Make Biochem MY BITCH Flashcards
(101 cards)
1
Q
What are the classical and vascular types of Ehlers Danlos syndrome
A
Classical is joint hypermobility adn seen with mutaiton in type V collagen
Vascular is vascular and organ rupture and see deficient Type III collagen
1
Q
What is going in on uniparental disomy?
Whats dif between Heterodisomy and Isodisomy
A
offspring gets 2 copies of chrom from 1 parent,none from other:
Herodisomy = meiosis I error
Isodisomy = meisosis II error
2
Q
What do we treat a pt with HGPRT deficiency with?
A
allopurinol (or febuxostat would be second line)
2
Q
Explain structure of cilia and the disease caused by Dyenin arm defect
A
9+2 arrangement of microtubles; axonemal Dynein-ATpase likns peripheral 9 doublets–> see bending of cilium by sliding
Kartageners: immotile cilia d/t dyenin arm defect: intertility (dsfnx sperm and dsfnx fallopian tube), bronchiectasis, recurrent sinusitus, situs inversus
2
Q
RLS in Urea cycle
A
Carbomyl Phostphate Synthetaes I
+ N-acetylglutamate
3
Q
What are the 3 steps for Elongation in protein synthesis
A
- Aminoacyl tRNA binds to Asite (excpet for initator methionine)
- rRNA catalyxes peptide bond formation, transfers growing polypeptide to AA in the A site
- Ribosome advances 3 NTs toward the 3’ end of mRNA, moves the tRNA to the p site
3
Q
RLS in Glycogenesis
A
Glycogen Synthase
+ Glucose-6-P, +insulin, +cortisol
-glucagon, -Epi
5
Q
Key steps in Protein synthesis during Initiation
A
Initiated by GTP hydrolysis and initiation factors put together the 40S ribosomal unit with the initiator tRNA–> then released when mRNA and ribosomal 60S assemble with them
= 80S
6
Q
RLS in Cholesterol Synthesis
A
HMG-CoA reductase
+insulin, +thyroxine
-Glucagon -Cholesterol
8
Q
Enz Deficiency responsible for SCID causing excess ATP and dATP imbalance in the nucleotide pool
A
Adenosine Deaminase: causes feedback inhibition on ribonucleotide reductase thus decrease DNA synthesis
9
Q
RLS in ketogenesis
A
HMG-CoA synthase
10
Q
Stain for the following
CT
Muscle
Epithelial cells
NeuroGlia
Neurons
A
Vimetin = CT
DesMin = Muscle
Cytokeratin= epithelial cell
GFAP = Neuroglia
Neurfilaments = Neurons
10
Q
What happens when we increase ethanol metabolism in regards to NADH/NAD+
A
Will increase NADH/NAD+ ratio in liver; leads to
Pyruvate –> malate (lactic acidosis)
OXA–> malate (prevents gluconeogenesis = fasting hypoglycemia)
Glyaldehyde-3-P –> Glylcerol-3-P (causes hepatosteatosis)
11
Q
Site of synthesis of secreatory proteins and N-linked oligosacharides addition to proteins
vs
unattached and synthesis of cytosolic and organellar proteins
vs
synthesize and secreate peptide NTs for secreation
A
Rough Endoplasmic reticulum
Free ribosomes
Nissl bodies
12
Q
Amino Acids necessary for PURINE synthesis
A
Purines make me GAG: glysine, Aspartate, Glutamine
12
Q
RLS in FA synthesis
A
Acetyl-CoA Carboxylase (ACC)
+insulin, +citrate
-Glucagon -Palmitoyl CoA
13
Q
EnZ takes Ethanol–> Acetaldehyde
EnZ takes Acetaldehyde–> Acetate
What drugs inhibit these enZ
A
Ethanol –> Acetaldehyde via Alcohol Dehydrogenase and inhibited by Fomepizole
Acetaldehyde–> Acetate via Acetaldehyde Dehydrogenase and inhibited by Disulfiram
14
Q
EnZ deficiency responsible for SCID
A
Adenosine Deaminase deficiency
15
Q
What makes rRNA, mRNA and tRNA and what does alpha-amanitin do?
