Test Flashcards
Which amino acids are strictly ketogenic?
Leucine and Lysine
Which amino acids are strictly glucogenic?
Met, His, Val
Describe the flow of nitrogen from an amino acid to urea.
Amino Acid Nitrogen is transfered to AKG to become glutamate (by amino transferase)
- May go to glutamate dehydrogenase and be released as NH3 (which is used by carbamoyl phosphate synthase) OR
- Aspartate can put a nitrogen into the Urea Cycle on its own.
- End up as Urea
Which disease is the result of a defect of branched chain amino acid metabolism?
Maple Syrup Urine Disease
What special jobs do sulphur containing compounds do?
S-adenosylmethionine(SAM) – energy source and methyl donor
Homocysteine – vascular disease, would healing, B12 and folate metabolism
Cysteine – disulfide bonds
Tetrahydrofolate – methyl donor
Glutathione – redox buffer (protects free radical injury)
A homeless man comes to your clinic with swollen gums, mucosal bleeding, poor wound healing, and petichiae. What amino acids are defficient in this disease process?
This is scurvey a Vitamin C deficiency.
Vit C is necessary for production of hydroxyproline and hydroxylysine
A defect in Gamma-carboxyglutamate leads to what?
Decreased prothrombin. Increased bleeding.
G-glutamyl carboxylase converts Glu to Gamma-carboxyglutamate with VItamin K as a cofactor.
Which cofactor is required for aminotransferase action?
Pyridoxal phosphate (B6 or PLP)
Which mechanism of protein degradation is ATP dependant: lysosomal or ubiquination?
Ubiquitin-proteasome system is ATP dependant.
AST and ALT are liver makers used to detect damage. What are the substrates and products of each enzyme?
How are these enzymes regulated?
ALT (alanine–> pyruvate)
AST (aspartate–>oxaloacetate)
Regulated by concentrations of products and reactants
What are the reactants and products for the Urea Cycle?
3ATP + HCO3 +NH4 + asp –>
2ADP + AMP + 2 Pi + PPi + fumarate +urea
What are the sources of Nitrogen for the Urea Cycle?
Aspartate and free ammonia (carbamoyl phosphate)
How is the first enzyme of the Urea Cycle regulated?
Carbamoyl phosphate Synthase I:
Activated by N-Acetylglutamate
How is the enzyme that frees nitrogen from Glutamine regulated?
Glutamine Dehydrogenase:
+ by ADP and GTP and concentrations
- by ATP and GTP (via allosteric regulation)
- Inhibited by fed state (no protein breakdown necessary)
Which amino acids are used to transport ammonia in the blood? Which is more specific to the muscle?
- Glutamine (most tissues)
- Alanine (muscle via the Cori Cycle)
- Cori cycle uses alanine–> pyruvate–> glucose for muslce energy
Why are Lysine and leucine deemed ketogenic amino acids?
They can only be broken down into Acytyl COA and other keytone bodies (which produce no net glucose)
What are the clinical symptoms of the Urea Cycle Disorder: hyperammonemia?
. Slurring speech, asterixis (hand flapping), cerebral edema, vomitting, blurry vision.
May be caused by liver damage or enzymatic deficiencies.
Match each of the following with its proper function:
TSH, Thyroid peroxiase, Thyroglobulin (TG), Thyroxin binding globulin (TBG)
A. Oxidizes I- to I2
B. Contains Tyr residues that are iodinated to form T4,T3
C. Stimulates Iodide(I-) uptake and release of T4,T3
D. Transports T4,T3
TSH – stimulates Iodide(I-) uptake and release of T4,T3
Thyroid peroxidase oxidizes I- to I2
Thyroglobin (Tg) contains Tyr that is iodinated to form T4,T3
Thyroxin bindin globulin (TBG) transports T4,T3
How is Heme synthesis regulated? What is the building block of heme?
- Lead inhibits ALA-D and Ferrochelatase (last couple enzymes in heme synthesis)
- Heme= end product inhibition
Pyroles make up the ring structure of heme
What is the cause of neonatal jaundice. What do you expect to find?
Bilirubin glucuronyl-transferase is low in infants –> jaundice
High unconjugated Bilirubin, low conjugated bilirubin, light colored poop.
What do you expect to find in cases of hemolytic anemia?
High unconjugated Bilirubin, High conjugated bilirubin, DARK colored poop.
What is the relationship between cystine and glutathione? How does each combat oxidative stress?
- Glutathione (made of Glu, Cys, Gly) keeps heme reduced and is an antioxidant.
- Decreased in G6PD–> hemolytic anemia
- Cystine: can form disulfide bonds
Describe Met, its relation to SAM and the energy provided in SAM.
- Met is essential
- Used to produce S-adenosylmethionine (SAM)
- SAM used to produce Cys
- SAM is high energy molecule like ATP
A patient is with poor nutrition is found to have high levels of homocysteine in the blood. What is the name of the condition and how do you treat it?
