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Flashcards in Biochem Phys Deck (356):
1

link between glycolysis and TCA cycle

Pyruvate Dehydrogenase

2

nuclear localization signal?

(3)

marks a protein to enter the nucleus made of proline, lysine and arginine

3

vimentin

Associate w?

intermediate filament in connective tissue

sarcomas

4

desmin

associate w?

intermediate filament in muscle

associate w/ myosarcoma- leiomyosarcomas and rhadbomyosarcoma

5

cytokeratin

associate w/

intermediate filament in epithelial cells

Associate w/ carcinoma

6

GFAP

associate w/

intermediate filament in glial cells

Associate w/ astrocytoma and gliobastoma

7

Neurofilaments

associate w/

intermediate filament in neurons

Associate w/ neuroblastoma and primitive neuroectoderma tumors

8

Nuclear lamina ABC

associate w?

intermediate filaments making up the nuclear envelope

associate w/ mutations -> progeria (old age)
and muscular dstrophy

9

Microfilaments function?

actin and myosin

- cellular motility

10

Microtubule function

movement - cilia, flagella and mitotic spindle

11

Intermediate filaments function

cellular skeleton - differs w/ each ell used to ID cancer etiology

12

retrograde movement on microtubule

dynein

13

anterograde movement on microtubule

kinesin

14

Tyrosine Kinase receptor Examples and how composition (4)

PDG- single pass - transmembrane
Growth factor receptors - single pass trash membrane

Insuling and IGF -1 -
-2alpha bound extras cell and 2 beta w/ tyrosine activity

15

Improper clathrin and adapt in leads to

inability for receptor binding lwading to endocytosis-> can't bring in

- recycled

16

Phosphatydalinositol?

enzyme that acts on it?

cell membrane phospholipid that leads to AA

Phosolipase A2

17

Drug blocking leukotrien production and MOZ

Zilueton

blocks lipoxygenase

18

Of the leukotriene receptor antagonist, which is best to give to a kid

Montelukast

Not as much Zafirlukast

19

Action of Leukotrienes (2)

Chemotaxis of PMN- LTB4
Increases bronchial tone - LTC4 and LTD4

20

Action of prostacyclin (4)

PGI2
Decreases uterine contraction
Decreases platelet aggregation
Decreases brachial tone
Decreases vascular tone

21

Action of prostaglandins (4)

PGE2 and PGF2A
Increases uterine contraction
Increases gastric mucosa production
Decreases vascular tone (KEEEEPS open)
Decreases bronchial tone

22

Action of thromboxane (3)

TxA2
Increases platelet aggregation
increases bronchial tone
Increases vascular tone
(opposite of PGI2)

23

APAP - acetaminophen's action vs other COX inhibitors

Inactivated peripherally thus no anti inflammatory or anti platelet action

24

BCL-2

major anti apoptotic regulator of Mitochondrial permeability

25

BAX

major pro apoptotic regulator of mitochondrial permeability

26

Cytochrome C

Released from mitochondrial membrane for intrinsic apoptosis

27

3 mech of apoptosis

Ultimat goal

- caspase activation
1. intrinsic - mitochondrial
2. extrinsic
- FAS-R (CD95) and TNF-R
- T killer cells
3. p53 recognizing irreversible DNA damage

28

T killer cells mech of apoptosis(2)

- Perforin pops a hole
-Granzyme B leads to caspase activation

29

ligand mediated extrinic pathway of apoptosis

FAS-r (CD95) or TNF w/ TNF alpha activated ->caspase actiatopn

30

coagulative necrosis
-location (3)
-description

heart, liver, lungs

gelatinous low O2 levels-> loss of necucli w/ preserved cell form

31

liquefactive necrosis
-location (3)
-description (3)

brain, pleural effusion, bacterial abscess

digestion/hyldolases from microorg and PMNs

32

Caseous necrosis
-location/causes (2)
description

TB and fungi

combine of liquefactive and coagulative

33

Fatty necrosis
-location (1)
- Description

peripancreatic fat w/ lipase release

-saponification of fat (Calcification)

34

Fibrinoid necrosis
-location (1)
-description/causes

blood vessels

arteritis/autoimmune and malignant HTN

35

Gangrenous necrosis
Types (2)

dry - ischemia coagulative - arteriole occlusion of toes/fingers

wet - bacteria

36

Reversible cell injury characterized by

cellular swelling - noATP -> impaired Na/K

37

Irreversible change to a cell (5)

Nuclear changes
-pyknosis(shrink), karylysis(loss of), karyorrhexis(fragment)
Ca influx
plasma membrane change

lysosomoal rupture
Mito permeability

38

Superoxide dismutase

O2 free radical -> H2O2

39

Catalase

H2O2 -> O2 and H2O

40

Glutathione peroxidase

Also protects from ROS

41

red infarct

Reprofusion therapy -> increased ROS damage, O2 comes in (why we have stroke and MI timing on tPA)

- collateral circulation (liver, lung, intestine) or reprofusion therapy seen

42

Pale infarct

solid tissue seen w/ not revascularizing

43

Chromatin is made of

Histones
-8 binding to DNA H2A, H2B, H3, H4
-H1 connecting the two

DNA

Each bundle is a nucleosome

44

What binds DNA to the Histones (3 components)

DNA is negatively charged w/ phosphate

Histones are positively charged w/ Lysine and Arginine

45

Purines are get their N and C from 5 sources

Aspartate -N
Glutamine -N
Glycine -C
CO2- C
THF - C

46

Pyrimidine gets their N and C from 4 sources

Carbamoyl phosphate
-CO2 - C
-Glutamine -N
-ATP - energy

Aspartate - C

47

Which bond is stronger G-C or A-t

G-C due to 3 bonds instead of 2

48

Whats the difference between Cytosine and uracil?

Cytosine is uracil that has been deaminated

Cytosine is in DNA
Uracil is in RNA

49

Purine vs Pyrimidine synthesis

Pyrimidine you make a temporary base (orotic acid) and then add phosphate and sugar to it w/ PRPP and then modify

Purines you make the phosphosphate ribose sugar first w/ PRPP and then you add the base

50

Enzymes in pyrimidine synthesis enzymes to know (4)

Carbamoyl Phosphate Syntase II(rate limiter)

ribonucleuotide reductase (hydroxyurea)
-UDP-> dUDP

Thymidylate syntase (5-FU)
-dUMP ->dTMP

Dihydropholate reductase (MTX/TMP)
DHF->THF (regeneration)

51

Enzymes to know in Purine synthesis (2)

Glutamine PRPP amidotransferase (rate limiter) (6 mercaptopurine

IMP dehydrogenase (mycophenolate)
-IMP-> GMP

remember easier pathway, though has more ingredients

52

inhibits ribonucleotide reductase

hydroxyurea
UDP->dUDP

53

inhibits dihydrofolate reductase (2)

Methrotexate - eukaryotes
Trimethoprim - prokaryotes

Regenerates DHF -> THF

54

Inhibits thymidylate syntase

5 Fluroracil
dUMP ->dTMP

55

Inhibits idenosone monophosphate dehydrogenase

mycophenalate

IMP -> GMP

56

Inhibits PRPP amidotransferase

6 mercaptopurine

1st step in making a purine with the ribose phosphate transfer

57

2 types of carbamoyl phosphate syntetase
- location
-Pathway
-N sources

CPS-1
-mitcochondria
- Urea Cycle
- ammonia

CPS -2
-Cytosol
- Pyrimidine synthesis
-Glutamine

58

megaloblastic anemia that does not improve w. folate and B12

UMP syntase deficiency (pyrimidine synthesis pathway0

- > orotic aciduria

59

patient presents w/ orotic acid in their urine w/o hyper ammonia

presents as?(2)

defect in UMP synthase in the pyrimidine synthesis -> build of orotic acid
- can't convert orotic acid into UMP

FTT
Megaloblastic anemia

Rx w/ uridine administration

VS - OTC deficiency in the urea cycle (Orotic acid in urine and hyper ammonia)

60

Deficiency in UMP synthesis presents as

FTT
Megaloblastic anemia
orotic aciduria w/o hyperammonia

Rx w/ uridine administration

61

Defect in HGPRT leads to ?