A
RNA pol I = rRNA
RNA pol II = mRNA (inhibited by alpha amanitin from mushrooms=hepatotoxic)
RNA pol III= tRNA
*prokaryones only have 1 RNA polymerase that makes all these
16
Q
Prokaryotic only, degrades RNA primers and replaces them with DNA; can excise in 5’–3’ direction
A
DNA polymerase I
16
Q
Differences in following mutations;
Silent
Missense
Nonsense
Frameshift
A
silent: NT substitute for codes for same AA; often in 3rd position (tRNA wobble)
MIssense: NT substitution in changed AA (like in SS disease)
Nonsense: NT substitution that codes for early stop (UAG, UGA, UAA)
Frameshift: Deletion or insertion resulting in misreading of downstream NTs; get truncated shitty protein
17
Q
normally inhibit G1 to S progression, mutation here results in unrestrained cell division
A
p53 and Rb
18
Q
What is the start codon and what does it code for?
What are the stop codons?
A
Start = AUG; codes for methionine
Stops: UAA, UGA, UAG
19
Q
RSL in De novo pyrimidine synthesis
A
Carbamoyl Phosphate Synthetase II
20
Difference between Indirect and Direct ELISA
**Indirect**: uses test antigen to see if a specific antibody is present in the pts blood; a secondar antiB coupled to color generating enZ is added to detect first antibody
**Direct**: uses a test antibody to see if specific antiG present in pts blood; secondary antoB coupled to color generating enZ to detect it
21
RLS in Glycogenolysis
Glycogen Phosphorylase
+Epi, +Glucagon +AMP
-G-6-P, - insulin, -ATP
22
3 yo child comes in that shows signs of MR. Parents note that he has violent behaviors and often slaps his face. His labs show Hyperuricemia.
Dx?
Cause?
Tx?
Lesch-Nyan syndrome
deficiency in purine salvage from **absent HGPRT**
also (hyperuricemia, Gout, Pissed off, Retardation and dysTonia)
tx: Allopurinol or Febuxostat
24
Golgi is key distribution for proteins and lipids from ER--\> vesicles and plasma membrane
Modifies \_\_\_\_to serine and threonine and _____ to aspergine
Most importantly puts this on proteins that are destined for the lysosome
O-oligos to serine and threonine
N-oligoon aspartine
\*\*\*Mannose-6-Phosphate for lysosomal trafficking
25
Where RNA polymerase and other TFs bind to DNA upstream from gene locus; AT RICH sequence with TATA box and CAAT boxes
mutation here results in decreased level in gene transcription
Promoter region
26
Congentital microdeletion of short arum of Chrom 5 (46XX or XY) what is this and what do we see associated
Cri-du-chat
microcephaly, ID, high pitched mewing (cat like) cry, epicanthal folds and VSD
27
Mother comes in with her 3 yo daughter. She is worried she is falling behind her developmental milestones, both physically and mentally. The daughter has hypotonia and brittle, kinky hair. Dx and cause
Dx is Menkes diesase: CT disorder d/t impaired Cu absorption and transport: see decreased activity of lysyl oxidase (Cu is a cofactor) = brittle hair, MR, hypotonia
29
Membrane enclosed organelle key in catbolism of VLCFA, branched chain FA and AA, has oxidase + catalse to metabolize alcohol to make plasmogen
and
Barrel shapped protein that degrades damaged or ubiquitin tagged proteins and depends on Ca++
Peroxisome
Proteosome
30
Difference btwn these single strand DNA repair mech:
Nucelotide Excision repair
Base excision repair
Mismatch repair
Nucleotide excision repair: Endonucleases release oligoNT with the damaged base; DNA polymerase fills gap then ligase fills and reseals
Base excision repair: Base-specific glycolysase sees altered base and creates AP site; then one or more NT removed by AP-endonuclease that cleave the 5' end, lyase cleaves the 3' end and DNA pol fills the gap
Mismatch repair: newly made strand is recongnized as mismatched then get remoeved and gap is filled
31
What are the key nuclear localizing signals necessary to get in and out of nucleus?
