Cell Bio 4 Flashcards
what to do w/ excess aa?
aa = not stored –> free pools; excess = converted to glu then sat fat/chol or elim from body; choose lean meat over processed
pos vs neg nitrogen balance
amt nitrogen excreted < amt consumed –> low BUN –> growth, hypothyroid, tissue repair, pregnancy vs amt of nitrogen excreted > amt consumed –> high BUN –> fasting, burns, wasting, fevers, tissue injury, malnutrition
AST/ALT
asp aminotransferase, ala aminotransferase; intracellular enzymes nmlly low in plasma, if high –> liver dz (cirrhosis, viral hepatitis, circulatory collapse, cell necrosis); measured by liver fxn tests
glutamine cycle
in muscle/peripheral tissue cell: alpha KG + free ammonium (NH4+) makes glutamate via GDH + NADPH → glutamate + NH4+ makes glutamine via glutamine synthetase + ATP → transferred to liver→liver breaks it down back to glutamate + NH4+ via glutaminase → breaks glutamate down to alpha KG + NH4+ via GDH –> the 2 NH4+ = excreted in urine as urea
Gets rid of excess nitrogen in muscle to eventually be able to excrete
glucose-alanine cycle
muscle transfers ammonia from aa to glutamate + alpha keto acid –> glutamate transfers ammonia to pyru (from glycolysis) –> make ala –> ala = transferred to liver to be used to make glucose for muscle to take up &/OR make nitrogen for liver to excrete as urea
Carbon from alanine= glucose
Nitrogen from alanine = urea→ urine
Pyruvate and ala = transamination pairs
carbamoylphosphate synthetase I (CPS I) vs ornithine transcarbamoylase (OTC) vs arginase
NH3 + bicarbonate + 2 ATP –> carbamoyl phosphate; in mito; rate limiting step of urea cycle vs transfers carbamoyl of carbamoyl phosphate to ornithine –> citrulline and Pi; in mito vs hydrolyzes arg to ornithine and urea; in cyto; final step of urea cycle
defects in any urea-cycle enzyme result in what?
elevated glutamine and NH3 (hyperammonemia), also unable to synthesize urea (low BUN)
how is urea cycle regulated?
substrate availability: high NH3 prod –> high urea prod; high arg –> high N-acetylglutamate (NAG) –> high CPS I –> high ornithine
Know graph in Lecture 33, Slide 18
KNOW IT
What’s the most common lab value to test pt’s urea cycle?
Blood Urea Nitrogen (BUN) allows pt to assess function of urea cycle: Low BUN→not synthesizing urea (or synthesizing less urea in case of positive nitrogen balance)
Blood ammonia levels chks urea cycle function → hyperammonemia (increased blood ammonia levels); 2 types of hyperammonemia = acquired (liver damage) or congenital (inherited)
Elevated AST/ALT
why are aa deaminated before degradation?
their carbon skeleton can be used to make intermediates for either glucogenic (pyru, TCA intermediates –> gluconeo substrates) or ketogenic (acetoacetate, acetyl CoA, acetoacetyl-CoA) paths, or to make another type of aa w/ same backbones; carb skeleton can also become CO2
which aa = exclusively ketogenic?
lys and leu
how to remove amine group from aa?
transamination and deamination oxidation
explain phe to tyr and how it relates to PKU. what is benign hyperphealanemia?
phe = hydroxylated to make tyr via phenylalanine hydroxylase + BH4 + O2; BH4 = [O] to BH2 in rxn and must be [H] back to BH4 for phe hydroxylase to keep working. PKU = defic in PAH –> hyperphenalanemia (classical), or defic in dihydropteridine reductase or enzymes for BH4 –> high phe despite nm PAH (malignant/atypical) (can control it by diet but still not effective –> death by 2 y/o). Goal: reduce phe and inc tyr supplement,
involves biopterin synthetase
What enzyme, if deficient, could affect tyrosine synthesis from phenylalanine and disrupt catecholamine synthesis?
Deficient PAH, which catalyzes conversion of Phe→Tyr, could also disrupt catecholamine synthesis b/c Tyr is a precursor molecule of catecholamines
Deficient DHPR, which converts BH2 to BH4, disrupt Tyr synthesis
alkaptonuria
inherited genetic defic of homogentisate oxidase –> accumulation in homogentisic acid (HGA) in skin and tissue –> dark pigment and urine
Related to PKU and Tyrosinemia; results of inherited deficiencies of Phe and Tyr (AA that form fumarate)
maple syrup urine disease
BCAA like Ile, Leu, Val undergo transamination via BCAA aminotransferase + B6 to be alpha keto acid –> alpha keto analogs become [O] decarboxylated via branched chain alpha keto acid dehydrogenase (BCKD) complex to be degraded and make NADH/FADH2; error in BCKD –> sweet smelling urine and neuro problems; used as genetic and blood diagnostic test
What is the cause of primary oxaluria type I? What amino acid pathway is involved?
