Seneca
You will find short youtube videos that will help you picture concepts in your mind. Next to the videos, I write high-yield information and corresponding UWorld QIDs.
-MTX prevents formation of tetrahydrofolate by stopping DHF reductase. Dihydrofolate polyglutamate will therefore accumulate.
--N5formyl tetrahydrofolate (folinic acid, leucovorin) supplementation to overcome the chemotherapeutic effect of MTX.
-5FU is converted to a molecule that gets in the way of thymydilate synthetase. FA page 34
UW 1857
-Without Adenosine deaminase, which removes the amino group from adenosine/deoxyadenosine, there isn't formation of the excretable nontoxic products. Instead, we get the toxic deoxyadenosine triphosphate -> activation of caspase and inhibition of ribonucleotide reductase, so dysfunction of immune cells.
-ADA inhibitors can be used to treat hairy cell leukemia.
-The most common genetic form of typical SCID is mutation in the X-linked gene IL2RG, encoding the interleukin 2 receptor gamma chain, also called the common cytokine receptor gamma chain (gamma-c).
UWQID : 15293
The daughter strand is synthesized in opposite direction of the growing replication fork . Once the primer is laid down, you’ll get chunk by chunk of short dna fragments.
UWQID 1418
Endonuclease is able to detect the pyrimidine dimers caused by UV radiation. It then nicks it on to allow for repair.
In xeroderma pigmentosum, there is a deficiency in UV-specific endonuclease, leading to increased risk for skin cancer.
UWQID 883,1477, 1476,
If you lose the ribosomes attached to the rough ER, like with ischemia, then you lose ability to synthesis cell membrane proteins.
First aid page 45
UWQID 757
If ubiquitination is affected, less protein will be degraded by the proteosome. There will be more proteins; that's regardless of mRNA level.
UWQID 107732
Glycine is the amino acid that is the most plentiful in Collagen. Every third position is glycine. UWQID 1248
Sketchy First aid page 48
- Ehlers danlos abnormal collagen formation.
-Hypermobile joints, hyperelastic skin, easy bruing, wounding, hemarthosis.
- Collagen is not formed well because N terminal propeptide is not removed/cleaved due to deficiency of procollagen peptidase, in the extracellular space. First aid page 49 UWQID 1245
FIrst aid page 52
PCR
Mitochondrial Heteroplasmy= cells will contain both normal and mutant mitochondrial.
First Aid page 55
UWQID 596
-Edwards syndrome (trisomy 18) has the following chromosomal abnormality: 47, xx+18. An extra copy of chromosome 18 is present due to meiotic nondisjunction.
-This is an error prior to oocyte divisin, therefore associated with increased maternal age.
-Look out for overlapping fingers (absent in trisomy 13).
First aid page 61 . FA mnemonic: PRINCE Edward- Prominent Occiput, Rocker bottom feet,Intellectual disability,Nondisjunction, Clinched fist with overlapping fingers, Ears low set. Election age 18. Ed every prenatal screening marker decreased.
UWQID 1823
-
If a patient comes in for CF counseling and has an affected father (F508 mutation) and unaffected unknown carrier status of her mom, and CF maternal aunt affected (F508), and Maternal grandpa and grandma not affected. Mother will have 2/3 chance of being a carrier, even if carrier still 1/2 chance of passing it. So have to multiply 2/3*1/2 = 1/3
-Sickle cell two carrier parents - child has 50% chance inheriting Aa, 25% aa. If question asking what are chances of child inheriting one or more mutated alleles , then you add. 75% FA page 57
Bitot's spots, dry eyes (xerophtalmia), and night blindness (nyctalopia) indicate vitamin A deficiency. Bitot spots represent conjunctival metaplasia, which happened because no vitamin A to suppress that metaplasia.
Remember the importance of vitamin A in the differentiation process needed to form the conjunctiva covering of the eye. WIthout vitamin A, metaplasia occurs. As can be seen in the video.
UWQID 806
First aid page 64
Eye motor abnormalities in Wernicke encephalopathy,
First aid page 64 First aid mnemonic CorONA beer-> Confusion, Ophtalmopathy/Nystagmus, Ataxia
UWQID 63
A heavy alcohol drinker with pins and needles in legs, painful lip and mouth lesions, with glossitis and angular stomatitis on p/e, hepatomegaly is found to have low urinary riboflavin excretion. - riboflavin deficiency means the B2containing coenzymes won't function. FAD is a coenzyme for succinate dehydrogenase.
First aid page 65
UWQID 1807
The hydroxylation of proline and lysine need vitamin C as a cofactor. It happens in the rER. Without it, collagen doesn't have its maximal tensile strength. First aid page 67
UW QID 311
-Alcohol inhibits gluconeogenesis. So when patients, ,like alcoholics, don't eat for days , they will be hypoglycemic when glycogen stores are depleted.