Proline, Arginine, Lysine; need to be PALs to get in the nucleus club! and it requires ENERGY to get in
32
What are p-bodies (this is for you Megan!)
mRNA quality control occurs at cytoplasmic p-bodies that hve exonucleases, decapping enZ and microRNAs: mRNAS that can be sotred here for future translation
33
What metabolism takes place in the Cytoplasm
Glycolysis, FA synthesis, HMP shunt, Protein synthesis (RER), steroid synth (SER) and cholesterol synthesis
34
What are the key steps in collagen synthesis and where do they occur?
1. Synthesis in RER; make collagen alpha chains = precollagen (Gly-X-Y)
2. Hydroxylation (RER) of specific proline and lysine residues (need vit C)
3. Glycosylation (RER) of pro-alpha-chains residues and mae procollagen by H+ and S-S bonds--\> triple helix of 3 alpha chains (CC = Osteogensis Imperfecta)
4. Exocytosis of procollagen to ECM
5. Proteolytic processing OUTside fibroblast :Clevage of S-S bonds to get insoluble tropocollagen
6. Cross-linking (outside fibroblast) make Covalent Lysine-Hydroxylysine links to reinforce collagen fibrils
35
What metabolism occurs in the Mitochondria
Fatty acid oxidation, acetyl-CoA production, TCA cycle, oxidative phosphorylation
36
Rare disorders, often prsent with myopathy, lactic acidosis and CNS disease. Muscle biopsy shows ragged red fibers
Mitochondrial myopathies; has transmission only through the mother
37
RSL in
38
RLS in HMP shunt
Glucose-6-Phosphate Dehydrogenase (G6PD)
+NADP+
-NADPH
39
3 year child comes in with multiple fractures, blue sclera, poor hearing and poor dental hygeine.
Dx and cause of disease
Osteogenesis Imperfecta
Autosomal Dominant with decreased production of type I collagen
39
RLS in _Glycolysis_ and it's regultors
Glycolysis limited by: PFK-1
+ by AMP and F,2,6-BP
- by ATP and citrate
40
Normal fnx of Na/K pump?
What effect does Oubain have on the Na/K pump?
What about Glycosides?
Pump 3 Na out, bring 2 K+ in--\> the loss of Na+ creates a drive for the Na/Ca+ exchange (bring Na+ in and Ca++ out) to maintain low intracellular Ca++ in the heart for less cnx
Oubain inhibits via binding to K+ site
Glycosides (digoxin) will block Na/K pump thus get increase in intracellular Ca++ and increase force of cnx
42
What is the process of RNA processing starting with hnRNA
nuclear RNA makes hnRNA--\> mRNA then
Cappin at 5' prime end (7-methyguanine cap)
Polyadenylation of 3' end (signal is AAUAAA)
Splicing out introns
all this shit happens in nucleus
44
You want to clone yourself because, hey, you are AWESOME! How would you do that and what personality disorder do you suffer from?
Isolate eukaryotic mRNA of interst
Expose mRNA to reverse transcriptase to make cDNA
insert cDNA into bacterial plasmids with antibiotic resistance genes
transofrm recomb plasmid into bacteria and surviving bacterio go on antibiotic medium to make DNA
you have Narcissitic personality disorder you weirdo
45
RLS in Fatty Acid Oxidation
Acetyl-CoA carboxylase
+Insulin, +Citrate
-Glucagon, - palmitoylCo-A
46
RLS in TCA cycle
Isocitrate Dehydrogenase
+ by ADP
-by ATP or NADH
48
Responsible for accuracy of AA selection when you are building a protein
Aminoacyl tRNA synthetase; its the 'matchmaker' and there is 1 per AA, if correct match will make peptide bond
50
Difference btwn Southern, Northern, Western, S.Western blot
Southern: electrophoresis of DNA which is then visualized
Northern: RNA sample is electrophoresed; reflects level of gene expression
Western: protein is electrophoresed (confirmatory after HIV+ELISA)
S.Western: DNA-binding proteins are labeled
51
What drugs act on microtubules?
