular effects via surface receptors)

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

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.

A
  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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Main regulator of phosphofructokinase-1 and its gluconeogenetic counterpart enzyme?

How does regulation work?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What two enzymes does B12 act as a cofactor for?

Deficiency results in buildup of what? (2)

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Erythrocyte TRANSKETOLASE activity is reduced in deficiency of what?

which causes what?

A

Vitamin B1 - Thiamine

deficiency causes Wernicke-Korsakoff and BeriBeri

(transketolase is an HMP shunt enzyme)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

in the WELL-FED STATE, what citrate cycle enzyme is inhibited and why? what is the result?

A

ISOCITRATE DEHYDROGENASE is inhibited by high levels of ATP

this causes a buildup of CITRATE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

how does citrate leave the citrate cycle during the well-fed state, where does it go + what does it do?

A

CITRATE SHUTTLE transfers it from mitochondria to CYTOSOL where it is cleaved by ATP CITRATE LYASE to form ACETYL-CoA for FA SYNTH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

what two things cause upregulation of the rate-limiting step of fatty acid synthesis?

and what does this initial step create?

A

CITRATE and INSULIN both upregulate ACETYL-CoA CARBOXYLASE

ACC creates MALONYL-CoA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

After formation of malonyl-CoA by ACC how are fatty acids synthesized? Enzyme etc

A

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
Q

How does fatty acid synthesis regulate fatty acid beta-oxidation?

A

MALONYL-CoA formed by ACC has an inhibitory effect on CARNITINE ACYLTRANSFERASE, which prevents movement of fatty acids into the mitochondrial matrix

60
Q

WHAT removes introns from mRNA and HOW CAN IT RECOGNIZE WHERE to remove them from?

A

“Spliceosomes” - complexes of snRNPs and other proteins

introns contain two signals for splicing:
5’ splice site - GU
3’ splice site - AG

61
Q

what are the repeats in telomeres?

added by what enzyme with what kind of action?

A

TTAGGG repeats

added by TELOMERASE - an RNA-dependent DNA polymerase

62
Q

Vitamin B1 deficiency in NON-ALCOHOLIC adults

2 types - what are they?

A

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
Q

Vitamin B1 deficiency in babies

A

infantile beriberi - presents at 2-3 months

a “fulminant cardiac syndrome” with cardiomegaly, tachycardia, cyanosis, dyspnea and vomiting

64
Q

Fabry

(inheritance, deficiency, accumulation, sx)

(sx have an early triad + late fx)

A

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
Q

Tay-Sachs

(inheritance, deficiency, accumulation, sx, special histo)

(differentiation from other similar disease)

A

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
Q

Gaucher

inheritance, deficiency, accumulation, sx and HISTO

A

AR - #1 sphingolipidosis

glucocerebrosidase (tx with recombinant)

glucocerebroside

HSmegaly
pancytopenia
bone pain/osteopenia/femur avascular necrosis

Gaucher cells - crumpled paper lipid laden macros

67
Q

Niemann-Pick

(inheritance, deficiency, accumulation, sx and HISTO)

(differentiation)

A

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
Q

Krabbe

inheritance, deficiency, accumulation, sx and HISTO

A

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
Q

Metachromatic Leukodystrophy

inheritance, deficiency, accumulation, sx

A

AR

arylsulfatase A

cerebroside sulfate

CNS / PNS demyelination (LEUKOdystrophy) with…
ataxia
dementia

70
Q

3 main processes that occur to precursor mRNA (heterogenous nuclear RNA; hnRNA) before it leaves the nucleus

A
  1. 5’-methylguanosine capping
  2. 3’ polyadenylation
  3. intron splicing
71
Q

2 main processes that mature mRNA might undergo after it leaves the nucleus

A
  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
Q

Polyadenylation

what enzyme? what signal sequence on preMRNA? how many adenines?

A

POLYADENYLATE POLYMERASE complex recognizes an AAUAAA sequence, cleaves downstream and adds 20-250 adenines

73
Q

Capping of preMRNA

2 enzymes

A

GUANYLYLTRANSFERASE - adds 5’ GTP

GUANINE-7-METHYLTRANSFERASE - methylates

74
Q

What are c-Jun and c-FOS?

