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MTC 2 Last Week
cards for the last week of class
38
Anatomy
Undergraduate 1
03/04/2014

Additional Anatomy Flashcards

 


 

Cards

Term

 

 

 

One Carbon Transfer Groups

Definition
  • Tetrahydrofolate FH4
  • Vitamin B12 or cobalamin
  • S-adenoylmethionine(SAM)
Term

 

 

 

Absorption of Tetrahydrofolate

Definition
  • folate is esential vitamin absorbed by proton coupled folate transport(PCFT) SLC46A1 or reduced carrier transported SLC19A1 (SLC=Solute ligand carrier)
  • loss of PCFT of proximal thid of intestine results in anemia and diarrhea
  • folate is taken up by liver through portal vein and reconjugated with glutamate 
  • folate is reduced to tetrahydrofolate by dihydrofolate reductase 
  • N5-methyl FH4 is major blood folate transported to other tissue bound to albumin
Term

 

 

 

Oxidation and reduced form 

of Tetrahydrofolate

Definition
  • FH4 recieves one carbon from either(tryptophan, histidine, serine, glycine) 
  • involved in purine syntheses, dTMP syn and methylated VB12, and connects folate cycle to methione cycle
  • tryptophan donates formate group for purine synthesis
  • histidine donates formiminoglutamate group, closing the ring, to form an intermediate product
  • methylene tetrahydofolate reductase converts the intermediate to a methylene group to be used for dUMP to dTTP 
  • glycine and serine give methylene group for methylene tetrahydrofolate reductase to form VB12
Term

 

 

 

Recipients of FH4 Carbons

Definition
  • serine hydroxymethltransferase(major source of one carb groups in humans
  • Thymidylate synthase
  • methylene FH4 reductase
  • methionine synthase
  • dihydrofolate reductase
  • glycine cleavage enzyme
  • histidase release NH4 +
  • kynurenine formamidase
  • transformylase
Term

 

 

 

 

Absorption of VB12(cobalamin)

Definition
  • free B12 bound to haptocorrins or transcobalamin I secreted by salivary glands and stomach mucosa
  • pancreatic protease digests these and B12 binds to intrinsic factor 
  • Small intestine illium has intrinsic factor receptors
  • B12 binds to transcobalamin II in enterocyte
  • 50% of B12 is stored in liver
  • failure to absorb b12 caused by deficiency of IF causes pernicious anemia
Term

 

 

 

Reactions Requiring VB12(Cobalamin)

Definition
  • recieves methyl group from N5-methyl folate so linked to folate metabolism
  • involved in 2 reactions
  • conversion of homocysteine to methionine by methionine synthase(prevents homocystinemia associated with CardioVas disease and neurological)
  • use of propionyl-CoA to form methlmalonyl CoA that is converted to succinyl CoA by methylmalonyl CoA mutase
  • notice both pathways produce succinyl CoA
Term

 

 

 

S-Adenosylmethionine (SAM)

Definition
  • Methionine adenosyltransferase(MAT) is the rate limiting enzyme in the synthesis of SAM
  • SAM can then transfer its methyl group in numerour rx by the action of specific methyltransferase enzymes
  • this results in formation of S-adenosylhomocysteine(SAH)
  • Adenosylhomocysteine is cleaved by adenosylhomocysteine hydrolase(AHCY) to form homocysteine
  • homocysteine is converted to ietihonine by methionine synthase and cofactor VB12
Term

 

 

 

(SAM) Methyltransferase reactions

Definition
  • specific methyltransferase enzymes for conversion of each
  • epinephrine for lipolysis
  • creatine for muscle energy (glycine+ arginine then transport to liver for SAM reaction)
  • methylated nucleotides of RNA, DNA genomic imprinting, mother daughter strand recognition, gene expression
  • phosphatidylcholine in VLDL synthesis and transport
  • melatonin sleep-wake cycle (seratonin to melatonin)
  • DNA nucleotide methyltransferases being targeted for cancer treatment
Term

 

 

 

Polyamines 

Definition
  • polyamines are cations that help package DNA into nucleoids (condense euchromatin to heterochromatin) 
  • SAM functions in the synthesis of them 
  • most important polyamine are spermidine and spermine
  • SAM is decarboxylated and the propylamine groups of SAM is transferred by specific polyamine synthase to form spermidine and spermine
Term