Microtubules Get Constructed Very Poorly
Mebendazole (helminthic)
Griseofulvin (fungal)
Colchisine (gout)
Vincristine/blastine (cancer)
Paclitaxel
52
Site of steroid synthesis adn detox of drugs and proteins, lack surface ribosomes adn ar in liver hepatocytes and parts of adrenal cortex and gonads
Smooth ER
53
What are the following structures in tRNA?
T-arm
D-arm
Acceptor stem:
T-arm; has the Thymine/suedouridine/cytosine sequenced needed for **t-RNA ribosome binding**
D-Arm: has dihyrouracil residues for **tRNA recognition** by correct aminoacyl-tRNA syntehase
Acceptor Stem: the **3' end with the CCA AA aceptor** site (think Can Carry Amino acids) also called the anti-codon
54
RLS in Gluconeogenesis
Fructose 1,6-Bis phosphatase
+ by ATP and Acetely-CoA
- by AMP, F,2,6, BP
55
How do we progress from G1 to Mitosis
G1--\> S: cycD binds CDK4 = cycD/CKD4 will phosphorlyate Rb thus Rb released from E2F
Unbound E2F transcribes shit needed for S phase and we get CycE binds to CDK2
CycE/CDK2 allows us to progress to S phase
G2--\> M: CycA to CDK2 results in mitotic prophase
cdc25 activatesCycB to CKD1 = CycB/CDK1
CycB/CDK1 break down env and lamins
56
Prokaryotic only: resonsible for elongation of leading strand by addine deoxynucleotides to the 3' end and elongates lagging strand til reaches primer of preceding fragement:
thus grow 5' to 3'
has exonuclease activity to 'proof read' each added NT in a 3'--5' direction
DNA polymerase III
57
What is difference and simularities in Prader Willis and Angelman
Both are dt imprinting on Chrom 15
Prader: maternal imprinting thus Paternal is deleted = hyperphagia, obesity, ID, hypogonadism, hypotonia
AngelMan= Paternal imprinting and gene from dad is silent whle Maternal is deleted; see inapp laughter, seizures, ataxia and severe ID
MAMA and POP for
Maternal gene, Angelman, Mood, Ataxia
POP= Prader, Obese, Papa
58
Elastin is the stretchy shit in lungs, large arteries, vocal cords, ligamenta flavum. What AA is it rich in?
Why is it so elastic?
How is it broken down?
What disease is it invovled in?
Rich in Proline and lysine
Has crosslinking extracellularly that gives it elastic properties
Broken down by elastase (this is inhibited by alhpa-1-antitrypsin)
Marfan see defect in fibrillin = sheath around elastin
Emphysema: from alpha-1AT deficiency
wrinkles from aging
59
RLS in De Novo Purine synthesis
PRPP
- AMP, -IMP, -GMP
60
Three Postranslational modifications to proteins
Trimming
Covalent alterations
Chaperone protein
Trimming: remove C or N termial polypeptides from zymogen to make mature poroteins
Covalent alterations: Phosphorylation/Glycosylation/Hydroxylation/ Methylation/ Acetylation and ubiquitination
Chaperone protein: intracell protein that facilitates or maintains protein folding (in yeast some are heat shock proteins like Hsp60 expressed at high temps to prevent denaturation)
61
6 mo old has coarse facial features, clouded corneas and decreased joint movement.
Labs show elevated levels of lysosomal enZ.
Dx and pathogenesis
I cell disease: lysosomal storage disorder
defect in Phosphotransferase results in NO 6-mannose-phosphate on proteins supposed to go to lysosome
62
What is nonhomologous end joining and what disease is it messed up in?
Brings 2 ends of DNA fragments together to repair ds breaks; messed up in ataxia telangiectasia
63
Nicotinamides (NAD+ from _____ NADP+) and flavin nucleotides (FAD+ from \_\_\_\_\_).
NAD+ is generally used in\_\_\_\_\_\_ processes to carry reducing equivalents away as NADH.