Presentation (5)

Lesch Nyhan, defect in purine pathway and can't recover guanine and hypoxanthine

both become xanthine -> xanthine oxidase enzyme converts to a lot of uric acid

aggression
retardation
Gout
self mutilation
choreathetosis - writhing movements

62

Adenosine deaminase deficiency leads to

Presents as

SCID (diarrhea, recurrent infection, FTT)

Defect in purine breakdown of adenosine -> Inosine in the pathway

Build up of adenosine is toxic to lymphocytes due to decreased DNA synthesis

Auto recessive

63

DNA polymerase alpha

eukaryotic

makes its own primer and builds the lagging strand

~ DNA polymerase III in prokaryotes - except delta makes the leading

64

DNA polymerase delta

eukaryotic

makes the leading strand of DNA

~ DNA polymerase III in prokaryotes - except alpha makes the lagging

65

DNA polymerase beta

eukaryotic

DNA repair

~DNA polymerase III exonuclease function of proofreading

66

DNA polymerase gamma

makes mitochondria DNA

67

Silent mutation

same amino acid despite different base pair

3 BP often a wobble

68

missense mutation

mutation in which the wrong AA is coded leading to dif structure or funciton

69

nonsense mutation

mutation in which the stop codon is made early -

70

Pyrimidine dimer

2 pyrimidines on the same strand of DNA get covalently bonded together

UV light damage -> thymine Thymine binding on the same strand

71

Nucleotide excision repair steps

Damage in SS results in bulky helix
1. endonuclease - specific
2. DNA polymerase fills
3. ligase seals

Damaged in xeroderma pigmentosa; auto recessive

72

Mismatch repair steps

Newly synthesized DNA is recognized as mismatch and removed - Gaps resealed

Damaged in HNPCC

73

Base excision Repair steps

damage to a specific BP, important in spontaneous/toxic deamination

1. glycosylases recognize damage
2. endonucleases remove
3. DNA polymerase fills
4. Ligase reseals

74

Nonhomologous end joining

dsDNA repair where 2 ends of DNA fragments are put back together after a clean break

No requirement for homology

Mutated in ataxia telangiectasia

75

Mutated in xeroderma pigmentosa

auto recessive

Nucleotide excision repair

76

Mutated in hereditary nonpolyposis colorectal cancer

mismatch repair

77

Mutated in ataxia telangiectasia

non homologous end joining

- sensitivity to radiation

78

Mutated in BRCA 1 and 2

dsDNA repair mech

79

DNA is always written

5'-3'

even when copying down an alternate strand****
- unless otherwise labeled

80

AUG

Start codon
Methionine

81

UGA, UAA, UAG

stop codons

82

Eukatyote RNA polymerases (3)

RNA polymerase I - rRNA
RNA polymerase II - mRNA
RNA polymerase III - tRNA

no proofreading

83

alpha amanitin

mushroom toxin that inhibits RNA polymerase II -> hepatotoxicity

84

Prokaryote RNA polymerase

RNA polymerase

Does what takes eukaryotes 3 polymerases to do

85

Operon is composed of(3)

on the DNA -> RNA

structural genes that are transcribed

promotor region

all reglulatory genes

86

Transcription factors bind to (3)

proteins that must bind to promoter regions to allow transcription

Always located upstream
- CCAAT box 75 bp up
-hodgness/TATA box 25 bp up
-pribnow/TATAAT box 10 bp up

87

Operator regions in transcription (2)

located?

proteins bind to these regions which are located in areas between the promoter region and structural gene

either binds to a repressor (ex lac operon)

or inducer (starts)

88

Response elements in transcriptions(2)

located?

Enhancer regions that up regulate the RATE of transcription

Repressor regions that down regulate the RATE of transcription

May be located anywhere on the DNA

89

Structural motifs that interact w/ DNA(4)

Helix loop helix
helix turn helix
zinc finger motif
leucine zipper protein

90

Termination of prokaryotic transcription (2)

rho factor - uses RNA dependent ATPase to put energy in the situation and then turns off

GC rich region forms a tight hairpin loop in the RNA that stresses the system and subsequent weak RNA bonds (uracil rich) fall off

91

Lac operon regulation of beta galactosidase

TF CAP is around in the presence of lactose

lac repressor is absent w/out glucose around

92

hetergeneous nuclear RNA is transformed how? (3)

becomes mRNA through

1. 5' capping (s adenosyl methinine)

2. polyadenilation on 3' (poly a polymerase using polyadenilation signal, no template)

3. splices out introns (spliceosome)

93

Enzyme responsible for charging tRNA

What signals location?

Aminoacyl tRNA synthetase charges on the 3' CCA

uses a little ATP

94

Ribosomes are made of and where? (3)

proteins and tRNA - nucleoplasm

rRNA - nucleolus

95

Steps of protein synths (3)

initiation
- Needs IF factors and assembles 30S and 50S
-GTP is used

Elongation
- more aminoacyl tRNA binds to the A site
- ribozyme (peptidyletransferase) catalyzes the transfer of the growing peptide chain
-Translocation allows more tRNA to come in

termination
- Runs into a AUG and release factor breaks apart the complex

96

Sites of action in protein synthesis (3)

A - Aminoacyl tRNA incoming binds here
P - accommodates the growing peptide
E - empty and allows exit to the uncharged tRNA

97

Elongation factors in prokaryotes and eukaryotes

function to help tRNA bind and transpeptidase

E2F in euk
G in pro

98

Antibiotics that bind to 30s and MOA (2)

Aminoglycosides - bind early and prevent initiation complex formation

Tetracyclines - bind later and prevent incoming aminoacyl tRNA from binding to the A site

99

Antibiotics that bind to the 50s site and MOA (6)

Macrolides
clindamycin
streptogramins
lincomycin

-all prevent translocation

linozolid - prevent initiation complex from forming

Chloramphenicol - prevent transpeptidase action at 23s

100

codominance

both alleles contribute to the phenotype

101

variable expressivity

means that the SEVARITY of the phenotype varies amongst individuals with a common genotype - ex tuberous sclerosis

Differs from incomplete penetrance in whether or not the EXPRESSION of a phenotype occurs for a common genotype

102

incomplete penetrance

whether or not the EXPRESSION of a phenotype occurs for a common genotype

vs variable expressivity which means the SEVARITY of the phenotype varies amongst individuals with a common genotype

103

Pleiotropy

the phenotypic expression of a gene mutation affects a lot systems

ex PKU

104

Imprinting

the defferences in gene expression depends on the whether the mutation is of maternal or paternal origin

Prader will and Angelman

105

Mosaicism

when the cell express differed genetic makeup within an organism

due to post fertilization loss or change of genetic info during mitosis

106

locus heterogeneity

many mutations of genotype lead to a common phenotype being expressed

ex - albinisim, Marfans-MEN2B- Homocystinuria are all related

107

Prader willi syndrome due to

Presentation(4)

loss of the paternal allele on chromosome 15 (maternal allele already imprinted and silenced)

hyperphagia -> obesity
mental retardation
hypogonadism -> osteoperosis and delayed menarche
hypotonia and facial abnormalities