Hyperhomocystinemia
Treat with B6, B12 and Folate (as it is a result of these vitamin deficiencies)
How does homocystineuria differ from Hyperhomocysteinemia?
Which amino acid(s) become essential
How do you treat homocystineuria
- Homocystineuria is a genetic defect in cystathione b-synthase deficiency (takes HC–> cystine).
- Cystine becomes essential for both
- Treat with B6, and Betanine and decrease methionine
Which vitamin is required to synthesize cysteine from homocystine?
Which vitamin is required to synthesize Methionine from homocystine?
Cystine: B6 + csytathione b-synthase (CBS)
Methionine: B12 + methionine synthase
Metionine almost has 12 letters in it. Cystine almost has 6
A patient is noted to have, kidney failure and kidney stones along with amino acids and hexagonal crystals in the urine. What caused this? How do you treat it?
Cystinuria: Defect in the renal PCT and AA transporter that transports Cystine, Ornathine, Lysine, Arginine.
Treat with Acetazolamide
What are important molecules derived from Trp?
Serotonin, Melatonin, Niacin
List two key differences between the synthesis of purine and pyrimidine nucleotides.
What are the two regulatory steps in purine synthesis?
- PRPP synthase (activates ribose by putting on a pyrophosphate P-P)
- Glutamine Phosphoribosyl pyrophosphate amiontransferase (places first nitrogen on ribose from glutamine)
How is the first step in purine synthesis regulated?
Activated by Pi (needs phosphates to add to ribose)
Inhibited by Purine Ribonucleotides
How is the second step of purine synthesis regulated?
Activated by i_ncreased PRPP_ (activated ribose)
Inhibited by AMP, GMP, IMP
When making GMP/AMP where does the energy source come from?
When making GMP/AMP, the energy source comes from what’s opposite (ie, ATP is used to make GTP and vice versa)
What is the pathway of adenosine degradation? Name the substrates and key enzymes.
A–>Inosine –>hypoxanthine–>xanthine–>uric acid
- Adenosine deaminase takes A–>I*
- Xanthine oxidase does the rest.*
Name the agent and theraputic target for gout treament.
Allopurinol
Inhibits xanthine oxidase and the formation of uric acid
A baby has been diagnosed with failure to thrive, chronic diarrhea, thrush and recurrent infections. What is going on?
This is Severe combined Immunodeficiency, most likely caused by adeonsine deaminase deficiency.
- ADA Deficiency–>
- buildup of dATP (inability to get rid of adenosine) –>
- inhibits nucleotide reductase–>
- inhibits dNTP synthesis
How do AMP and GMP degredation differ?
Adenosine is metabolized to Inosine
Guanosine is metabolized to Xanthine
Where do the carbons in purines come from?
Glutamine, Glucine and Aspartate.
Notice purines are G and A
A man comes into the ER with symptoms of mental disturbances, gout and self mutalation. What is going on here? What causes this? What is the hereditary pattern?
- This is most likely Lesch Nyhan Syndrome.
- LNS is caused by a deficiency in the HGPRT enzyme in the purine salvage pathway.
- This leads to wasting of purines and excess uric acid production.
- XR
Which drug is known to inhibit de novo purine synthesis?
6-Mercaptopurine
it caps the purine synthesis
What is the key regulated step in pyrimidine synthesis? How is it regulated
- Carbamoyl phosphate synthetase II
- makes carbamoyl phosphate–>makes orotic acid–> UMP
- Activated by PRPP (sugar)
- Inhibited by UTP (end product)
What regulates the enzyme that converts NTPs –> dNTPs?
Ribonucleotide Reductase
Activated by ATP
Inhibited by dATP (and other end products)
What is the difference between U and T? What is the source of this molecule? What inhibits this conversion?
A methyl group that comes from THF.
Regeneration of THF (dihydrofolate reductase) is Inhibited by methyltrexate (trax of methyl group)
Conversion of dUMP to dTMP is also inhibited by 5 FU (via thymidolate synthase)
Where in the pathway does dNTP synthesis branch off?
UDP
What are common symptoms/causes of Urea Cycle Disorders?
a. Infection/illness, fever, GI bleeding, vomiting, chemotherapy, surgery,
b. Postpartum
c. Intense exercise
d. Dietary protein load
e. Meds (valproate, peg asparaginase)
f. UTI (urea producing bateria)
What is the most common UCD?
Ornathine Transcarbamylase deficiency.
OTC converts ornathine to citrulline
What is important to know about OTC? Inheretance, screening, diagnostic test?
- Inheretance
- XR (only one in UCDs)
- screening
- NONE
- diagnostic test
- Orotic Acid in blood.
Which enzyme is NOT stimulated in a N acetylglutamine synthase deficiency?