NADPH is used in\_\_\_\_\_\_ processes (steroid and fatty acid synthesis) as a supply of reducing equivalents.
vitamin B3,
vitamin B2
catabolic
anabolic
64
Phosphorylation of glucose to yield glucose-6-phosphate serves as the 1st step of glycolysis (also serves as the 1st step of glycogen synthesis in the liver). Reaction is catalyzed by either ____ or \_\_\_\_\_\_, depending on the tissue.
At low glucose concentrations,\_\_\_\_\_\_\_ sequesters glucose in the tissue.
At high glucose concentrations, excess glucose is stored in the liver.
hexokinase or glucokinase
hexokinase
65
Compare and contrast Hexokinase and Glucokinase
Location
Km and Vmax
INduced by insulin
Feedback inhibited by G-6-P
Hexokinase is in most tissues but NOT liver or B cells pancrease; Has a Low Km, Low Vmax. Not induced by insulin and IS **inhibited** by G-6-P
Glucokinase is in the Liver and B cells pancrease. Has HIGH Km and HIGH Vmax and is **induced** by insulin but not inhibited by G-6-P
66
What are the Irreversible steps in Glycolysis?
glucose--\> G-6-P by Hexokinase or Glucokinase
Fructose-6-P--\> Fructose 1,6 Bis PHosphate by Phosphofrucktokinase-1 (RLS)
PEP--\> Pyruvate via Pyruvate kinase
67
What steps in glycolysis requre ATP?
What steps Generate ATP?
Need ATP: Glucose--\> G-6-P by hexo or glucokinase and
Fructose-6-P --\> Fructose 1,6 Bisphosphate
Generate: 1,3 BPG--\> 3-PG and
PEP--\> pyruvate
68
Regulation by F2,6 BP
What 2 enZ are same bifuncitonal enZ and how are they regulated?
FBPase-2 (fructose bisphosphatase-2) and PFK-2 (phosphofructokinase-2) are the same bifunctional enzyme whose function is reversed by phosphorylation by protein kinase A.
69
Explain the regulation of PFK-2 and FBPase-2 in the fed and fasting state
**Fasting state**: HIGH glucagon--\> Increased cAMP--\> Increased protein kinase A--\> **Increased FBPase-2**, and DecreasedPFK-2: less glycolysis, more gluconeogenesis.
**Fed state**: HIGH insulin--\> Decreased cAMP--\> Decreased protein kinase A--\> Decreased FBPase-2, I**ncreased PFK-2,** more glycolysis, less gluconeogenesis.
70
What is the function of the Pyruvate Dehydrogenase Complex?
What 5 cofactors does it require?
What complex is it simular to?
Mitochondrial enzyme complex linking glycolysis and TCA cycle. Differentially regulated in fed/fasting states (active in fed state).
_Reaction_: pyruvate + NAD+ + CoAacetyl----\> CoA + CO2 + NADH.
1. Pyrophosphate (B1, thiamine; TPP)
2. FAD (B2, riboflavin)
3. NAD (B3, niacin)
4. CoA (B5, pantothenic acid)
5. Lipoic acid
Simular to alpha-keotoglurate
71
Your 2 yo son was play in your magical potion set and may have ingested something... he has rice-water stools, is vomitting and his breath smells like garlic. What enZ is inhibited?
Arsenic poisoning!
inhibits lipoic acid thus Pyruvate Dehydrogenase won't work!
(TLC For Nancy)
72
This causes a build up in pyruvate resulting in shunting to lactate and alanine. What is the EnZ defiency?
What do we do to treat these pts?
How will they present?
**Pyruvated DH complex deficienc**y: Causes a _buildup of pyruvate_ that gets shunted to lactate (via LDH) and alanine (via ALT). X-linked.
Findings: Neurologic defects, lactic acidosis, serum alanine starting in infancy.
Tx: INCREASE intake of ketogenic nutrients (e.g., high fat content or ***lysine and leucine).***
73
What Products do we get from the TCA cycle?
Where does the TCA cycle occur?
What is the RLS in this processes?
The TCA cycle produces: 3 NADH, 1 FADH2, 2 CO2, 1 GTP per acetyl-CoA = 10 ATP/ acetyl-CoA (2× everything per glucose).
occur in the **mitochondria.**
RLS**: Isocitrate Dehydrogenase**
74
75
What is the function of Citrate Synthase?