-Ethanol metabolism leads to NAD becoming NADH. Increase of NADH/NAD ratio. Lactate can't be converted to pyruvate, malate can't be converted to oxaloacetate
First aid page 70
UWQID 1019, 370
Lysine and leucine are ketogenic aa and are needed to for patients with PDH deficiency
UW QID 998
If you have LDH deficiency, then you won't be able to regenerate NAD. When you exercise, NAD wont be regenerated by ETC. So that leads to intracellular depletion, that's where LDH should be coming in.
- NAD is required to convert glyceraldehyde 3 phosphate to 1,3 bisphosphoglycerate in glycolysis.
UWQID
First aid page 75
-Niacin is a precursor for NAD, which is required for the enzyme isocitrate dehydrogenase in the TCA cycle.
-Lack of NAD affects isocitrate dehydrogenase (among other enzymes elsewhere)
UWQID
First aid page 75
-Phoshoenolpyruvate is formed from oxaloacetate in a reaction that requires GTP. In the TCA cycle, GTP is made when succinyl coa becomes succinate by the enzyme succinyl coa synthetase.
QID: 1022
Acetyl coa (broken down from fatty acids in fasting) will stimulate gluconeogeneiss by stimulating pyruvate carboxylase.
First aid mnemonic : Pathway Produes Fresh Glucose -Pyruvate carboxylase, phosphoenol pyruvate carboxykinase, Fructose 1,6 bisphosphatase 1, glucose-6-phosphatase
-Glycolysis, fatty acid synthesis , and pentose phosphate pathway enzymes reside in cytosol. Transketolase is an enzyme of PPP that uses thiamine.
-G6PD takes glucose 6 phosphate and converts it to 6 phosphogluconate (rate limiting step), and then it becomes ribulose 5 phosphate. The NADPH generate is necessary for fatty acid synthesis.
UWQID 894
If pureed food is added to a 6 month's old diet and the patient now has severe hypoglycemia, a diagnosis test likely to confirm aldolase B deficiency.
-Avoid fructose and sucrose
-Acumulation of F1P depletes intracellular phosphate and inhibits activation of hepatic phosphorylase, and gluconeogeneis.
UWQID 1069
BB First aid page 78
-When fructokinase doesn't work in Fructokinase deficiency, Fructose doesn't get converted to fructose 1 P.
- That fructose can be convered by hexokinase into fructose 6 phosphate as a compensatory solution. That Fructose 6 phosphate goes into glycolysis, bypassing the first step of hexokinase that was converting glucose into glucose 6 phosphate.
-Copper reduction test can be positive.
FA Mnemonic: Fructokinase deficiency is kinder.
QID: 1070
-Patients with galactosemia due to galactokinase deficiency can present with cataracts. The back up of galactose will be converted to galactitol by aldose reductase.
-Caract can be the only sign in galactokinase deficiency. -Classic galactosemia enz def : Galactose 1 phosphate uridyltransferase
UWQID 1071
First aid page 78
-One way to mess up the urea cycle is failing to get ornithine from the cytosol and into the mitochondria.
-Another way, more commonly, is to have a deficiency in Ornithine transcarbomylase. In that case ornithine can't combine with carbamoyl phosphate to form cittrulline. Excess carbamoyl phosphate will then stimulate pyrimidine synthesis.
UWQID 1370, 1372
Arginase produces urea and ornithine from arginine.
UWQID 1480
--Alanine's amino group is transferred to alpha ketoglutarate, as it is transaminated to become pyruvate. Alanine is released by catabolism in skeletal muscle to carry out nitrogen. As part of the alanine-glucose cycle, it then goes to liver either for source of nitrogen waste or source for carbons for gluconeogenesis.
-The amino acid Glutamate reacts with oxaloacetate, a keto acid, to form aspartate and a ketoglutarate.
UWQID 1369
- Problem is a conversion of phenylalanine to tyrosine. The diet should not have phenylalanine. They also need supplementation of tyrosine.
-Phenylanaline hydroxylase also won't be able to convert phenylalanine to tyrosine if dyhydropterine reductase doesn't give it BH4.
-What other enzymes need BH4 as a cofactor?
Tyrosine hydroxylase - to convert tyrosine into Ldopa. Tryptophan hydroxylase to convert tryptophan into 5 hydroxytryptophan, which then can be converted to serotonin. Sketchy
https://pubmed.ncbi.nlm.nih.gov/34017006/ First aid page 82
UWQID 1500
--When cystathionine synthase is deficient (most common cause of homocystinuria), homocysteine can't be converted to cystathione and subsequently no cysteine.