A

nuclear transcription factors

bind DNA via a leucine zipper motif

75
Q

Hereditary Orotic Aciduria

inheritance? enzyme?

A

AR inheritance

UMP synthase (enzyme in de novo pyrimidine synthesis)

76
Q

Hereditary Orotic Aciduria

3 clinical signs

A
  1. Mental + physical developmental delay
  2. Megaloblastic anemia
  3. Elevated urinary orotic acid
77
Q

Hereditary Orotic Aciduria

Differential dx?

Tx?

A

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
Q

what 2 properties of ELASTIN give it is elasticity?

A
  1. high content of NONPOLAR amino acids (glycine, alanine, valine)
  2. DESMOSINE CROSS-LINKS - between deaminated Lysines (via lysyl oxidase + Cu) on neighboring
79
Q

BCKA Dehydrogenase

metabolizes Val, Leu and Ile (BCAAs) into what?

2 products

A

Leu becomes ACETYL-CoA ( > TCA cycle)

Val, Ile become PROPIONYL-CoA ( > methylmalonyl-Coa > Succinyl-CoA > TCA cycle)

80
Q

Maple Syrup Urine Disease / BCKA DH defic.

S/S? Consequence if untreated?

A

Neurotoxicity - seizures, lethargy, irritability, poor feeding

BRAIN SWELLING can result in death

81
Q

Deficiency other than Phe hydroxylase that can result in PKU?

A

Tetrahydrobiopterin - a cofactor for Phe hydroxylase

82
Q

Vitamin B6 / pyridoxine

involved in what 4 biochem processes?

A
  1. Transamination - AAs
  2. Decarboxylation - AAs
  3. Heme synth
  4. NT synth
83
Q

Arginase catalyzes what reaction?

A

formation of UREA and ORNITHINE from arginine

84
Q

Arginase Deficiency

presentation (3)?
labs (one positive and one negative test)?
tx (2)?

A
  • 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
Q

What two urea cycle disorders result in buildup of orotic acid? Why?

A
  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
Q

When is blood glucose maintained primarily by hepatic glycogenolysis?

A

from 4-16 hours after last meal

over this time glycogenolysis slowly decreases and gluconeogenesis slowly increases

87
Q

When is blood glucose primarily maintained by hepatic gluconeogenesis?

A

about 16-48 hours after last meal

glycogenolysis wanes starting at 16 hours

88
Q

When is blood glucose maintained by BOTH HEPATIC and RENAL gluconeogenesis?

A

from 2 days after last meal

up to ~24 days brain uses mostly glucose, partly ketones

after ~24 days brain uses mostly ketones

89
Q

Long-chain acyl-CoA DH deficiency

s/s?

A

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
Q

Long-chain acyl-CoA DH deficiency

serum (3) + urine changes (2)?

tx?

A

serum - low glucose, ketones + carnitine

urine - low ketones and HIGH DICARBOXYLIC ACIDS

glucose and MCTs for tx

91
Q

an EM img of the cell of a patient with a DEFECT IN VESICLE TRAFFICKING TO GOLGI would show what?

A

Dilated RER

proteins are not properly trafficked on past the RER so accumulate there

92
Q

What TWO TYPES OF SACCHARIDES on which THREE AMINO ACIDS are modified by the Golgi for trafficking?

A

N-oligosaccharides on Asparagine

O-oligosaccharides on Serine, Threonine

93
Q

What molecule is present on proteins to direct them to lysosomes?

A

mannose-6-phosphate

protein is glycosylated with mannose, then phosphorylated by N-acetylglucosaminyl-1-phosphotransferase (defective in I-cell disease)

94
Q

What molecule helps proteins target the RER from ribosomes?

A

SRP - signal recognition particle

a ribonucleoprotein abundant in cytosol

if absent proteins accumulate in cytosol

95
Q

What is the function of an endosome?

A

“sorting center” directs stuff from out of cell or Golgi to either lysosomes or back to membrane/Golgi

96
Q

What are the two VESICULAR TRAFFICKING PROTEINS for anterograde/retrograde Golgi transport?