Isocitrate DH?
alpha-KG-Dehydrogenase?
All enZ in the TCA cycle
Oxa + Acetyl-CoA--\> (*citrate synthase*)--\> Citrate
Isocitrate--\> (Isocitrate Dehydrogenase)--\> alpha-KG
Alpha-KG--\> (alpha KG Dehydrogenase)--\> Succinly CoA
76
What is the location and purpose of the Electron transport chain
What role does NADH and FADH2 play?
**NADH** electrons from glycolysis _enter mitochondria_ via the malate-aspartate or glycerol-3- phosphate shuttle. **FADH2** (=1.5ATP) electrons are transferred to **complex II** (at a lower energy level than NADH = 2.5 ATP).
The passage of electrons results in the **_formation of a proton gradient_** that, coupled to **_oxidative phosphorylation_**, drives the **_production of ATP._**
77
What inhibits Complex I in the ETC
What inhibits Complex III?
What inhibits Complex IV?
What inhibits complex V?
Rotenone blocks Complex I (decrease gradient)
Antimycin A blocks Complex III (decrease gradient)
Cyanide and NO block Complex IV (decrease gradient)
Oligomycine block Complex V (blocks the ATP synthase)
78
What are common uncoupling agents of the ECT pathway and what do they do?
**2,4-Dinitrophenol** (used illicitly for weight loss), **aspirin** (fevers often occur after aspirin overdose), **thermogenin** in brown fat.
_Increase permeability of membrane,_ causing a proton gradient and O2 consumption. ATP synthesis stops, but electron transport continues. *Produces heat.*
79
What is the purpose of the HMP shunt (pentose phosphate pathway)
What products are generated?
Where in the cell does this occur?
Provides a **source of NADPH** from abundantly available glucose-6-P (NADPH is required for reductive reactions, e.g., glutathione reduction inside RBCs, fatty acid and cholesterol biosynthesis).
Additionally, this pathway **yields ribose** for _nucleotide synthesis_ and _glycolytic intermediates_.
2 distinct phases (oxidative and nonoxidative), both of which occur in the cytoplasm. No ATP is used or produced.
80
What is the difference between the oxidative and non-oxidative reaction in the HMP shunt?
Oxidative (irreversible) G-6-P--\> --\> (**G6PDH**)--\> CO2 + 2 NADPH + Ribulose-5-Pi
G6PDH is the RLS in the HMP shunt
Non-oxidative (reversible): Ribulose-5-P\<--- (Phophopentose isomerase/ transketolase)--\> Ribuse-5-P + G3P + F6P
81
What is the Respiratory Burst?
What role does it have in disease pathology?
Activation of phagocyte NADPH oxidase complex (in neutrophils and monocytes) to use O2 as a substrate. Key in immune response--\> get rapid release of ROS
NADPH key for generation and neutralization of ROS
**Myeloperoxoidase** is _blue-green heme containig pigment_ that gives sputum its color
CC: Chronic granulomatous disease: high risk for inection by catalase + species (S.aureus, Aspergillus) that acan neutralize their own H2O2 and leave phagocytes without ROS to fight infections
82
Glucose 6 Phosphate DH defiency has implications in several disease pathologies.
What is it's role in anemias and infections?
NADPH is necessary to **keep glutathione reduced,** which in _turn detoxifies_ free radicals and peroxides.
**LOW NADPH in RBCs** leads to _hemolytic anemia_ due to _poor RBC defense a_gainst oxidizing agents (e.g., f**ava beans,** sulfonamides, primaquine, antituberculosis drugs).
**Infection** can also _precipitate hemolysis (_free radicals generated via inflammatory response can diffuse into RBCs and cause oxidative damage).
83
You are doing rotations in the heme clinic and your attending has you looking at blood smears. He tells you one of them has a pt with G6PDH deficiency. What will you see on the slide? What is the inheritance?
**Heinz bodies**—denatured Hemoglobin precipitates within RBCs due to oxidative stress.
**Bite cells**—result from the phagocytic removal of Heinz bodies by splenic macrophages. Think, “Bite into some Heinz ketchup.”