Caused by deficiency of transaminase in liver peroxisomes→excess oxalate→oxalate stones, kidney damage
Defect in glycine degradation to form pyruvate
What is the composition of the glutathione tripeptide and what does it do in cells?
Tripeptide composed of glutamate, cysteine, and glycine
Synthesized in two steps (1) gamma-glutamylcysteine synthase and (2) glutathione synthase (all non-essential amino acids)
Removes H2O2 out of cell (protects against oxidative damage)
If a patient has a deficiency in dihydropteridine reductase, what synthesis reactions would be affected?
can’t make BH4 from BH2, can’t make serotonin from tryptophan, can’t make dopamine, nor/epi (catecholemines), or melatonin
Which enzyme acts to inactivate catecholamines, neurotransmitters and phenylethylamines?
catecholamines = inactivated by oxidative deamination catalyzed by monoamine oxidase (MAO) and by O-methylation by catechol-O-methyltransferase (COMT)
MAO-A = deaminates norepinephrine and serotonin
MAO-B = acts on phenylethylamines
What amino acid is used to make the neurotransmitter serotonin?
trp
What is albinism and what is the enzyme deficiency?
lack of pigmentation in the skin, hair, eyes, and sensitivity to sunlight. Caused by defective Cu-dependent tyrosine hydroxylase (of melanocytes) or other enzymes that convert tyrosine to melanin
Know creatine vs creatinine
creatine phosphate = high energy molec vs cyclic cmpd after phosphate spont cleaves off, can’t be further metabolized –> excreted thru urine.
amt of creatinine excreted = proportional to creatine phosphate –> tells muscle mass, and = constant daily –> nml renal fxn. high blood creatinine –> kidney malfxn, high serum creatinine –> glomerular dysfxn
What is a porphyria?
Group of rare inherited/acquired defects in heme synthesis –> accumulation and increased excretion of porphyrins or porphyrin precursors; can result in toxic intermediates –> ROS; porphyrins readily bind to metal ions
What heme synthesis enzyme or enzymes is/are inhibited by lead?
Lead inhibits delta-ALA dehydratase (cyto enzyme) and ferrochelatase (mito enzyme) –> dec heme –> anemia
Let me get dryh and ferril
Know homocystinuria I vs II vs III. Know tetrahydrofolate, Vitamin B12 and S-adenosylmethionine with them
defic in cystathionine B-synthase/B6 –> defect in transsulfuration; can’t make homocysteine vs defic in methyl-B12/cobalamin synthesis –> defect in transmethylation vs defic in N5-methyl-FH4 synthesis –> defect in transmethylation. all have high homocysteine and low methionine; SAM, THF, B12 = methyl group donors
how to convert dUMP to dTMP. What cofactors / enzymes are needed for this reaction? What are two common inhibitors of this process?
ser to methylene FH4 (vit B9) –> methylene FH4 + dUMP to dihydrofolate (FH2) + dTMP via Thymidylate Synthase –> FH2 to FH4 via dihydrofolate reductase + NADPH
Drugs: (anticancer)
5-Fluorouracil inhibits thymidylate synthase by mimicking dUMP (competitively inhibits for dUMP and FH4 binding)
Methotrexate is a folate analog that is a competitive inhibitor for dihydrofolate reductase –> prevent regeneration of fully reduced FH4 needed to make dTMP.
What are sulfa drugs and why are they bad for bacteria but OK for humans?
aka Antibacterial sulfonamides; synthetic antimicrobial agents that contain the sulfanamide group –> tx bacterial infxns
safe for humans b/c we cannot synthesize folate, while bacteria must
Sulfa drugs = PABA analogs –> disrupt folate synthesis in bacteria by competitively inhibiting dihydropteroate synthetase (DHPS) (converts PABA→folate) –> prevent bacterial growth and cell division
What are two major reactions that Vitamin B12 participates in directly? How do Vitamin B12 and tetrahydrofolate interact normally and what is exchanged?
1) N5-methyl-FH4 RECEIVES a one-carbon group that is reduced to the methyl level and IS TRANSFERRED to B12 to make methylcobalamin –> methylcobalamin transfers methyl group to homocysteine –> homocysteine converts to methionine –> methionine = activated by SAM to transfer methyl group; tetrahydrofolate and B12 work together on methyl transfer reactions
2) Rearrangement of L-methylmalonyl-CoA to make succinyl-CoA via methylmalonyl CoA mutase + B12
What can happen to tetrahydrofolate if a person has a Vitamin B12 deficiency?
methyl trap hypothesis: Nearly all FH4 will accumulate in the methyl-FH4 form–methyl trap –> no free FH4 for dTMP synthesis (for nucleotide synthesis); can’t convert methylmalonyl CoA to succinyl CoA for myelin formation; can’t convert homocysteine to methionine; folate levels drop too b/c it is trapped in accumulated N5-methyl→ megaloblastic anemia
i..e., B12 deficiency→folate deficiency
What is methylmalonyl CoA mutase and why is it important?