A

COP-II - anterograde; from ER to cis-Golgi

COP-I - retrograde; from cis-Golgi to ER

“two steps forward, one step back”

97
Q

What is the VESICULAR TRAFFICKING PROTEIN for movement from the trans-Golgi to lysosomes/plasma membrane?

A

Clathrin

98
Q

What biochemical process is responsible for muscle protein wasting in non-use atrophy?

A

polyubiquitination

99
Q

What is the more severe mucopolysaccharidosis?

enzyme? inheritance? s/s?

A

Hurler syndrome - AR alpha-L-iduronidase

heparan + dermatan sulfate accumulate

  • Dev delay
  • Gargoylism
  • Airway obstruction
  • Corneal clouding
  • HSM

(DGACH)

100
Q

What is the less severe mucopolysaccharidosis?

enzyme? inheritance? s/s?

A

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
Q

vitamin deficiencies in CF patient

what kind?

A

fat-soluble due to exocrine lipase insufficiency

A, D, E, K

102
Q

Vitamin E excess

what two sx?

A
  1. ENTEROCOLITIS in infants

2. Enhanced ANTICOAGULATION with WARFARIN - due to altered vit K metabolism

103
Q

Vitamin E deficiency

s/s?

A
  • 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
Q

What is an open reading frame?

A

a continuous stretch of codons that contains a start codon and a stop codon

105
Q

The PRESENCE OF WHAT can allow an mRNA lacking a 5’-MG cap to still be translated?

A

an INTERNAL RIBOSOME ENTRY SITE

5’ caps regulate: 1) nuclear export, 2) degradation prevention, 3) translation promotion, and 4) 5’ proximal intron excision

106
Q

What in the ETC does carbon monoxide inhibit?

it has lots of names, which is super stupid

A

cytochrome c OXIDASE
aka complex IV
aka cytochrome a-a3

(so note this is NOT cytochrome C itself, but cyt C oxidase)

107
Q

RNA Polymerase I in eukaryotes makes what?

A

ribosomal RNA

18S, 5.8S and 28S

(all but one rRNA made by RNA pol I … 5S made by RNA pol III)

108
Q

RNA Polymerase II in eukaryotes makes what? (3)

A
  1. mRNA
  2. snRNA - splicing + transcription regulation
  3. miRNA - gene silencing (translation arrest/mRNA degradation)
109
Q

RNA polymerase III in eukaryotes makes what? (2)

A
  1. tRNA

2. the 5s ribosomal RNA

110
Q

3 important intermediates yielded by beta-oxidation

A

1) FADH2 and 2) NADH, both for ATP production in etc

3) acetyl-CoA for use in TCA cycle or ketogenesis

111
Q

Difference in timeline of ketone body use in adults vs. children

A

adults - require 1-2 days fasting before ketogenesis is significant

kids - lower glucose reserves; ketogenesis begins in 8-10 hours

112
Q

Medium-Chain Acyl-CoA DH deficiency

S/S (6)?

what accumulates?

A

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
Q

Primary Carnitine Deficiency

S/s
labs
complication (1)

A

“hypoketotic hypoglycemia” with WEAKNESS and HYPOTONIA

toxic accumulation of LCFAs

MUSCLE TRIGLYCERIDES are elevated

can cause CARDIOMYOPATHY

114
Q

Galactokinase deficiency - s/s

A

cataracts and (rarely) pseudotumor cerebri

due to galactitol buildup

115
Q

Galactose-1-phosphate uridyl transferase (GALT) deficiency

s/s

A

“Galactosemia”

jaundice, vomiting, HSM shortly after starting breastfeeding

CATARACTS and HEMOLYTIC ANEMIA via galactitol and G1P buildup

116
Q

What are the renal manifestations of GALT deficiency (2)?

A
  1. Hyperchloremic metabolic acidosis

2. Aminoaciduria

117
Q

What infection does GALT deficiency predispose to?

A

E. coli sepsis

118
Q

Mechanism of SPLENOMEGALY in PYRUVATE KINASE DEFICIENCY

A

hemolytic anemia > splenic removal of RBCs

reticuloendothelial cells in RED PULP of spleen undergo HYPERPLASIA to meet phagocytic demand

119
Q

less common cause of PKU

additional issue, aside from Phe buildup?