X-linked recessive disorder; most common human enzyme deficiency; more prevalent among blacks.malarial resistance.
84
You are using your own cells to look for enZ deficiencies for FUN bc that's fun, right?!? You find you are lacking the enZ **fructokinase**. What symptoms do you have? Why has this happened to you?!?
Symptoms: f_ructose appears in blood and urine._ Pts are asymptomatic so stop freaking out
Disorders of fructose metabolism cause milder symptoms than analogous disorders of galactose metabolism because fructose doesn't get trapped in cellls
You got this because of genetics: Autosomal recessive
85
You stopped at a friends house to see their little 6 mo old child. Rascal is trying his first sip of juice today! yay, he loves it!
A few days later your friend calls saying her son has been vomitting and looks orange. What's going on?!?
**Hereditary deficiency of aldolase B**. Autosomal recessive. _Fructose-1-phosphate_ accumulates, causing a DECREASE in available phosphate, which *results in inhibition of glycogenolysis and gluconeogenesis.*
Symptoms present following consumption of fruit, juice, or honey.
Urine dipstick will be ⊝ (tests for glucose only); reducing sugar can be detected in the urine (nonspecific test for inborn errors of carbohydrate metabolism).
Symptoms: hypoglycemia, jaundice, cirrhosis, vomiting.
Treatment:Decrase intake of both fructose and sucrose **(glucose + fructose).**
86
Your neighbor has an 8 month old daughter. She is very cute but doesn't smile much. You are on your peds rotation and noticing she is behind on some milestones, she doesn't seem able to track objects. You mention your concern to your friends and they take her to be looked at and find out she has cataracts (shots are up to date and no infections)
Whats going on?
Hereditary **_deficiency of galactokinase._** _Galactitol accumulates_ if galactose is present in diet. Relatively _mild condition._ **Autosomal recessive.**
Symptoms: galactose appears in blood and urine, infantile cataracts.
May present as failure to track objects or to develop a social smile.
"galactoKINase and fructoKINase are KINDER deficiencies)
87
Your preceptor tells you to go follow Dr. Cowmilk for the remainder of the day as she is busy. You join her team as they are finishing up a case and hear them recommend to limit intake of Galactose and Lactose from the infants diet and explains to the mother that if they don't, the child may develope jaundice, hepatomegaly, infantile cataracts and may die.
What EnZ deficeincy does this child have?
Why does it cause these terrible symptoms?
Absence of **galactose-1-phosphate uridyltransferase.** Autosomal recessive. Damage is caused by _accumulation of toxic substances_ (including _galactitol_, which accumulates in the lens of the eye).
Symptoms: failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability. Can lead to E. coli sepsis in neonates.
Treatment: exclude galactose and lactose (galactose + glucose) from diet.
88
What enZ takes Glucose--\> Sorbital to trap it in the cell (will create osmotic gradient)?
What can sorbital be further converted into to avoid this osmotic gradient?
What cells lack the above enZ thus are at risk for osmotic damage?
Glucose--\> Sorbital via **aldose reductase.**
sorbitol --\> Rructose using **sorbitol dehydrogenase;**
tissues with an insufficient amount of this enzyme *are at risk for intracellular sorbitol accumulation, causing osmotic damage* (e.g., cataracts, retinopathy, and peripheral neuropathy seen with chronic hyperglycemia in diabetes).
\*Schwann cells, retina, and kidneys have _only aldose reductase._ Lens has primarily aldose reductase.
89
What is the difference between Primary and Secondary Lactose intolerance
I_nsufficient lactase enzyme_ --\>dietary lactose intolerance. Lactase functions on the brush border to digest lactose (in human and cow milk) into glucose and galactose.
**Primary**: age-dependent decline after childhood (absence of lactase-persistent allele), common in people of Asian, African, or Native American descent.
**Secondary**: loss of brush border due to gastroenteritis (e.g., rotavirus), autoimmune disease, etc. Congenital lactase deficiency: rare, due to defective gene.