Carbamoyl Phosphate Synthase I
(activated by N-Acetylglu)
How do you treat OTC def?
With a Na Benzoate or Phenylacetate.
These conjugate amino acids and make them excretable. Thus decreasing the Nitrogen in blood.
Liver transplant is curative.
What is the pathophysiology, symptoms, and Treatment of PKU?
- pathophysiology
- Dec Phenylalanine hydroylase (PAH) which makes tyrosine.
- Tyrosine=essential
- symptoms
- Musty body odor (aromatic amino acid)
- Retardation, Hypopigmentation, seizures
- Treatment
- avoid artificial sweeteners. and take tyrosine.
Describe maternal PKU
Mom doesnt have enough tyrosine while pregnant
Leads to baby with microcephaly, retardation, and heart defects.
Which amino acid is PRIMARILY respinsible for maple syurp disease?
Leucine
(but isoleucine and vialine as well)
What is the difference between Tyrosemia I and II?
TI= hepatorenal tyrosemia. T2= Oculocutaneous tyrosemia
What is the pathognominic compound in type 1 tyrosemia? How do you treat it?
Succinylacetone, which leads to hepatocellular cancer later in life.
Treat type 1 with a NTBC which basically converts type 1–>3 which is a much less toxic disease.
If you see a cherry red spot in the eye with an increased startle reflex in a baby think….
Tay Sachs
Adolescent male with acroparesthesias (pain in hadns/feet) with fevers and trunk rash. Think….
Fabry’s
Floppy baby with Left Ventricular Hypertrophy… think
Pompe (trashes the pump)
Crumpled tissue paper macrophage with HSM think…
Gaucher
Which one is sex linked Hunters or hurler syndrome?
Men hunt with good eyes (no eye probelms)
XR
When should you start feeding someone who cant feed themself in the hospital? How much should you feed them/
Normal not sick
Normal, sick
Nutritionally depleted, sick
Normal not sick: 10-14 days
Normal, sick: 5-7
Nutritionally depleted, sick: 2-5
Feed between 25cal/kg and 35 cal/kg depending on “sickometer”
A man is getting 1.2L/day of D5. He is very sick and weighs 90kg. How many calories/hr should he be getting?
Total Calories per day= 3150
-60g glucose (240 cals)
/24hrs
121.25cal/hr
What is a qualitative diet screen?
“tell me about your diet”
Focused on quality of diet.
What is the difference between EAR and RDA when it comes to diet?
Estimated Average Requirements (EAR) vs Recommended Dietary Allowance (RDA).
EAR is average intake (50% of individuals will be nourished)
RDA (95-97% will be nourished)
Describe how to begin to address dietary and lifestyle changes with a patient.
- Bringing down barriers rather than increasing motivation
- Start with diet and physical activity
- Get buy-in by asking them how they would change
What are 4 benefits of a diet rich in vegetables, fruits, whole grains, low fat dairy, healthy oils?
- Reduced mortality
- Reduced Cardiovascular disease
- Reduced blood pressure
- Less diabetes
Which malnutrition presents with muslce wasting?
Marasmus: attributed to energy deficiency
Which malnutrition presents with edema but not wasting?
Kwashiorkor due to protein deficiency
Compare and contrast energy and substrate metabolism in short term and long term starvation.
a. Glycogen stores are depleted after 1 day
b. Then the body uses fat stores (increase in ketones)
c. Finally, muscle degradation occurs leading to organ failure
State and describe 3 major nutrition problems in developing countries.
-
Maternal and child under-nutrtion – 3.1 million deaths, 45% of child deaths
- Stunting, wasting, intrauterine growth restriction
- Vit A, and Zn deficiency
- Undernutrition in pregnancy
What is the biggest thing to remember about treating malnutrition?
GO SLOWLY and think about refeeding syndrome
(ie K shift causing hypokalemia)
Name 3 Nutrition related 2015 Sustainable Development Goals (SDG).
a. Zero Hunger
b. Good health and well being
c. Clean water and sanitation
What BMI classifies someone as Obese? Waist circumfrence?
BMI 30+
Type I 30-35
Type II 35-40
Type III (morbid obesity) 40+
Waist circumfrence is +40 for men and 35+ for women
When does diabetes risk start in conjunction with BMI
In the overweight category (25-30)
What are a few main comorbitites associated with obesity?
- CVD
- OSA
- Cancer
- Orthopedic problems
- Diabetes
What are the diagnostic critera for metabolic syndrome?
3 of 5 of the following:
- Waist Circumfrence (more than 35F or 40M)
- Triglycerides (>150)
- HDL (Below 50)
- BP (130/85 or on BP drug)
- Fasting Glucose 100 or more (or on glycemic drug)
Does Excercise help with initial weight loss?
NOT really. Its more important for maintanence.
Which neurons promote food intake?