A

BH4 (tetrahydrobiopterin) deficiency secondary to DIHYDROBIOPTERIN REDUCTASE deficiency

BH4 is a cofactor for Phe, Tyr and Trp hydroxylase

additional issue is SEROTONIN DEFIC.

120
Q

presentation of dihydrobiopterin reductase defic.

A

High Phe > disrupts neuron/glial dev.
Low serotonin > progressive neurodegeneration

dev delay
hypotonia
dystonia
seizures

121
Q

What hormonal abnormality can result from dihydrobiopterin reductase deficiency and why?

A

hyperprolactinemia

since BH4 is a cofactor for Tyr hydroxylase, DOPAMINE SYNTHESIS IS INHIBITED > no inhibition of PRL release by DA

122
Q

Vit D toxicity s/s

A

Hypercalcemia - weakness, constipation, confusion (ulcers longer term)

Polyuria/dipsia - impaired DCT urine concentration

Renal stones and BONE PAIN (excess actually promotes osteoclast activity)

123
Q

Porphyria Cutanea Tarda

enzyme def. (inheritance)

A

uroporphyrinogen decarboxylase

AD or acquired

124
Q

Porphyria Cutanea Tarda

susceptibility factors (5)

A
  1. Alcohol
  2. Smoking
  3. Halogenated Hydrocarbons
  4. Hepatitis C
  5. HIV

just think partying and lots of Hs

125
Q

Porphyria Cutanea Tarda

main sx (1 + 2)

A

Tea-colored urine

Blistering cutaneous photosensitivity
Hyperpigmentation

126
Q

Acute Intermittent Porphyria

enzyme def and inheritance

A

PBG deaminase (aka uroporph I synthase)

AD

PBG and ALA build up

127
Q

AIP

sx (acronym)

what triggers it?

A

5 Ps

Painful ABDOMEN
Port wine URINE
Polyneuropathy
Psych issues
Precipitation by drugs (CYP450 inducers, alcohol, starvations)
128
Q

AIP

tx + MOA

A

HEMIN and GLUCOSE

both will inhibit ALA synthase

129
Q

2 heme synth enzymes affected by Pb poisoning

substrates that accumulate

A

Ferrochelatase - accum. of protoporphyrin

ALA Dehydratase - accum. of ALA

130
Q

Pb poisoning

type of anemia caused + characteristics (2) + associations (2)

special exposures and sx in kids (1) ? adults (3) ?

A

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

131
Q

Pb poisoning

sx mnemonic (6)

A

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
132
Q

Pb poisoning

tx (3)

A

Dimercaprol and EDTA

Succimer in kids

(it “sucks” to be a kid with Pb poisoning)

133
Q

3 vitamin defic related to hyperhomocysteinuria

A

B6, B12 and folate

134
Q

Hormonal regulation of glucokinase

A

Insulin stimulates

Glucagon inhibits

135
Q

Zellweger syndrome

genes? defects?

A

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)

136
Q

Zellweger Syndrome

pathophys

A

ABSENT PEROXISOMES cause lack of PLASMALOGENS (membrane phospholipids in CNS) > impaired neuron migration, position + brain development

137
Q

Zellweger Syndrome

s/s + presentaton

A
  1. LARGE FONTANELS + MIDFACE HYPOPLASIA
  2. Hepatomegaly, cryptorchidism
  3. Hypotonia, seizures + early death
138
Q

What is the disorder of ALPHA-oxidation?

inheritance + buildup?

A

Refsum disease

AR disorder of PHYTANIC acid metabolism to PRISTANIC acid

139
Q

Refsum disease

s/s?

(5, think skin, eyes, bones, movement + acronym)

tx?

A
  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)

140
Q

Adrenoleukodystrophy

inheritance + defect?

what builds up where (3 places)?

A

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

141
Q

What would be seen in a gene that is altered by SLIPPED STRAND MISPAIRING?

A

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
Q

Acetyl-CoA stimulates/activates which enzyme?

Inhibits which enzyme?

Explain.

A

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

143
Q

Citrate stimulates FA synthesis via acetyl-coa carboxylase…

how does it stimulate gluconeogenesis?

A

activation of FRUCTOSE-1,6-BISPHOSPHATASE

reverses action of phosphofructokinase

*USMLE* (28 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions