Cell Bio 4

Question 1

what to do w/ excess aa?

Answer 1

aa = not stored –> free pools; excess = converted to glu then sat fat/chol or elim from body; choose lean meat over processed

Question 2

pos vs neg nitrogen balance

Answer 2

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

Question 3

AST/ALT

Answer 3

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

Question 4

glutamine cycle

Answer 4

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

Question 5

glucose-alanine cycle

Answer 5

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

Question 6

carbamoylphosphate synthetase I (CPS I) vs ornithine transcarbamoylase (OTC) vs arginase

Answer 6

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

Question 7

defects in any urea-cycle enzyme result in what?

Answer 7

elevated glutamine and NH3 (hyperammonemia), also unable to synthesize urea (low BUN)

Question 8

how is urea cycle regulated?

Answer 8

substrate availability: high NH3 prod –> high urea prod; high arg –> high N-acetylglutamate (NAG) –> high CPS I –> high ornithine

Question 9

Know graph in Lecture 33, Slide 18

Answer 9

KNOW IT

Question 10

What’s the most common lab value to test pt’s urea cycle?

Answer 10

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

Question 11

why are aa deaminated before degradation?

Answer 11

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

Question 12

which aa = exclusively ketogenic?

Answer 12

lys and leu

Question 13

how to remove amine group from aa?

Answer 13

transamination and deamination oxidation

Question 14

explain phe to tyr and how it relates to PKU. what is benign hyperphealanemia?

Answer 14

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

Question 15

What enzyme, if deficient, could affect tyrosine synthesis from phenylalanine and disrupt catecholamine synthesis?

Answer 15

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

Question 16

alkaptonuria

Answer 16

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)

Question 17

maple syrup urine disease

Answer 17

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

Question 18

What is the cause of primary oxaluria type I? What amino acid pathway is involved?

Answer 18

Caused by deficiency of transaminase in liver peroxisomes→excess oxalate→oxalate stones, kidney damage
Defect in glycine degradation to form pyruvate

Question 19

What is the composition of the glutathione tripeptide and what does it do in cells?

Answer 19

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)

Question 20

If a patient has a deficiency in dihydropteridine reductase, what synthesis reactions would be affected?

Answer 20

can’t make BH4 from BH2, can’t make serotonin from tryptophan, can’t make dopamine, nor/epi (catecholemines), or melatonin

Question 21

Which enzyme acts to inactivate catecholamines, neurotransmitters and phenylethylamines?

Answer 21

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

Question 22

What amino acid is used to make the neurotransmitter serotonin?

Answer 22

trp

Question 23

What is albinism and what is the enzyme deficiency?

Answer 23

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

Question 24

Know creatine vs creatinine

Answer 24

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

Question 25

What is a porphyria?

Answer 25

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

Question 26

What heme synthesis enzyme or enzymes is/are inhibited by lead?

Answer 26

Lead inhibits delta-ALA dehydratase (cyto enzyme) and ferrochelatase (mito enzyme) –> dec heme –> anemia
Let me get dryh and ferril

Question 27

Know homocystinuria I vs II vs III. Know tetrahydrofolate, Vitamin B12 and S-adenosylmethionine with them

Answer 27

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

Question 28

how to convert dUMP to dTMP. What cofactors / enzymes are needed for this reaction? What are two common inhibitors of this process?

Answer 28

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.

Question 29

What are sulfa drugs and why are they bad for bacteria but OK for humans?

Answer 29

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

Question 30

What are two major reactions that Vitamin B12 participates in directly? How do Vitamin B12 and tetrahydrofolate interact normally and what is exchanged?

Answer 30

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

Question 31

What can happen to tetrahydrofolate if a person has a Vitamin B12 deficiency?

Answer 31

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

Question 32

What is methylmalonyl CoA mutase and why is it important?

Answer 32

Methylmalonyl CoA mutase = enzyme that converts L methylmalonyl CoA to succinyl CoA; important for making TCA intermediates

Question 33

Recognize common molecules that are produced using S-adenosylmethionine (SAM) as a cofactor.

Answer 33

SAM converts precursor to methylated product: Epinephrine, creatine, methylated nucleotides, phosphatidylcholine, melatonin. Lecture 36, Slide 24

Question 34

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).

Answer 34

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

Question 35

Why is the molecule 5’-phosphoribosylpyrophosphate (PRPP) necessary for purine synthesis?

Answer 35

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

Question 36

What is carbamoylphosphate synthetase II and its function in pyrimidine function?

Answer 36

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)!

Question 37

What are the two purine salvage enzymes by name? What is the goal of purine salvage?

Answer 37

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

Question 38

how are the purine and pyrimidine pathways regulated?

Answer 38

Purine Regulation: Product inhibition, Feedback inhibition (AMP feedback)
Pyrimidine: Feedback inhibition-UTP inhibits, PRPP induces

Question 39

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?

Answer 39

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)

Question 40

What are some typical sources of nitrogen that is taken up by the urea cycle?

Answer 40

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

Question 41

most [O] vs most [H] C

Answer 41

N10-formyl-FH4 vs N5-methyl-FH4. formyl > methenyl > methylene > methyl

Question 42

Abetalipoproteinemia (aka Bassen Kornweigh Syndrome)

Answer 42

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

Question 43

how to manage PKU in infants vs moms vs adults?

Answer 43

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

Question 44

HBV and common “whole proteins” in foods

Answer 44

easily utilized by the body; foods that lead to efficient absorption.
Wheat - glutenin, gliadin
Milk – casein, whey
Corn – zein
‘soy protein isolates or extracts’

Question 45

how to reduce CVD risk?

Answer 45

Reducing: LDL, BP, and Body weight
Increasing: insulin sensitivity, heart strength, and coronary artery size and tone

Question 46

3 metabolic systems supply energy: creatine phosphate vs anaerobic glycolysis vs aerobic resp/[O] phosphorylaation

Answer 46

for quick short burst exer vs short high intensity exer (10min) vs endurance exer; use fat over glu; training inc size and # of mito

Question 47

how to estimate energy needs?

Answer 47

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

Question 48

indirect calorimetry (GOLD STANDARD)

Answer 48

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

Question 49

predictive eqns for gen pop vs critically ill

Answer 49

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)

Question 50

how to eval nutrition status: ABCDE

Answer 50

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

Question 51

Identify the necessary measures that need to be monitored and evaluated following MNT

Answer 51

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

Question 52

Recall the current recommendation for macronutrient distribution for general health

Answer 52

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

Question 53

Interpret the scientific-basis for macronutrients recommendations.

Answer 53

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

Question 54

how to maintain vs lose LBM?

Answer 54

adeq protein intake, maintain aa pool, inc protein synthesis, RESISTANCE EXER vs protein malnutrition, stress response to wound/dz

Question 55

2 phases of metabolic stress: ebb phase vs flow phase

Answer 55

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

Question 56

hormones and proteins involved in proteolysis

Answer 56

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

Question 57

how does body handle starvation?

Answer 57

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

Question 58

how does body handle burns?

Answer 58

First 24-28hrs should focus on fluid resuscitation
Minimize metabolic stress response
High energy, high protein nutrition therapy
Prevent stress ulcer