108

Angelman syndrome due to

Presentation(3)

loss of the maternal allele on chromosome 15 (paternal allele already imprinted and silenced)

Happy puppet
-mental challenges
-ataxia
-inappropriate laughter

109

Hardy weinberg equations (4)

p + q = 1

p squared + 2pq + q squared = 1

p squared = frequency of allele of p
q squared = frequency of allele of q

110

PCR steps (3)

goal is to create a lot of copies of a DNA to mess around with

1. Denature- heat gently separate out the DNA strands

2. Annealing -add DNA primers to set up DNA polymerases to copy target genes

3. Elongation - heat stable DNA polymerase replicate target gene

repeat

111

DNA gel electrophoresis basics

separates negatively charged DNA by size
+ charge opposite of the wells with a negative charge

the smallest DNA fragments travel the farthest
Can be compared to known DNA wells run alonside

112

Protein gel electrophoresis basics

similar to DNA electrophoresis except have both + and - charges in proteins

Well is put in the middle and opposite charges are placed on either side

113

Southern blotting

Way to visualize your DNA sample using a known radiographic DNA probe that anneals to your target after it has been soaked in a denaturant that separates out the strands

after gel electrophoresis

114

Northern blotting

way to visualize your RNA sample using a known radiographic DNA probe that anneals to your target

after gel electrophoresis

115

Western blotting

way to visualize your protein sample using a known radiographic antibody probe that anneals to your target

after gel electrophoresis

116

southwestern blotting

way to visualize DNA binding proteins using a radiographic oligonucleotide sequence which the desired protein can bind to

117

Indirect ELISA vs Direct ELISA

indirect ELISA uses a known antigen and tests a patients serum for the presence of an Antibody -> color change
-ex HIV

direct ELISA uses a known antigen and tests for the presence of an Antigen in the patients serum -> color change

118

FISH mech

uses fluorescent DNA or RNA probes that bind to specific gene sequences on chromosomes.

Probes that bind mean that the known gene is present

119

Cloning mech of cDNA (4)

1. find a mRNA of interest and isolate
2. use a reverse transcriptase to create an cDNA copy
3. insert the cDNA fragment in a bacterial plasmid to replicate (antibiotics selective for those that do not take up the cDNA)
4. Those that survive have the cDNA (~gene minus the introns)

120

Karyotyping

looking at chromosomes that have been organized according to morphology, size, arm length and banding pattern

Something you visually look at for gross chromosomal deformity (chromosomal imbalances)

121

Aerobic metabolism glucose using the malate aspartate shuttle occurs where? Produces how much ATP

heart and liver and kidney

32 ATP

122

Aerobic metabolism of glucose using the glycerol 3 phosphate shuttles

Produces how much ATP?

brain and muscle

30 ATP

123

Glycolytic enzyme deficiency clinical consequence?

What enzyme is deficient?

Hemolytic anemia

Usually pyruvate kinase

124

Phosphorylation of glucose to glucose 6 phosphate is done by (2)?

Where is each one and associated Km and Vmax

hexokinase is ubiquitous
- High affinity (low Km) and low capacity (low Vmax)

glucokinase is in the liver and beta islet cells
- low affinity (high Km) and high capacity (high Vmax)
-induced by insulin

125

What is the rate limiting enzyme of glycolysis?

What can up regulate its function(2)

What can down regulate it (2)

Phosphofructokinase 1 (PFK 1)

AMP and Fructose 2,6 bis-phosphate (+)

ATP and citrate (-)

126

What is the most common enzyme deficiency in glycolysis

What up regulates its function? (1)

What down regulates? (2)

Pyruvate kinase
--( Phosphoenolpyruvate (PEP)-> pyruvate)

(+) fructose 1, 6 phosphate

(-) ATP and Alanine

127

Role of Phsophopyruvate kinase 1

products and reactants?

It converts fructose 6 phosphate -> fructose 1,6 phosphosphate

128

Where is energy put into glycoslisis? (2)

Where is energy extracted? (2)

w/ hexokinase/glucokinase
-glucose -> glucose 6 phosphate

w/ phosphofructosekinase 1
-> fructose 6 phosphate -> fructose 1, 6 phosphate

(gain)

phosphoglycerate kinase
->1,3 bisphosphoglycerate -> 3 phosphoglycerate

pyruvate kinase
-> Phosphoenolpyruvate (PEP) -> pyruvate

129

where does the following reactions take place?

Glycolysis
TCA cycle
oxidative phosphorylation

Glycolysis - cytolsol

TCA and oxidative phosphorylation - mitochondria

130

Which GLUT transporter is responsive to insulin

located where(2)

Glut 4

in skeletal muscle and adipose tissue

131

Which glut transporter is responsible for basal levels and independent go insulin

located where (2)

Glut 1

RBC and endothelium of BBB

132

Which Glut is regulatory and bidirectional (high capacity/ low affinity ) sensor

loacted (2)

Glut 2

Beta islet cells and hepatocytes

133

what 2 enzymes are responsible for regulation of glycolysis via Fructose 2, 6 bisphosphate?

Phosphofructokinase 2
-fructose 6 phosphate -> fructose 2,6 bisphosphate (encourages PFK1 action and responds to insulin)

Fructose bisphosphatase 2
-fructose 2,6 bisphosphate -> fructose 6 phosphate (encourages gluconeogenesis and responds to glucagon)

134

Fasting state leads to glucagon

What role dose that have on glucagon receptor and resulting G protein pathway

what G protein

Gs pathway - Glucagon receptor

High glucagon:insulin ratio
-> adenylate cyclase activation
-> increase in c AMP
-> protein kinase A activation
-> phosphorylates process dual enzyme

-> fructose bisphosphatase 2(active);
---->gluconeogenesis (raises blood glucose)
-> phosphofructokinase 2 (inactivated)

135

Fed state leads to insulin release

What role dose that have on glucagon receptor and resulting G protein pathway

what G protein

Gs Pathway - glucagon receptor

Low glucagon: insulin ratio
-> less adenylate cyclase activation
-> less cAMP made
-> less protein kinase activation
-> less phophorylation of the dual enzyme

-> fructose bis-phosphatease 2 is inactivated
-> phosphofructokinase 2 activated
---->glycolysis (encourage PFK 1)

136

Gibbs free energy equation

∆G = ∆H- T ∆S

137

why do we make glucose with gluconeogeneis?

due to the amount of energy gained from glucose molecules relative to ATP using gibbs free energy

PEP: -62 kJ
ATP: -31 kJ
AMP: -14 kJ

138

What are the 4 irreversible enzymes used in gluconeogenesis

pyruvate carboxylase
- pyruvate -> oxelacetate w/ biotin

PEP carboxylase
-oxeloacetate -> PEP

Fructose 1,6 bisphosphatase *
-Fructose 1,6 bisphosphate -> Fructose 6 phophate

Glucose 6 phosphatase
-glucose 6 phosphate -> glucose

139

Rate limiting step of gluconeogenesis

Modifiers
(1) increases
(2) decreases

fructose 1,6 bis phosphatase

ATP increases reaction

AMP and fructose 2, 6 decreases the reaction

140

What product up regulates pyruvate carboxylase action?