 

 

 

Transulfation Pathway

Definition
  • homocysteine is the demthylation product of SAM
  • homocystine is converted to cysteine by cystathionine synthase and then cystathionase
  • cysteine is an important source for the synthesis of Glutathione(GSH)
Term

 

 

 

Hyperhomocysteinemia

Definition
  • caused by cystathionine synthase deficiency(converts to cystathionine)
  • no mechanism found that links the elevated levels to pathological changes
  • homocysteine cause LDL to aggregate and taken up by macrophages
  • homocysteine can cause lipid peroxidation and platelet aggregation
  • homocysteine is converted to methionine by methionine synthase and betaine methyltransferase (only exists in liver)
Term

 

 

 

Methionine Synthase

Definition
  • converts homocysteine to methionine 
  • requires both methyl donors B12 and folate to convert homocysteine
  • neural tube defect are due to variant of methylene tetrahydrofolate reductase resulting in homocystinuria
Term

 

 

 

Betaine in liver

Definition
  • can be used as a methyl group donor to homocysteine reaction to methionine in the liver
  • the liver contains the enzyme betaine methyltransferase that is not found anywhere else
  • liver also contains methionine synthase(uses FH4 and B12) so it can conduct two pathways 
Term

 

 

 

Plasma Proteins of Clinical Significance

(transport)

Definition
  • thyroxine binding globulin(thyroid hormones)
  • apolipoproteins(cholesterol, TG)
  • transferrin(iron)
Term

 

 

 

Plasma Proteins of Clinical Significance

(Humoral immunity and oncotic pressure)
Definition
  • HI: immunoglobulins
  • Oncotic pressure: albumin, proteins
Term

 

 

 

Plasma Proteins of Clinical Significance

(Enzymes and protease inhibitors)
Definition
  • enzymes: renin, coagulation factors, complement proteins
  • protease inhibitors: α1-antitrypsin (decreases with smoking)
Term

 

 

 

Liver Cirrhosis

(plasma proteins)

Definition
  • albumin decreases withile α2 increase and y-globuline increase
Term

 

 

 

Nephrotic Syndrome

(plasma proteins)

Definition
  • protein losing condition
  • loss of albumin and y-globulin with increase in αglobulin (due to α2macroglobulin)(immunoglobulins)
  • damage to glomerular basement membrane-podocytes low molecule protein loss
Term

 

 

 

Monoclonal gammopathy

(plasma proteins)

Definition
  • seen in cancers
  • decrease albumin with increase y-globulin (immunoglobulins)
Term

 

 

 

Acute-Phase Proteins

Definition
  • levels change w/i 1-2 days after surgery, infection and inflammation
  • synthesis in liver is controlled by ctokines and stress hormones
  • albumin peak is reduced while α2-globulin fraction increases mainly due to haptoglobulin(binds Hb)
  • C-reactive protein increases 100fold after bacterial infection
  • Y-globulin fraction increases in chronic disease infection, malignancies and liver cirrhosis
Term

 

 

 

Liver Function Tests

Definition
  • blood urea nitrogen
  • albumin cocentration
  • plasma protein synthesis
  • bilirubin
  • prothrombin time in coagulation
Term

 

 

 

Causes of unconjugated hyperbilirubinemia

Definition
  • hemolysis
  • Gilberts syndrome: decreased expresssion of UDP-glucuronyl transferase (transports glucuonyl to bilirubin)
  • Crigler-Najjar: total absence of UDP-glucuronyl transferase (no conjugated bilirubin)
  • Dublin-Johnson: due to decreased hepatic excretion of bilirubin because of defective ABC transporter[Organic Anion Transporter(OAT)], leading to increase urinary bilirubin excretion
Term

 

 

 

Albumin and osmotic pressure

Definition
  • determines 90% of coloidal osmotic pressure
  • has half life of 17 days present in plasma and IF and lymp but at lower conc than in plasma
  • colloidal osmotic pressure is necessary to prevent edema(happens when albumin drops below 2g/dl
  • other cause of edema include increase cap permeability, venous obstruction, impaired lymph flow, congestive heart failure
Term

 

 

 

Hyponatremia and hypernatremia

Definition
  • hypo: lower than normal (< 135 mmol/L) concentration of sodium in serum
  • hyper: higher than normal concentration of sodium in serum 
Term

