Biochem Phys Flashcards
1
Q
link between glycolysis and TCA cycle
A
Pyruvate Dehydrogenase
2
Q
nuclear localization signal?
3
A
marks a protein to enter the nucleus made of proline, lysine and arginine
3
Q
vimentin
Associate w?
A
intermediate filament in connective tissue
sarcomas
4
Q
desmin
associate w?
A
intermediate filament in muscle
associate w/ myosarcoma- leiomyosarcomas and rhadbomyosarcoma
5
Q
cytokeratin
associate w/
A
intermediate filament in epithelial cells
Associate w/ carcinoma
6
Q
GFAP
associate w/
A
intermediate filament in glial cells
Associate w/ astrocytoma and gliobastoma
7
Q
Neurofilaments
associate w/
A
intermediate filament in neurons
Associate w/ neuroblastoma and primitive neuroectoderma tumors
8
Q
Nuclear lamina ABC
associate w?
A
intermediate filaments making up the nuclear envelope
associate w/ mutations -> progeria (old age)
and muscular dstrophy
9
Q
Microfilaments function?
A
actin and myosin
- cellular motility
10
Q
Microtubule function
A
movement - cilia, flagella and mitotic spindle
11
Q
Intermediate filaments function
A
cellular skeleton - differs w/ each ell used to ID cancer etiology
12
Q
retrograde movement on microtubule
A
dynein
13
Q
anterograde movement on microtubule
A
kinesin
14
Q
Tyrosine Kinase receptor Examples and how composition (4)
A
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
Q
Improper clathrin and adapt in leads to
A
inability for receptor binding lwading to endocytosis-> can’t bring in
- recycled
16
Q
Phosphatydalinositol?
enzyme that acts on it?
A
cell membrane phospholipid that leads to AA
Phosolipase A2
17
Q
Drug blocking leukotrien production and MOZ
A
Zilueton
blocks lipoxygenase
18
Q
Of the leukotriene receptor antagonist, which is best to give to a kid
A
Montelukast
Not as much Zafirlukast
19
Q
Action of Leukotrienes (2)
A
Chemotaxis of PMN- LTB4
Increases bronchial tone - LTC4 and LTD4
20
Q
Action of prostacyclin (4)
A
PGI2 Decreases uterine contraction Decreases platelet aggregation Decreases brachial tone Decreases vascular tone
21
Q
Action of prostaglandins (4)
A
PGE2 and PGF2A Increases uterine contraction Increases gastric mucosa production Decreases vascular tone (KEEEEPS open) Decreases bronchial tone
22
Q
Action of thromboxane (3)
A
TxA2 Increases platelet aggregation increases bronchial tone Increases vascular tone (opposite of PGI2)
23
Q
APAP - acetaminophen’s action vs other COX inhibitors
A
Inactivated peripherally thus no anti inflammatory or anti platelet action
24
Q
BCL-2
A
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