What co factor is needed?

acetyl Co A - too much going into the TCA cycle

Biotin

141

Rate limiting step of glycolysis

PFK 1 - Phosphofructokinase 1

142

Rate limiter of TCA cycle

isocitrate dehydrogenase

143

Rate limiter of glycogen synthesis

Glycogen synthase

144

Rate limiter of glcogenolysis

glycogen phosphorylase

145

Rate limiter of HMP Shunt

glucose 6 phosphate dehydrogenase

146

Rate limiter of de novo pyrimidine syntheis

carbamoyal phosphate synthetase II

147

Rate limiter of de novo purine synthesis

glutamine PrPP amidotransferase

148

Steps in making glycogen (4)

occurs where

occurs in both hepatocytes and skeletal- only skeletal muscle is lacking glucose 6 phosphatase so it does not release glycogen to the blood stream but utilizes it

hexokinase/glucokinase
-> glucose 6 phosphate
------------------
phospho-gluco-mutatse interconverts to
-> glucose 1 phosphate

UDP glucose phosphophorylase
-> UDP glucose

Glycogen syntase*
-> alpha 1, 4 bonds

branching enzyme
-> alpha 1, 6 bonds

149

Breakdown of glycogen (glycogenolysis) steps (2 enzymes)

Glycogen phosphorylase*
- breaks down alpha 1,4 bonds making "glucose 1 phosphate"

converted to glucose 6 P via phospo-gluco-mutase -> used in cell or if liver lose lose phosphate and exported

De-branching enzyme - 2 functions
- transferase: 4 alpha D glucotransferase (at 4 glucose residue)
- break down of last alpha 1-6 bond (alpha 1-6 glucosidase)

150

Regulation of glycogen synthesis

Role of insulin?

Role of glucagon?

Role of epinephrine?

glucagon acts at glucagon receptor
-> adenylyl cyclase
-> increase in cAMP
-> Protein kinase A
-> phosphorylates Glycogen phosphorylase kinase

Active glycogen phosphphorylase

Epinephrine does the same thing through beta 2 activation

Insulin activates a phosphoratase -> dephosphorylates glycogen phosphorylase

151

Which enzyme converts glucose 6 phosphate to glucose?

located where?

glucose 6 phosphatase -> liver enzyme mainly, not in skeleton

last step of gluconeogenesis and also in glycogenolysis

152

glycogen phosphorylase deficiency

McArdles Type V

153

Glucose 6 phosphatase deficiency

Von Gercks disease Type I

154

lactic acidosis, hyperlipidemi, hyper uricemia glycogen storage disease

Von Gercks disease (glucose 6 phosphatase)

155

alpha 1,6 glucosidase deficiency

Cori's disease (type III)

156

alpha 1, 4 glucosidase deficiency (Lysosomal)

Pompe's disease (type II)

157

cardiomegaly glycogen storage disease

pompe's disease infantile (type II) alpha 1-4 glucosidase lysosomal disease

158

diaphragm weakness -> respiratory failure glycogen storage disease

pomp's disease - adult (type II ) alpha 1-4 glucosidase lysosomal disease

159

increased glycogen in the liver severe fasting hypoglycemia

von gercks disease -glucose 6 phosphatase

160

hepatomegaly, hypoglycemia, hyperlipidemia, (normal kidneys, lactate and uric acid)

cori's disease (type III) alpha 1-6 glucosidase

161

painful muscle cramps, myoglobinuria w/ strenuous exercise

McArdles disease (type V) glycogen phosphorylase in skeletal muscle

162

severe hepatospleomegaly and enlarged kidneys glycogen storage disease

Von Gercks disease (type I) glucose 6 phosphatase

163

all the glycogen storage disease are acquired

auto recessive

164

4 uses of pyruvate

lacate (via LDH w/ NAPH)

oxaloacetate (via pyruvate carboxylase w/ ATP (gluconeo))

Alanine (via ALT and N added on )

Acytyl Co A (via pyruvate dehydrogense w/ B1, B2, B3, B5 and lipoic acid)

165

3 enzymes in the Krebs cycle worth knowing (irreversible)

citrate syntase
-Acytyl Co A -> Citrate

isocitrate dehydrogenase
-isocitrate -> alpha keto glutarate

alpha ketoglutarate dehydrogenase
-alpha ketoglutarate -> succinyl Co A

166

Regulation of pyruvate dehydrogenase requires what co-enzymes (5)

Same co enzymes w/ what other enzyme

TLC For Nobody

Thiamine pyrophosphate -(activated B1)
Lipoic Acid
Coenzyme A - Vit B5
FADH2 - B2
NADH - B3

Also used in alpha ketoglutarate dehydrogenase

167

Arsenic poisoning presentation?(3)

How does it affect the krebs cycle?

Garlic breath
vomitting
rice water stools

Blocks pyruvate dehydrogenase and alpha ketoglutarate dehydrogenase coenzyme: lipoic acid

168

Pyruvate dehydrogenase may be due to (3)

presenation?

X linked deficiency

Functional
-Arsenic poisoning(lipoic acid)
- Thiamine deficiency

presents as neurogenic defects

169

Rx for pyruvate dehydrogenase complex deficiency

increase ketogenic nutrients
(high fat content of increase lysine and leucine (ketogenic AA)

170

Electron transport complexes may be blocked by what?

Complex I (3)

Complex II

Complex III(1)

Complex IV(4)

ATPase (1)

Complex I
- amytoyl - a barbituate
- Rotenone - fish poison
- MPP

Complex II

Complex III
-antymycin A

Complex IV
- Cyanide - CN
-carbon monoxide - CO
-Azide - N3
-hydrogen sulfide (H2S)

ATPase
-oligomycin A

171

where does ATPase get the energy to make ATP

final electron acceptor in the electron chain?

from the H gradient built up in the intermenbrane space

1/2 O2 and 2 H-> H20 is the final e- acceptor

172

What substances can increase the inner permeability of the nner mitochondria membrane decreasing ATP synth but increasing heat(3)

uncoupling agents

- ASA
-Thermogenin (brown fat)
- 2,4 dinitrophenol (weight loss pill)

173

Cori cycle function?

anaerobic glycolysis

pyruvate in cell is made into lactate (via LDH) -> goes into circulation to the liver where Lactate -> pyruvate (via LDH); 6 ATP are then invested to make that glucose again to be shipped out

- lactate signal O2 starvation

174

Why is there high levels of alanine and glutamine in the serum?

main carriers of N from the tissue to the liver and eventual excretion in the urea cycle

175

What is generally involved i transamination?

transfer of AA to alpha ketoglutarate to form glutamate (add on one more NH3 to get glutamine)

the remaining deaminated AA is a ketoacid (such as pyruvate and used in energy metab,)

176

pyruvate and alanine are related how?

differ in 1 N group on the alanine

177

in addition to substrates what is required by all aminotransferases

B6
pyridoxal phosphate

178

what are the 2 most important amino transferases?

alanine aminotransferase
-alanine + alpha ketoglutarate glutamate and pyruvate

aspartate aminotransferase
- glutamate + oxaloacetate alpha ketoglutarate + aspartate

transferases named by donor N group.

179

Source of NADPH ?

Uses (4)

HMP shunt/ pentose phosphate pathway

1. Synthesis of cholesterol and FA
2. Generation of O2 free radicals in phagocytes
3. Protection of RBCs from oxidative damage
4. cytochrome p450

180

Rate limiting enzyme of the pentose phosphate pathway

2 major products

2 NADPH - used later in several processes
Ribulose 5 Pi (used in ribose backbone)

181

3 enzymes important in the generation of oxidative burst in phagosomes

NADPH oxidase
-> makes free oxygen radical

Superoxide dismutase
- free oxygen radical -> H2O2

Myeloperoxidase
- H2O2 -> HClO (hypochlorite /bleach)

182

Why does NADPH oxidase deficiency lead to increased risk of infection

Chronic granlumatous disease

Lose the cells ability to make H2O2 and then catalase positive cells degrade environmental H2O2

-> no substrate to make HCLO3 via myeloperoxidase

183

Role of NADPH and RBC health

H2O2 and other free radicals are reduced by glutathione while glutathione is oxidized to glutathione disulfide

Glutathione is regenerated w/ glutathione reductase which uses NADPH as an e- donator.