 

 

 

Anion Gap

Definition
  • useful for identifying an increase in 1 or more unmeasured anions ins erum usually ketone bodies, acetoacetate
  • causes of elevation: uremia/renal failure, ketoacidosis, glycol poisoning, lactic acidosis
Term

 

 

 

5 isozymes of Lactate Dehase(LDH)

Definition
  • H(heart) and M(muslce) monomers
  • most tissues convert pyruvate to lactate while liver(M4) converts lactate to pyruvate
  • if heart form is up then myocardial infarction
  • if m4 then liver failure
Term

 

 

 

Isozymes of Creatine Kinase

Definition
  • CK-1 BB in brain
  • CK-2 HM in myocardium
  • CK-3 MM in skeletal muscle
Term

 

 

 

Microsomal Transfer Protein

(MTTP)

Definition
  • enzyme only found in liver
  • condesnes ApoB100 with phospholipids and cholesterol 
  • can account of elevated VLDL triglycerides
Term

 

 

 

Fructose Consumption

Definition
  • preferentially taken up by liver
  • uptake is not regulated by insulin
  • increases lipogenesis
  • depletes the liver of inorganic phosphates
  • reduces oxidative phosphorylation
Term

 

 

 

BCAA transaminase

Definition
  • converts valine, isoleucine, or leucine to a αketoacid
  • deficiency of this enzyme leads to maple syrup urine 
  • cofactor most likely Vitamin B6 (pyridoxal phosphate)
Term

 

 

 

 

Cortisol in Kidney vs Liver

Definition
  • cortisol in the kidney stimulates glutaminase which converts glutamine to NH3
  • cortisol in the liver stimulates glutamine synthase that synthesizes glutamine (upregulated by H, or glucocorticoids) 
Term

 

 

 

Refsum's Disease

Definition
  • defect in α-oxidation
  • alpha is used in odd chain and long branched chain FA oxidation 
  • leads to accumulation of branch chained Fatty acids that lead to neuroligical problems in infants
Term

 

 

 

Cholchicine

Definition
  • used in treatment of intercritial(middle), sub acute phase of gout
  • this phase is around day 10
  • decreases inflamatory response due to swelling and pain
  • inhibits tubulin synthesis in WBCs (prevents phagocytic activity)
  • can cause diarrhea
Term

 

 

 

Describe 3 causes of hyperuracemia

Definition
  • increased production(overproduction): tumor lysis syndrom or Lesch-Nyhan syndrome
  • decreased excretion(underexcretion): drugs(diuretics, salicylates), lead toxicity 
  • Mixed: ethanol and starvation, high fructose diet
Term

 

 

 

Describe 3 biochemical mechanisms and associated 

clinical scenarios involved in gout

Definition
  • High NADH/NAD ratio shifting LDH rx to lactate(ethanol)
  • HGPRT enzyme deficiency (lesch-Nyhan)
  • increased purine substrate converted to UA: starvation or high purine diet
Term

 

 

 

Describe 3 Clinical Phases of Gout

Definition
  • Acute: use antyinflamatory or Steroids 
  • Subacute: use colchincine, WBC membrane stabilization, inhibit tubulin synthesis
  • Chronic: decrease formation(allopurinol, febuxostat), increase removal(Urate oxidases to allontoin that is more soluble), decrease absorption of UA
Term

 

 

 

Tangier's Disease

Definition
  • yellow tounge, yellow rectal mucosa with orange-brown spots, hepatomegaly and splenomegaly 
  • autosomal codominant ABC1 mutation
  • double deletion mutation results in a frameshift and early termination in ABC1 
  • low lipoproteins, premature atherosclerosis
  • tangier's disease has low ApoA1 but no ApoA1 mutation(mutation is in transport to apoproteins)(it becomes degraded because it never forms with HDL) 
  • with out mature form of HDL, mature VLDL and chylomicrons are not formed
  • chylomicron levels can be increased in these patients(all other lipoprotein levels low)
Term

 

 

 

HDL2 and HDL3 

 

Definition
  • HDL2 is larger(TG), less dense and more protective against Coronary heart disease
  • HDL3 smaller, dense and less protective
  • HDL2 seems to be one that goes back to liver(active)
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