Stool demonstratespH and breath showshydrogen content with lactose tolerance test. Intestinal biopsy reveals normal mucosa in patients with hereditary lactose intolerance.
90
How can you dx someone with lactase deficiency?
Stool demonstrates Decreased pH and breath shows Increased hydrogen content with lactose tolerance test. I
ntestinal biopsy reveals normal mucosa in patients with hereditary lactose intolerance.
91
What AA are Essential and what does that mean?
Glucogenic: methionine (Met), valine (Val), histidine (His).
Glucogenic/ketogenic: isoleucine (Ile), phenylalanine (Phe), threonine (Thr), tryptophan (Trp).
Ketogenic: leucine (Leu), lysine (Lys).
"Lucy & I Met Val For His Three Listed Trips" or PVT TIM HaLL
92
What are the Basic and Acidic Amino Acids?
Basic: Arginine (Arg), lysine (Lys), histidine (His). Arg is most basic.
His has no charge at body pH.
Acidic: Aspartic acid (Asp) and glutamic acid (Glu). Negatively charged at body pH.
93
What is the purpose of the Urea cycle?
**Amino acid catabolism** results in the f_ormation of common metabolites_ (e.g., pyruvate, acetyl- CoA), which serve as metabolic fuels. _Excess nitrogen (NH3)_ generated by this process is _converted to urea and excreted_ by the kidneys.
94
Patients with Hyperammonium obviously have too much NH4+, but why is this such a big deal?
What symptoms will we see?
How can we treat pts with Hyperammonium?
Can be acquired (e.g., liver disease) or hereditary (e.g., urea cycle enzyme deficiencies).
Results in **excess NH4+**, which _depletes α-ketoglutarate_, leading to _inhibition of TCA cycle._
Symptoms: tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision
**Treatment**: limit protein in diet. **Lactulose** to acidify the GI tract and _trap NH4+_
for excretion. **Rifaximin** to DECREASE colonic ammoniagenic bacteria. **Benzoate** or **phenylbutyrate** (both of which bind amino acid and lead to excretion) may be given to DECREASE ammonia levels
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Newborn with poorly regulated respiration and body temperature, poor feeding, developmental delay, intellectual disability and High NH4+ levels in urine. What could be going on?
N-Acetlyglutamate defiency (or Carbomoyl phosphate synthetase I defiency)
Required cofactor for **carbamoyl phosphate synthetase I.**
Absence of N-acetylglutamate --\>hyperammonemia.
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Newborn baby is showing signs of Hyperammonium
You draw labs and it shows the following:
High Orotic acid in blood and urine
LOW BUN
DX?
**Ornithine tranxcarbamulase deficiency**
Most common urea cycle disorder_. X-linked recessive_
Interferes with the body’s *ability to eliminate ammonia.* Often evident in the first few days of life, but may present later. _Excess carbamoyl phosphate is converted to orotic acid_ (part of the pyrimidine synthesis pathway).
Findings: HIGH orotic acid in blood and urine, LOW BUN, symptoms of hyperammonemia. No megaloblastic anemia (vs. orotic aciduria).
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\_\_\_\_\_ may be located anywhere upstrea, downstream or within the transcribed gene.
\_\_\_\_\_\_ are located 25 bp upstream from associated genes
\_\_\_\_\_ are lcated 70 bp upstream from gene
Enhancers
TATA box
CAAT
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Major AA responsible for transfering Nitrogen to the liver for disposal
During catabolism fo proteins, AA groups are transferred to Alhpa-ketoglutarate to form glutamate; which is then processed in liver to make urea and is primary disposal form of nitrogen in humans.
Alanine
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Has 5' to 3' exonuclease actvity in addition to 5' to 3' polymerase and 3' to 5' exonuclease activity. The 5' to 3' exonuclease activity is used to remove RNA primer (which initiates DNA polymerization) and to remove damaged DNA.
DNA polymerase 1
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What is the role of snRNPs
Key in splicing! They are make by RNA pol II and help remove introns from teh RNA transcript. Need them to make mRNA
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What is the role of snRNPs
Key in splicing! They are make by RNA pol II and help remove introns from teh RNA transcript. Need them to make mRNA