No NADPH, no protection from free radicals for RBC -> hemolysis (problem w/ G6PD deficiency)

184

G6PD is transmitted?

what is seen on a blood smear?(2)

X linked transmission -> lack of RBC protection from oxidative damage due to inability to reduce glutathione again

-> heinz bodies (oxidized hemoglobin in RBCs)
-> bite cells (splenic macrophages remove the heinz bodies)

185

Drugs and substances that may induce an oxidative crisis in someone w/ G6PD deficiency (9)

Antimalarias - chloroquine + primaquine
Nitrofurantoin
Dapsone
Sulfonamides
Isoniazid
Naphthalene
Fava beans
High dose
-Ibuprofen
-ASA

186

Defect in fructokinase presentation

Called?

essential fuctosuria

benign disease w, excess sugars in the blood and urine, some may spill into hexokinase for conversion

187

Enzyme deficient in fructose intolerance?

Rx?

Aldose B -> phosphate trapping on fructose (depletion of phosphates impair phosphorylation needed in gluconeogenesis and glycogenolysis

Rx: no fructose or sucrose (glucose and fructose)

188

Fructose intolerance presentation (5)

infant presenting 6-7 months (after starting new foods)

hypoglycemia
jaundice
cirrosis
vomiting
hepatomegaly

189

Enzyme deficiency that may lead to infantile cataracts, sugar in the urine, and not much else?

Galactokinase deficiency

Galactitol accumulates vis aldose reductase w/ excess galactose -> cataracts

190

Enzyme deficient in classic galactosemia

presentation

Galactose 1 phosphate uridyltransferase
- toxic accumulation

jaundice
FTT
hepatomegaly
infantile cataracts
mental retardation

191

Rx for classic galactosemia?

no galactose or lactose (galactose and glucose)

192

When are glycogen stores depleted?

10-18hrs after the last meal

193

when does gluconeogenisis begin post absorptive?

4-6 hrs

194

after 24 hrs since las meal what fuel is being produces and what is being used by what?

Glucose(via glycogenolysis- gylcogen is gone)
FA

Brain uses glucose
Muscles and other tissues use some glucose but predom FA

195

When does the body start to make ketone bodies

48 hrs after the last meal roughly
-glucose and FA is also made

Brain uses glucose predominantly but some ketones
Muscles use FA - but also some ketones

196

What cell only uses glucose no matter what state of starvation?

RBCs

197

What metabolic scenario favors synthesis of ketone bodies?

What are ketone bodies(2)

when production of acetyl CoA from FA beta oxidation overwhelms the TCA cycle oxidative capacity

acteto actetate -> Beta hydroxybutrate (w/NADH)

Acetoacetate also spontaneously breaks down into acetone to give fruity odor

198

What is the rate limiting enzyme to ketone body production

HMG Co Synthases

199

Urine test for ketone bodies detects

beta hydroxybutrate
NOT aceto acetate

200

How long until the brain preferentially uses ketone bodies?

what the muscle primary fuel sure at this time?

~5 days

Musclces use FA mainly but some Ketone

RBC still use glucose from gluconeogen

201

Overnight fast vs 3 day fast

% glucose
% ketone

overnight
- 90% from glucose - 2/3 glycogen, 1/3 gluconeogen

3 day
-60% ketone bodies - 1/2 aceto acetate, 1/3 beta hydroxybutrate
-40% glucose - from mostly glucose genesis

202

Why do you become hypoglycemic after having alcohol on an empty stomach

alcohol metabolism leads to generation of NADH

NADH presence takes away gluconeogenisis reactants from making more glucose and shunts them to making:

pyruvate -> lactate (acidosis)
oxaloacetate -> malate

leads to FA synthesis and accumulation in the liver

203

Acytyl CoA used in (4)

TCA cycle
FA synthesis
cholesterol synthesis
ketone synthesis

204

Kwashiokor cause and presentation

protein malnutrition ->

FLAME
-Fatty Liver
-Anemic
-Malnutrition
-Edema/Ascities

less protein for albumin and rapidly proliferating cells (RBCs and skin - lesions/ hair abnormalities)

205

Marasmus is due to

Presentation (3)

energy malnutrition

muscel wasting
lost of sub Q fat
variable edema

206

Refeeding syndrome is due to

Timeline to be concerned

rapid reabsorption of Mg, K and phosphate back into the cell w/ the nutrients now in the cell -> arrhythmia risk and neuro problems

Cells originally dumped electrolytes to maintain osmotic balance in the vasculature

starvation for more than 5 days

207

Chylomicrons are packaged where and leave?

Packaged in the enterocyte and leave via the lymph system into the blood around the L subclavian

208

Liver takes up chylomicron and LDL via

LRP a group of receptors that include LDL receptors

209

CETP

cholesteral ester transfer protein

transfers cholesterol picked up by HDL on to VLDL and LDL

210

Liver picks up the TG it needs via what enzyme

hepatic triglyceride lipase

211

cells in the periphery take up cholesterol rich LDL via

endocytosis, LDL receptor and clathrin coated endocytosis

212

LCAT

lecithin cholesterol acyl transferase

takes cholesterol from the periphery and places on HDL to dump on LDL or have it scavenged directly by the liver via SRB1

213

Cholesterol is made out of?

Rate limiting step?

made out of acetyl CoA

HMG CoA reductase is the rate limiting step

214

APO E

mediates reuptake of remnants

215

APO A I

Activates LCAT which leads to maturation of HDL as it takes on cholesterol from the periphery

216

APO C II

co factor w/ lipoprotein lipase that removes FFA from the lipid particles (VLDL, Chylomicrons, HDL)

217

APO B 48

mediates secretion of the chylomicrons from enterocytes into the lymph

218

APO B 100

mediates secretion of VLDL from the liver, binds to LDL receptor

219

LDL transfer of cholesterol vs HDL

LDL transports cholesterol to the periphery of cells while HDL transfers it to the lever

220

hyper chylomicronemia

defect (2)

Complications (3)

auto recessive defect in either:
- lipoprotein lipase
-apolipoprotein CII

(can't cut -> increase in chylomicrons and TG and cholesterol)

Pancreatitis,
hepatosplenomegaly,
eruptive/puritic xanthomas
(NO increased risk of atherosclerosis)

221

familial hyper cholesterolemia

defect

Complications(4)

Auto DOM defect in LDL receptors ->

-accelerated athersclorisis
-tendon xanthomas
-corneal arcus
-pancreatitis

222

hyper triglyceridemia

defect

complications

Auto DOM hepatic overproduction of VLDL,

pancreatitis

223

Abetalipoproteinemia presentation (5)

Defect?

auto recessive defect in microsomal triglyceride transfer protein (MTP) gene -> decrease in B 48 and B100; enterocytes overwhelemed w/ triglycerides b/c can't export

FTT
Streatorrea
acanthocytosis ( spiky RBCs)
Ataxia
night blindness (ADEK def)

224

young patient presents w/ ataxia, night blindness and acanthocytosis, and steartorrea

Abetatlipoproteinemia

can also have FTT,

histology shows lipid accumulation in the enterocytes due to inability to export w/lack of apo B48 and B100

225

atheromas

plaques in the blood vessels due to oxidized LDL -> inflammation

226

xanthomas

preferred location

lipid laden histiocytes (dendrites) in the skin

especially
-eyelids (xanthelasma)

227

tendinous xanthoma

preferred location?

lipid accumulation in the tendon

especially the achilles

228

corneal alcus

lipid deposition in the cornea (nonspecific

229

FA synthesis precursors?