Methylmalonyl CoA mutase = enzyme that converts L methylmalonyl CoA to succinyl CoA; important for making TCA intermediates
Recognize common molecules that are produced using S-adenosylmethionine (SAM) as a cofactor.
SAM converts precursor to methylated product: Epinephrine, creatine, methylated nucleotides, phosphatidylcholine, melatonin. Lecture 36, Slide 24
For the synthesis of purines vs pyrimidines, recognize the starting materials (i.e., ribose-5-P for purines and glutamine for pyrimidines) and the “goal” molecules of each pathway (i.e., IMP for purines and UTP for pyrimidines).
ribose 5 phosphate + ATP –> PRPP; precursors: R5P, ATP, gly, gln, asp, CO2, N10-formyl-FH4 vs gln + CO2 –> carbamoyl phosphate –> carbamoyl phosphate + asp –> oroate + R5P –> OMP deCO2 to UTP; precursors: gln, CO2, asp
Why is the molecule 5’-phosphoribosylpyrophosphate (PRPP) necessary for purine synthesis?
PRPP (5-Phosphribosyl 1-Pyrophosphate) synthesis = starting point of de novo purine synthesis
PRPP = the activated form of ribose
Synthesized from ribose 5’-phosphate and ATP
What is carbamoylphosphate synthetase II and its function in pyrimidine function?
catalyzes the synthesis of carbamoyl phosphate from glutamine in 1st step of pyrimidine synthesis
NOTE: don’t mix up CPS I (from urea cycle) and CPS II (pyrimidine synthesis)!
What are the two purine salvage enzymes by name? What is the goal of purine salvage?
Salvage pathways-way to recycle bases/nucleosides from DNA/RNA degradation –> Goal: To save ATP and avoid excess hypoxanthine/xanthine. Can be reused after this bc they’re converted to nucleoside triphosphates.
Free bases react w/ PRPP to make nucleotides: guanine/hypoxanthine to GMP/IMP via Hypoxanthine-guanine phosphoribosyltransferase (HGPRT); adenine to AMP via Adenine phosphoribosyltransferase (APRT); Adenosine (a nucleoside) can become AMP via adenosine kinase + ATP→it is the only salvaged purine
how are the purine and pyrimidine pathways regulated?
Purine Regulation: Product inhibition, Feedback inhibition (AMP feedback)
Pyrimidine: Feedback inhibition-UTP inhibits, PRPP induces
What is gout and what purine degradation molecule causes it? What enzyme forms that molecule – and what pathway produces the molecule? Is there a drug molecule that can inhibit the key enzyme in the pathway that makes the molecule responsible for gout? Any diet changes?
high uric Acid causes gout. Xanthine oxidase from purine degradation [O] hypoxanthine to xanthine –> [O] xanthine to uric acid in joints; from inc xanthine dehydrogenase activity; salvage pathways with HGPRT and APRT prevent too much xanthine/ hypoxanthine. Allopurinol inhibits xanthine oxidase → accumulation of hypoxanthine and xanthine (more soluble than uric acid → less inflammation). dec purine intake (meat, seafood, alc); inc low fat dairy, ascorbic acid, wine (alkaline ash effect)
What are some typical sources of nitrogen that is taken up by the urea cycle?
AA: Transamination rxns (provide NH3 and Asp), Oxidative deamination (provide NH3 and Asp), Transporting NH3 (ammonia) to liver
Waste Nitrogen from other sources: Purine nucleotide cycle (brain, muscle) & gut bacteria
most [O] vs most [H] C
N10-formyl-FH4 vs N5-methyl-FH4. formyl > methenyl > methylene > methyl
Abetalipoproteinemia (aka Bassen Kornweigh Syndrome)
auto rec d/o; Fat and fat-soluble vitamin malabsorption d/t reduced chylomicron formation –> cannot synthesize lipoproteins containing Apo lipoprotein B→ gets stuck inside enterocytes
Mutation in the microsomal triglyceride transfer protein
how to manage PKU in infants vs moms vs adults?
phe-free formula w/ reg formula or breast milk –> still give 90% protein and 80% energy; low phe foods for development and energy needs; blood phe control benchmark = 2-6 mg/dL; education about therapy and psychosocial development vs mom’s lvls controls baby’s lvls in utero; after baby born –> baby loses lvls –> quick defic; high maternal blood lvls can cause cardiac defects, stunted growth, microcephaly, mental incapacities –> fam and prof support vs tx early for less neuro dmg; low phe diet throughout life; may need mental support; measure progress by IQ
HBV and common “whole proteins” in foods
easily utilized by the body; foods that lead to efficient absorption.