-Methionine will be high because some homocystein converted the other way. Methioning is a risk factor for thrombosis.
First aid page 83
UWQID 1504
-HIgh plasma methionine is Independent risk factor for thrombosis. Look for STEMI and increased troponin if chest pain.
-One possible cause is genetic mutation in MTHFR gene. MTHFR is part of folate cycle, gives methionine synthase the folate it needs to convert homocysteine to methionine, as part of methionine cycle.
UWQID 788
No glycogen receptors in muscles. Glycogenolysis in muscle happens with muscular contraction, a process where calcium is released and activates phosphorylase kinase, stimulating glycogen phosphorylase.https://pubmed.ncbi.nlm.nih.gov/1899238/
First aid page 84
UWQID 1028
-Muscle biopsy shows enlarged lysosome and PAS staining. That enlargement interferes with cardiac and muscle cells ability to function. -Glucose usually normal. -Muscle biopsy would show enlarged lysosome PAS stain.
FA page 85 FA mnemonic: Vice President Can't Accept Money-> vongierke(1), Pompe(2),Cori (3), Anderson (4), McArdle (5). ABCD-> Andersen: deficient branch enzyme. Cori: deficient Debranching enzyme QID: 1023
In cori disease, the patient can't degrade branch points. Labs will show ketoacidosis and hypoglycemia. Similar, but milder sx than von gierke, but Unlike vongierke it won't have high lactate. - On biopsy you will see abnormally structured polysaccharides within the cytosol of hepatocytes.
UWQID 1030
Bacterial secretory products in toxic shock syndrome are able to bind to APCs without getting processed. That leads to easy nonspecific activation of T cells.
UWQID 15509 UWQID 676
-Negative selection occurs in the thymic medulla, where cells are kept based on low-affinity interaction with self MHC or self antigen.
UWQID 558
-Neoplastic cells can overexpress PDL1, which then bind to PD1 on the cytotoxic T cells. That's a problem because that binding inhibits the T cells from triggering apoptosis. It actually exhausts the T cells.
-Luckily, we have developped antibodies such as pembrolizumab which can act against PD1. Atezolizumab can bind to PDL1.
-UWQID 12048
-CD 14 is found on macrophages. It plays an important role in loading LPS to the ectodomain of TLR4.
-Lipid A is a major component of LPS.
-Don't confuse LPS with LOS. Lipo-oligosaccharide is on the outer membrane of N meningitidis. They are both endotoxins though, and bind to Toll-like receptors on monocytic and dendritic cells.
UQQID 738, 1598 , 1141
TNF alpha is important in leading to the systemic inflammatory response that occurs with sepsis.
UWQID 1799
If a patient's Tcells lack Il12 receptors, then they'll require treatment with interferon gamma.
-IL 12 tells a naive Th0 cell to differentiate into Th1. Without Th1 activation, there won't be interferon gamma to activate macrophages and CD8 to fight intracellular bugs.
UWQID 762
Know how mast cells are activated by cross-linking of IgE receptors. One of the substances released is tryptase.
UWQID 2068, 2069
Graft versus host disease
UWQID 1613
Lipo-oligosaccharides is found in the outer membrane of the N. meningitis bug and. is a powerful virulence factor.
-Remember that only gram negatives have an outer membrane
UWQID 738
Leukocidin is part of the PVL expressed by some staph aureus strains that can lead to necrotizing pneumonia.
UWQID 14926
Genetic reassortment of rna segments (i.e orthomyxoviruses)can lead to influenza epidemics and pandenics.
UWQID 12708
With competitive inhibition, V max will remain the same, and Km will be increased. Succinate dehydrogenase is in inner mitoch membrane, converts succinate to fumarate. Malate is a competitive inhibirot.
First aid page 233
Drugs causing hemolysis in G6pd deficiency include sulfonamide antibiotics like TMP/SMX. Others to know: dapsone, primaquine, nitrofurantoin, aspirin. First aid page 249
UWQID 894,
-Ras protein is only active when bound to GTP, unless KRAS mutation.
-Ras gene mutation can messes up the intrinsic GTPase activity-> constitutively activated ras protien leading MAPK to lead gene transcription and possibly cancer (colorectal, pancreatic)
UWQID 790
Li fraumeni syndrome occurs due to an autosomal dominant mutation in the TP53 gene. Look out for the syndrome in patients presenting with a breast mass at a young age, possible hx of osteosarcoma, and other Familly history of cancer. UWQID 345, UWQID 420
-Mutations in either the Fas receptor or Fas ligand can lead to autoimmune disease by preventing the proper function of the extrinsic pathway of Apoptosis.
UWQID 297, 298
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