Rate limiting step and location

acetyl CoA

acytyl CoA carboxylase in the cytoplasm

230

FA metabolism rate limiting step and location

occurs in the mitochondria after getting in with the carnitine shuttle

Carnitine acyltransferase 1 (carnitine palmitoyl transferase 1)

most commonly deficient is Acyl CoA dehydrogenase

Breaks down into: ketone bodes and TCA cycle

231

Carnitine deficiency is?

Presentation(3)

inability to transfer LCFA into the mitochondria for degradation

causes:
-weakness
-hypotonia
-hypoketoic hypoglycemia

232

hypoketoic hypoglycemia be suspicious of

defect in FA beta oxidation

most common enzyme acyl CoA dehydrogenase- 1st step in beta oxidation

233

Essential AA(9)

PVT TIM HaLL

Phenylalanine
Valine
Threonine

Tryptophan
Isoleucine
Methionine

Histidine
Leucine
Lysine

234

Acidic AA (2)

Aspartic Acid
Glutamic acid

(- charge at body pH)

235

Basic AA (3)

Histidine
Arginine
Lysine

Arg and His -> growth
His and Arg -> histones and nuclear localization

236

Catecholamine synthesis (6 steps)

phenylalanine -> tyrosine
-phenylalanine hydroxyase

tyrosine-> DOPA
-tyrosine hydroxylase

DOPA -> Dopamine
-DOPA decarboxylase

Dopamine -> NE
- vitamin C

NE -> Epi
- SAM

237

hormone that encourages Epi formation

cortisol

238

Thyroxine derived from

catecholamine pathway
- branch off tyrosine

239

melanin derived from

catecholamone pathway
- branch off dopamine

240

Tryptophan makes? (2)

Niacin (via B6) -> NAD/NADH

Serotonin (via BH4) -> melatonin (in pineal gland)

241

Niacin derived from what AA

Tryptophan (w/ B6)

242

Serotonin derived from what AA

Tryptophan

243

Histidine makes (1)

Histamine (via B6)

244

Histamine derived from what AA

Histitidine (w/B6)

245

Glycine makes (1)

Porphyrin(via B6) -> heme

246

heme and porphyrin precursor derived from what AA

glycine w/ B6

247

Arginine makes (3)

Creatine
Urea
Nitric oxide

248

Creatine is derived from what AA

Arginine

Urea, NO

249

Urea is derived from what AA

Arginine

Creatine, NO

250

NO is derived from what AA

Arginine

Creatine, Urea

251

Glutamate makes what (2)

GABA (via B6)

glutathione

252

GABA is derived from what AA

glutamate (w/ B6)

253

glutathione is derived from what AA

glutamate

254

Methionine makes what?

S Adenosyl methionine

255

S adenosyl methionine is derived from what AA

methionine

256

Rate limiting step in the Urea cycle?

where does it occur?

Carbamoyl phosphate syntetase I

in the liver (mart in the mitochondria part in the cytosol)

257

what AA can donate NH4 directly to the urea cycle

What AA is a found as a substrate in the urea cycle

Aspartate

Arginine
- step before arginase cleaves off urea w/ hydrolysis to create ornithine

258

Urea is made of what?

Where is the products sources?

Urea is made of 2 NH2 molecules attached to a C that has a double bond to O

1 NH2 is from aspartate
1 NH2 is from NH4 (dropped off by glutamine in the mitochondria)

259

Ornithine transcarbamolysis is important where?

in the urea cycle
transports NH4 containing Carbamoyal phosphate and combines it w/ ornithine to create citulline

May be deficient in a X linked recessive disorder interfering w/ ammonia excretion

260

Presentation of ornithine transcarbamoylase deficiency?

2 things in seen w/ labs

first few days of life w/ excess carbamoyal phosphate is converted to orotic acid (from pyrimidine synthesis pathway)

thus have orotic acid in blood and serum AND hyper ammonia -> Decreased BUN w/ no urea being made

Symptoms of hyper ammonia -> tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurred vision

261

Ammonia toxicity may be due to (2)

Presents as? (6)

Liver disease (hepatocyte damage -> impaired urea cycle)

Congenital abnormality in urea cycle (ornithine transcarbomolase deficiency - X linked)

Hepatoencephalopathy (TCA cycle inhibited due to alpha ketoglutarate depleated w/ excess NH4)

-tremor (asterixis/ liver flap)
-slurring of speech
-somnelance
- vomitting
-cerebral edema
- blurred vision

262

Rx for hyperammonia
(4)

decrease protein diet

Benzoate
phenylbutrate

biotin -> stimulate ornithine transcarbamoylase

263

Patient comes in w/ mental retardation, seizures, fair skin, and musty odor, a few days after birth

What are the 2 causes?

Dietary modifications?

Phenylalnine hydroxylase deficiency or BH4 (tetrahydrobiopterin deficiency)

Decreased diet in phenylaine (low aspartame and protein)

Increased tyrosine +/- BH4 if deficient

264

Presentation of PKU (6)

Auto recessive deficiency in phenylalanine hydroxylase

Fair skin (less melanin from catecholamine pathway)
musty odor
siezures
mental retardation
growth disorder
eczema

265

Patient's urine turns black when left out over extended periods and has arthralgias and maybe brown pigmented sclera

defect in?

alkaptonuria(ochronosis)

autosomal recessive defect in homogentisic acid oxidase deficiency (tyrosine degradation pathway -> homogentisic acid -X -> fumarate)

Homogentisic acid builds up in connective tissue, sclera, urine and cartilage -> arthralgia

Benign

266

alkaptonuria is a defect in what enzyme

homogentisic acid oxidase
-> build up up homogentisic acid which turns things brown/black (sclera, skin, urine) -> arthralgias

Tyrosine is not broken down as well

267

Homogentisic acid oxidase deficiency ->

Alkaptonuria (ochronosis) tyrosine breakdown issues

black urine left standing
brown/dark sclera/connective tissue
arthralgia w/ homogentisic acid buildup

268

phenylacetate, phenylpyruvate and phenyl acetate seen in the urine- be concerned w?

Presentation

PKU

Mousy odor
Siezures,
Mental retardaiton,
eczema
fair skin

269

Maternal PKU results in?

microcephaly
mental retardation
growth retardation
congenital heart defects

Phenylalanine build up is toxic to the babe

270

Albinism may be due to a few causes (3)

What is this called

Locus heterogeneity

Tyrosinase deficiency - auto recessive (can't make melanin from tyrosine)

Defective tyrosine transporters ( less tyrosine in melanocytes)

Failure of melanocyte migration

271

S adenosyl methionine acts as what

important in what 2 synthesis pathways

acts as methyl donator
- ATP and methionine make SAM -> homosystine post CH3 donation

Important in
-NE -> Epi
- synth of phosphocreatine

272

Regeneration of methionine in order to make SAM need ((3)

Folate
B12

deficiency leads to decrease anabolic pathways in CH3 donation

273

Homocystinuria is due to (3) auto recessive issues?

cystathione synthase deficiency
- converts homocysteine -> cystathione -> cysteine (AA)

decreased affinity of cystathione synthase for pyridoxal phosphate (B6)

homocysteine methyltransferase deficency
- (maybe low B12)
-Converts homocysteine to regen methionine which combines w/ATP to make SAM

274

Subluxation of the lens is a finding in 2 congenital issues

Marfans (upward deviation)

Homocystinuria (downward deviation)

275

Findings in homocystinuria (7)

homocysteine in the urine
tall
kyphosis
lens subluxation
atherosclerosis
mental retardation
osteoperosis

(due to cystathione synthase def, low B6 affinity, or homocysteine methyltransferase def)

276

Rx for each of the 3 causes of homosysenuria

cystathionine synthase deficiency
-low Methionine
-increased cysteine (essential now)
- increased B12 and B6

low affinity for pyridoxal phosphate by cystathionine synthase
-increase B6

homocystein methyltransferase def
- increase B12

277

Cystinuria is due to ?