Wheat - glutenin, gliadin
Milk – casein, whey
Corn – zein
‘soy protein isolates or extracts’
how to reduce CVD risk?
Reducing: LDL, BP, and Body weight
Increasing: insulin sensitivity, heart strength, and coronary artery size and tone
3 metabolic systems supply energy: creatine phosphate vs anaerobic glycolysis vs aerobic resp/[O] phosphorylaation
for quick short burst exer vs short high intensity exer (10min) vs endurance exer; use fat over glu; training inc size and # of mito
how to estimate energy needs?
indirect calorimetry (metabolic cart; CO2/O2) - measures inspired and expired gas vol; very expensive and need strong technical expertise to get accurate results. predictive eqns - alternative to indirect calorimetry; inaccurate –> inc risk of over/underfeeding
indirect calorimetry (GOLD STANDARD)
analyzes rate of CO2 prod and O2 consumption; resp quotient (RQ) aka resp exchange ratio (RER) = vol of CO2 and vol O2; high protein diet –> 0.8, high fat –> 0.7, high carb –> 1; RQ outside of 0.7-1.0 –> unusual metab or resp conditions, failure to adhere to fasting requirement, or equipment error –> rpt measurement
predictive eqns for gen pop vs critically ill
factors sex, age, wt, ht; Harris-Benedict, Mifflin-St Jeor (obese/overwt), WHO/FAO/UNU/Schofield vs Penn State (Mifflin, body temp, vent rate; <60yo), modified Penn State (Mifflin, body temp, vent rate; >60yo), Swinamer (body temp, SA, TV; if indirect calorimetry = unavail and mechanically ventilated), Ireton Jones (sex, age, wt, trauma/burn, obesity; if indirect calorimetry = unavail and ventilated dep; if obese –> hypocaloric regimen)
how to eval nutrition status: ABCDE
Anthropometric (ht, wt, circumference, body composition), Biochemical (blood, urine, hair analysis), Clinical (hair loss, thirst, skin pinch, discoloration), Diet (compare/contrast, self report but beware of bias), Economics/Emotions/Education
Identify the necessary measures that need to be monitored and evaluated following MNT
Dietician: adjust and document nutrition care plan and orders
Nurse: monitor and document changes in intake, weight, and function
Physician: continue nutrition care coordination
Is pt meeting/maintaining goals?
Ensure that understanding and implementation of intervention is progressing
Recall the current recommendation for macronutrient distribution for general health
carbs = 130g/d based on glu utilization by brain; fiber = 38g/d M, 25g/d F; protein = 56g/d M, 46g/d F based on nitrogen equil; linoleic acid/omega 6 EFA = 17g/d M, 12g/d F; alpha linoleic acid/omega 3 EFA = 1.6g/d M, 1.1g/d F
Interpret the scientific-basis for macronutrients recommendations.
Estimated Energy Requirements (EER) = average dietary energy intake to maintain energy balance in a healthy adult of a defined age, gender, weight, height, and level of physical activity, consistent with good health. Recall that adults need 25-30kcal/kg/day
Average Macronutrient Distribution Range = range of intakes for particular energy source that is assoc. w/ lowered risk of chronic disease while providing adequate intakes of essential nutrients
Protein: 10-35% of energy
Carbs: 45-65% of energy
Fat: 20-35% of energy
how to maintain vs lose LBM?
adeq protein intake, maintain aa pool, inc protein synthesis, RESISTANCE EXER vs protein malnutrition, stress response to wound/dz
2 phases of metabolic stress: ebb phase vs flow phase
immediate/24-48hr, dec BMR, lactic acidosis, shock, tissue hypoxia vs body uses energy stores, activate innate immune system, maintain O2 transport and fluid resuscitation
hormones and proteins involved in proteolysis
Glucagon→gluconeogenesis, protein catabolism –> AA uptake –> ureagenesis
Cortisol→skeletal muscle catabolism, increased haptic use of AAs for gluconeogenesis, glycogenolysis, and acute phase protein synthesis
Acute phase proteins→rapid loss of LBM, increased net N balance
Altered lipid metabolism→ increased lipolysis→increased FFA
Cytokines→regulate injury response
how does body handle starvation?
Adaptive phase: decreased protein catabolism and hepatic gluconeogenesis
First day: glucose from glycogenolysis
After day 1, glucose from gluconeogenesis
Lipids metabolized
Continued fast: FFA→ketones
how does body handle burns?
First 24-28hrs should focus on fluid resuscitation
Minimize metabolic stress response
High energy, high protein nutrition therapy
Prevent stress ulcer
