What are the classical and vascular types of Ehlers Danlos syndrome
Classical is joint hypermobility adn seen with mutaiton in type V collagen
Vascular is vascular and organ rupture and see deficient Type III collagen
What is going in on uniparental disomy?
Whats dif between Heterodisomy and Isodisomy
offspring gets 2 copies of chrom from 1 parent,none from other:
Herodisomy = meiosis I error
Isodisomy = meisosis II error
What do we treat a pt with HGPRT deficiency with?
allopurinol (or febuxostat would be second line)
Explain structure of cilia and the disease caused by Dyenin arm defect
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
RLS in Urea cycle
Carbomyl Phostphate Synthetaes I
What are the 3 steps for Elongation in protein synthesis
1. Aminoacyl tRNA binds to Asite (excpet for initator methionine)
2. rRNA catalyxes peptide bond formation, transfers growing polypeptide to AA in the A site
3. Ribosome advances 3 NTs toward the 3' end of mRNA, moves the tRNA to the p site
RLS in Glycogenesis
+ Glucose-6-P, +insulin, +cortisol
Key steps in Protein synthesis during Initiation
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
RLS in Cholesterol Synthesis
Enz Deficiency responsible for SCID causing excess ATP and dATP imbalance in the nucleotide pool
Adenosine Deaminase: causes feedback inhibition on ribonucleotide reductase thus decrease DNA synthesis
RLS in ketogenesis
Stain for the following
Vimetin = CT
DesMin = Muscle
Cytokeratin= epithelial cell
GFAP = Neuroglia
Neurfilaments = Neurons
What happens when we increase ethanol metabolism in regards to NADH/NAD+
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)
Site of synthesis of secreatory proteins and N-linked oligosacharides addition to proteins
unattached and synthesis of cytosolic and organellar proteins
synthesize and secreate peptide NTs for secreation
Rough Endoplasmic reticulum
Amino Acids necessary for PURINE synthesis
Purines make me GAG: glysine, Aspartate, Glutamine
RLS in FA synthesis
Acetyl-CoA Carboxylase (ACC)
-Glucagon -Palmitoyl CoA
EnZ takes Ethanol--> Acetaldehyde
EnZ takes Acetaldehyde--> Acetate
What drugs inhibit these enZ
Ethanol --> Acetaldehyde via Alcohol Dehydrogenase and inhibited by Fomepizole
Acetaldehyde--> Acetate via Acetaldehyde Dehydrogenase and inhibited by Disulfiram
EnZ deficiency responsible for SCID
Adenosine Deaminase deficiency
What makes rRNA, mRNA and tRNA and what does alpha-amanitin do?
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
Prokaryotic only, degrades RNA primers and replaces them with DNA; can excise in 5'--3' direction
DNA polymerase I
Differences in following mutations;
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
normally inhibit G1 to S progression, mutation here results in unrestrained cell division
p53 and Rb
What is the start codon and what does it code for?
What are the stop codons?
Start = AUG; codes for methionine
Stops: UAA, UGA, UAG
RSL in De novo pyrimidine synthesis
Carbamoyl Phosphate Synthetase II
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
RLS in Glycogenolysis
+Epi, +Glucagon +AMP
-G-6-P, - insulin, -ATP
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.
deficiency in purine salvage from absent HGPRT
also (hyperuricemia, Gout, Pissed off, Retardation and dysTonia)
tx: Allopurinol or Febuxostat
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
***Mannose-6-Phosphate for lysosomal trafficking
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
Congentital microdeletion of short arum of Chrom 5 (46XX or XY) what is this and what do we see associated
microcephaly, ID, high pitched mewing (cat like) cry, epicanthal folds and VSD
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
Membrane enclosed organelle key in catbolism of VLCFA, branched chain FA and AA, has oxidase + catalse to metabolize alcohol to make plasmogen
Barrel shapped protein that degrades damaged or ubiquitin tagged proteins and depends on Ca++
Difference btwn these single strand DNA repair mech:
Nucelotide Excision repair
Base excision 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
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
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
What metabolism takes place in the Cytoplasm
Glycolysis, FA synthesis, HMP shunt, Protein synthesis (RER), steroid synth (SER) and cholesterol synthesis
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
What metabolism occurs in the Mitochondria
Fatty acid oxidation, acetyl-CoA production, TCA cycle, oxidative phosphorylation
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
RLS in HMP shunt
Glucose-6-Phosphate Dehydrogenase (G6PD)
3 year child comes in with multiple fractures, blue sclera, poor hearing and poor dental hygeine.
Dx and cause of disease
Autosomal Dominant with decreased production of type I collagen
RLS in Glycolysis and it's regultors
Glycolysis limited by: PFK-1
+ by AMP and F,2,6-BP
- by ATP and citrate
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
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
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
RLS in Fatty Acid Oxidation
-Glucagon, - palmitoylCo-A
RLS in TCA cycle
+ by ADP
-by ATP or NADH
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
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
What drugs act on microtubules?
Microtubules Get Constructed Very Poorly
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
What are the following structures in tRNA?
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
RLS in Gluconeogenesis
Fructose 1,6-Bis phosphatase
+ by ATP and Acetely-CoA
- by AMP, F,2,6, BP
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
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
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
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
RLS in De Novo Purine synthesis
- AMP, -IMP, -GMP
Three Postranslational modifications to proteins
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)
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
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
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.
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
Compare and contrast Hexokinase and Glucokinase
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
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
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
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.
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, Increased PFK-2, more glycolysis, less gluconeogenesis.
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
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?
inhibits lipoic acid thus Pyruvate Dehydrogenase won't work!
(TLC For Nancy)
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 deficiency: 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).
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
What is the function of Citrate Synthase?
All enZ in the TCA cycle
Oxa + Acetyl-CoA--> (citrate synthase)--> Citrate
Isocitrate--> (Isocitrate Dehydrogenase)--> alpha-KG
Alpha-KG--> (alpha KG Dehydrogenase)--> Succinly CoA
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.
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)
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.
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.
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 Ribuse-5-P + G3P + F6P
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
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 against oxidizing agents (e.g., fava beans, sulfonamides, primaquine, antituberculosis drugs).
Infection can also precipitate hemolysis (free radicals generated via inflammatory response can diffuse into RBCs and cause oxidative damage).
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.
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: fructose 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
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).
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)
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.
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.
What is the difference between Primary and Secondary Lactose intolerance
Insufficient 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.
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.
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
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.
What is the purpose of the Urea cycle?
Amino acid catabolism results in the formation 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.
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
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.
Newborn baby is showing signs of Hyperammonium
You draw labs and it shows the following:
High Orotic acid in blood and urine
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).
_____ 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
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.
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
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
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