Loss of what AA?(4)

defeciency in renal tubular AA transporter

Lose COLA
- Cysteine
-Ornithine
-Lysine
-Arginine

278

Cystinuria presents as?

Rx?

hexagonal crystals and stag horn calculi in a kid due to excess cysteine in the urine which precipitate out

Rx - alkalinize the urine w/ acetazolamide; good hydration

Lose COLA w/ renal tubular AA transporter def
- Cysteine
-Ornithine
-Leucine
- Arginine

279

defect in alpha ketoacid dehydrogenase presents as?(4)

maple syrup urine disease
- can't break down branched chain AA: Leucine, isoleucine and valine

CNS disorders
mental retardation
death
sweet smelling urine

280

maple syrup urine disease is due to?

what AA pathway is disrupted

alpha ketoacid dehydrogenase deficiency leads to inability to break down branched chain AA: leucine, isoleucine and valine

CNS defects, mental retardation , death, sweet smelling urine

281

Hartnup disease is due to?

presentation?(3)

deficiency in neutral AA transporter in the kidney -> loss of tryptophan in urine

-> can't make niacin -> pellagra

dementia, diarrhea, dermatitis

282

kid shows up to an ER w/ hematemisis and abdominal pain

A couple 6-72 hrs later the patient is in metabolic acidosis, what is going on?

Kid got into his mom's iron fortified vitamins

Cell death due per oxidation of membrane lipids

283

Acute and chronic presentation of iron poisoning

Acutely - hematoemesis -> hypo volumetric shock; Ab pain

Chronically - metabolic acidosis (6-72 hrs); GI scarring and obstruction 2-8 wks out

284

What is ferritin?

2 functions

it is an iron protein complex (ferric acid and apoferritin)

Used in cellular storage of iron in the hepatocyte
Acute phase reactant released into serum w/inflammation and infection -> less Fe for bacteria

285

What is transferrin?

iron deficiency has what effect on transferrin?

protein that binds to ferric molecules and transports them in plasma

1/2 life = 8 days

increased in iron def (body makes more decease it wants to shuffle Fe around in def)

286

Zinc is important in what? (3)

essential in what 2 enzymes?

formation of zinc fingers (TF motif) -> protein formation in times of synthesis (like healing)

essential for carbonic anhydrase and lactic dehydrogenase

immune system

287

Zinc deficiency manifests as(11)

delayed wound healing*
less adult hair
hypogonadism
less responsive immune system
anorexia/diarrhea
dysgenisa - taste
anosmia - smell
depressed mental function
Rash - around eyes, nose, mouth and anus (Acrodermatitis enteropathica)
Impaired night vision
Infertility

288

Patient presents w/ decreased night vision a new rash located around the eyes, mouth and anus and has cut that just does not seem to heal - Whats going on

maybe zinc deficiency

delayed wound healing*
less adult hair
hypogonadism
less responsive immune system
anorexia/diarrhea
dysgenisa - taste
anosmia - smell
depressed mental function
Rash - around eyes, nose, mouth and anus (Acrodermatitis enteropathica)
Impaired night vision
Infertility

289

basophilic stippling and microcytic anemia seen in?

lead poisoning

290

Signs of lead poisoning

Low IQ
hearing problems
impaired growth
impaired peripherla nerve function - wrist/foot drop
Lead lines (gingival- burtons lines; bone, teeth
anemia
cholic/ ab pain

291

Lead poisoning leads to inhibition of what 2 enzymes?

presents as

ferrochelatase and ALA dehydratase
- both involved in heme synthesis -> anemia

-> inhibits rRNA degradaion in RBC -> basophilic stippling

292

Sideroblastic anemia

see iron laden mitochondria w. defect in heme synthesis

microcytic

can be hereditary( X linked ALA synth defect)

Reversible - alcohol, lead, isoniazid

293

Rx for lead poisoning (3)

dimercaprol - severe

EDTA
Succimer

294

Kid has abdominal pain, decreased mental IQ and peripheral nerve path (wrist/foot drop), w/ burtons lines

Ask about what living situation

lead paint chips at home

burtons lines -> lead accum in gingiva

295

D2/ergocalciferol

ingested from plants

296

D3/cholecalciferol

consumed in milk or synthesized in skin

297

Vitamin D measured in serum?

25 hydroxycholecalciterol;
25 OH D3 -> storage form

Made by liver

298

active form of Vitamin D?

made by

calcetriol
1,25 (OH)2 D3

Made by the kidney

299

3 functions of Vitamin D

increased Ca, Phos and Mg absorption from the intestine

increased PTH dependent reabsorption of Ca in the distal tubule

increased bone mineralization

300

3 causes of Vit D deficency

1. lack of Vit D in diet
2. impaired hydroxylation of vit D to active form
3. reduced response to vitamin D

301

Vitamin D deficiency presentation in kids and adults?

Rickets - kids
-bone pain, bowing, path fractures, dental issues (increased PTH to raise serum levels leads to pathology)

*note: breast milk is deficient in Vit D - Supplement

Osteomalacia - adults
- hypocacemic tetany, muscle weakness and bone pain

302

Causes of Vit D excess (2) and presentation(3)

excess supplementation or sarcoidosis( increased activation of Vit D by epitheliod macrophages)

have hypercalcemia, loss of appetite and stupor

303

alpha tocopherol

Vitamin E

304

Vitamin Es function

antioxidant - prevents nonenzymatic oxidation of cell components by oxygen free radicals

- especially protective of RBCs (hemolytic anemia if absent)

305

patient presents w/ muscle weakness, hemolytic anemia and ataxia be thinking of?

Vitamen E deficiency/alpha tocopherol

306

Vit E deficency presents as(3)

hemolytic anemia - erythrocyte fragility

peripheral neuorpathy -> muscle weakness

spinocerebellar tract demylination -> Ataxia

307

vitamin K's function

made into active form where?

serves as a cofactor for gamma carboxylation of glutamic acid -> coagulation factors II, VII, IX, X, Protein C and S

synthesized by intestinal flora

308

Why are neonates given a shot of Vit K at birth

Breast milk does not contain Vit K

309

Deficiency of Vitamin K in neonates presents as

Why are they susceptible to deficiency?

neonatal hemorrhage w/ increased PT and aPTT
- normal bleeding times

Neonate intestines are sterile thus no Vit A synthesis

310

What can cause Vit K deficiency in adults (3)

warfarin toxicity
Antiepileptics - phenytoin
antibiotics - disrupts normal flora that makes Vit K

311

gamma carboxylation of glutamic acid importance?

uses Vit K -> coag factors

312

4 Functions of Vit C

1. Hydroxylation of proline and lysine in synthesis of collagen

2. Co factor in the synthesis of Dopamine -> NE
- dopamine hydroxylase uses

3. Facilitates absorption of Fe ( keeps Fe in reduced Fe2+ state) - drink Fe sup w/ orange juice

4. Antioxidant (used w/ Vit E)

313

ascorbic acid

Vit C

314

Scurvy presentation (7)

swollen gums
purpura eccymycoses/bruising
swollen joints
bleeding into joints -> hemarthrosis
anemia
poor wound healing
weak immune system

315

Vitamin A functions (4)

Antioxidant
maintains epithelial and mucous secreting membranes
immune system
Eye maintenance

316

Vitamin A is used in the Rx of (3)

Acne - tretinoin, isotretenoin
Measles
AML M3

317

Deficiency in vitamin A (4)

decreased night vision
xerophthalima - conjunctival dryness - ulceration
keratomalacia - wrinkling/ cloudy cornea
bitot spots - dry silver grey bulbar conjunctiva

318

Beta carotene

2 retinols bound together

319

keratomalcia and bitot spots may hint at
- maybe corneal ulceration

Vit A deficiency

Cornea wrinkling,

dry silver/grey bulbar conjunctiva

320

Female patient presents w/ a HA after too much Vitamin A- > wants the diagnosis

pseudotumor cerebri

321

Vitamin A toxicity

N/V
HA
intracranial pressure - pseudotumor cerebri
teratogen
aloplecia
+/- cirrosis
stupor
skin changes

322

What much be done before prescribing Vit A

pregnancy test

323

thiamine is essential for what 4 reactions?

pyruvate dehydrogenase
-pyruvate -> acetyl CoA

Alpha ketoglutarate dehydrogenase
-alpha ketoglutarate -> Succinyl CoA

Transketolase ( HMP shunt/ pentose phosphate)
- Ribulose 5Pi -> Ribose 5Pi

Branched chain AA dehydrogenase

324

Deficiency in thiamine presents as (4 main presentations)

impaired glucose breakdown and ATP depletion worsened after glucose infusion (heart and brain first)

Wernicke Encephalopathy
- enecphalopathy
-occulomotor dysfunction
- gait ataxia

Korsakoff
-memory loss
-confabulation

Dry beri beri
-polyneuritis w/ myelin degeneration

Wet beri beri
- cardiomyopathy and cardiac failure

325

Causes of thiamine deficiency - 3 clinical pictures

Malnutrition
- alcoholism

Malabsorbtion

Loss of water soluble vitamins
- dialysis

326

Wernicke encephalopathy presentation(3 main) and cause

acute thiamine deficiency -> medial dorsal nucleus of thalamus and mammalary body degradation

Encephalopathy
occulomotor dysfunction
gait/ataxia
stupor
coma
hypotenison
hypothermic

327

korsakof presentation (4) and cause

chronic thiamine deficiency -> medial dorsal nucleus of the thalamus and mammalary body degradation

memory loss - retrograde/anterograde
confabulation
apathy
personality changes

328

dry beri beri presentation(4) and cause

thiamine deficiency -> polyneuropathy w/ myelin degeneration (w/ lack of glucose breakdown)

toe/wrist/foot drop
muscle weakness
hyporeflexia
arreflexia

329

Wet beri beri presentation (4)and cause

thiamine deficiency -> lack of ATP w/ glucose breakdown halted

high output cardiac failure
edema
peripheral vasodialation
high output cardiac failure

330

Vitamin Cofactor in oxidation reduction reactions (2)

Riboflavin B2
Niacin B3

331

Riboflavin B2 function

deficiency presents as (3)

cofactor in oxidation/reduction reactions
-if it has dehydrogenase in its name
-> FMN and FAD

Cheilosis - angular fissures in the mouth
corneal vascularization
glossitis

332

Vitamin B3 used in ?

Deficiency presents as?

Niacin -> reduction/oxidation reactions
- in diet or made from tryptophan
-> NAD and NADP

Glossitis
Pellagara
-Dermitis
-Delerium
-Diarrhea

333

3 causes of Vitamin B3/ niacin deficiency

Hartnup disease - neutral AA transporter deficiency in kidney (less tryptophan)

Carcinoid syndrome (Tryptophan used up)

INH
(decrease in B6 and B3)

334

Vitamin given to raise HDL and lower LDL

symptom?

Niacin

Symptom of flushing

335

Vitamin B5/Pantothenate used in?

Deficiency leads to? (4)

component of CoA and FA synthesis

Dermatitis,
enteritis,
aloplecia,
adrenal insufficiency

336

Vitamin B6 used in?(4)

Deficiency leads to? 95)

pyridoxal phosphate is
-a cofactor in transamination (ALT/AST)
- Deamination
-Synthesis of AA
-->cystathione, heme, niacin, histamine,
-Synthesis of NT
--> 5HT, Epi, NE, GABA, Dopamine

Deficiency leads ->
-convulsion,
- hyper irritability,
-peripheral neuropathy
-glossitis/angular cheilosis
- sideroblastic anemia w/out heme

337

Patient presenting w/ convulsions, hyper irratability and glossitis may be deficient in what?

B6-> pyridoxal phosphate

less GABA leads to convulsions

338

Deficiency in B6 may be due to use of what?

INH

339

Vitamin B7/ Biotin is used in?

Deficiency presents as

carboxylation reactions- add on 1 C
- like pyruvate carboxylase and acetyl CoA carboxylase

deficiency is rare (maybe if eating egg whites (Avidin))
-> dermatitis, aloplecia, enteritis

340

Patient is a body builder and insists on diet containing pure egg whites, what is he at risk for

Biotin deficiency due to avidin in eggs binding and decreasing availability

341

Vitamin B9 is also known as?

Active form?

Folic acid

tetrahydrofolate (THF)

342

Importance of B9/folic acid?

deficiency leads to ?(7)

synthesis of and repair of the nitrogenous bases in DNA
- especially in rapidly dividing and growing cells
-> B9 is a coenzyme for 1 C transfer/methylation

deficiency leas to macrocytic megaloblastic anemia*
- NO neuro symptoms vs B12
growth failure
neural tube defects if pregnant*
glossitis
diarrhea
depression
confusion

343

megaloblastic anemia is found in? (2)

differ how (4)

Means?

folic acid and B12 deficiency

B12 has neuro symptoms, low serum levels, high homocysteine levels and increased MMA

megaloblastic means large cells - keep growing due to impaired DNA synthesis and can't divide
-> seen in the bone marrow and peripheral smear
-> anemia in Macrocytic RBC
->hypersegmented PMNs

344

Deficiency in Folic acid may be due to (4)

Drugs
-methotrexate
-phenytoin
-sulfonamides
-trimethoprim

345

Most common vitamin deficiency in the US?

Folic acid

-alcoholism and pregnancy

346

Vitamin that has cobalt associated w/ it?

B12 - cobalamin

347

Function of Cobalamin? (2 reactions)

Deficiency(2)

cofactor for :
homocysteine methytransferase
-->(homocysteine-> methionine and THF)
--> very important in DNA synthesis

methylmalmonyl CoA mutase
-> methylmalonyl CoA -> succinyl CoA

Deficiency leads to
-macrocytic megaloblastic anemia (hyper segmented PMNs)
- neurologic symptoms : paresthesis, subacute degeneration, dementia, memory loss, weakness)

348

Clinical picture for B12 deficiency(4)

Strict vegans/vegetarians

malabsrobtion
-celiac sprue
-enteritis
-diphyllobothrium datum

intrinsic factor deficiency
-pernicious anemia
-Gastric bypass

absence of terminal ileum
-Crohns

349

Pernicious anemia is due to ?

test for it how?

autoimmune attack of the parietal cell or intrinsic factor leads to a deficiency in B12

350

Schilling test used for detecting?

used for detecting radioactive B12 uptake
- if limited fluorescent B12 is in the urine then there is pernicious anemia

351

Where is B12 absorbed

in the terminal illium bound to intrinsic factor

352

peripheral neuropathy and glossitis? (2)

B12 and B6

353

pernicous anemia due to deficiency in?

B12

354

used in carboxylation reactions

Biotin B7

355

used by pyruvate dehydrogenase and alpha ketoglutarate

B1 thiamine

356

Vitamins critical for DNA synthesis

B9 and B12