NPY (activates anabolism)
AgRP (inhibition of catabolism)
Which neurons promote satiety?
MSH (via POMC… activates catabolism)
True or false, activation of POMC inhibits the anabolic pathway.
False. Only AGrP is inhibitory
What is the effect of Ghrelin?
You Hungre..
Stimulate NPY (stimuates anabolism)
Stimulate AgRP (inhibits catabolism)
What is the effect of Leptin?
Inhibits NPY and AgRP
What is the effect of insulin?
Activates POMC–> MSH–>catabolism
Which part of the hypothalamus is the satiety center? Hunger Center?
- VenROmedial Nuclues=Satiety
- lesion makes you gROw medially
- Lateral Nucleus= Hunger
- Lesions make you lurpy (skinny)
How is BMI/obesity classified for kids?
85-95-99
Overweight - Obese - Severe Obesity
Obese children at risk for comorbitities.
What is prevention plus treatment for childhood obesity?
5 fruits/veggies
2 hrs of TV
1 hour active
All per day
What is the safest weight loss drug?
Orlistat (alli from GNC)
What are the side effects and MOA of Phentermine?
MOA: inc NE, satiety and dec food intake
SE: Nervousness, poor sleeping, headache and dry mouth (sometimes causes them to eat more)
phentermiNE
What are the side effects and MOA of Phentermine/topiramte?
MOA: Same as just phentermiNE
SE: Topiramte is teratogenic. Dry mouth, poor sleeping, nervousness etc.
What are the side effects and MOA of Lorcasarin?
MOA: Seratonin 2C angonist
SE: Heart Valve Problems
What are the side effects and MOA of Naltrexone/Buproprion?
MOA: Opioid agonist + Dop/NE reuptake inhibitor
SE: Suicidal ideation, seizures, inc BP
What are the side effects and MOA of Liraglutide?
MOA: GLP1 agonist,
SE: Not discussed
Which antipsychotics do NOT cause weight gain?
Ziprasidone and apripriazole (think of the anti z ychotics)
What is the order of effectiveness for gastric sugery?
Band then Sleeve than Bypass
What are the requirements for MEds/Surgery recommendation for obesity?
Meds 30 BMI or 27+ CM
Sur: 40BMI or 35 + CM
What is the purpose of stages of change?
Diagnostic but does not change treatment or change behavior.
Describe two important steps in “Values‐based counseling.”
- Identifying core values
- Relating core values to health behavior to be addressed
Identify the key criteria addressed in the “health belief model.”
A person’s willingness to change relates to their perception of vulnerability for illness and effectiveness of treatment
How is Iron regulated in comparison to zinc?
Iron is regulated via absorption. There are no regulations for getting rid of iron (bleeding and sluffing of cells)
Zinc: Absorption AND excretion
Whats the best source of iron?
Meat
How is iron stored?
In the Fe, tin (ferritin)
Iron deficiency leads to what kind of anemia?
Microcytic
What physical exam findings are consitend with zinc deficincy?
Dermatitis, stunting, anorexia, hypogonadism, poor wound healing
A breastfed newborn comes in with rickets and bone problems and lives in Alaska, what do you think?
Vit D def.
A breastfed newborn comes in with rickets and bone problems and lives in Alaska (low sun)
A patient has night blindness, dry scaly skin, and infections. What do you suspect?
Vit A def.
A newborn has impaired clotting times. What vitamin is def?
K for klotting.
Which fat soluble deficiency is associated with neurologic symptoms?
Vitamin E
Presentation similar to B12 def but w/o anemia
A 6 month old breastfed infant, vomiting opthalmoplegia and heart faliure. Whats the dx?
Wet Beri Beri (B1 or thiamine def)
Thiamin def= Neuro Symptoms + CHF
Thiamin affects The Heart
A 5 yr old child eats only burgers and milk, not limping and refusing to walk, has a rash. Whats the Dx?
Scurvy
Does not eat many fruits or veggies.
“eats only one food group”
Effects tons of body systems because of collagen.
An alcoholic “found down” w altered mental status, anemic. Dx?
Wernicke Korsakoff (from B1 or thiamine def)
Obese adolescent s/p bariatric surgery. Cant walk and fals down. Whats going on?
Think B1 for bariatric surgery.
Dry beri beri impairs motor fxn and reflexes.
Adult with diarrhea and rash on hands head and neck (dermatitis). Think…
Niacin (B3) def.
Pellagra:
i. Dermatitis (symmetric aggravated by sun/heat, pellegra)
ii. Dementia
iii. Diarrhea
iv. Death
Sores in mouth (or cracked lips) and increased vascularization of conjunctiva
B2 def
NT Defects, Macrocytic anemia, hypersegmented PMNs w/o neurological symptoms
Folate def.
Hypersegmented PMNs with neurological symptoms
B12
Review of Vitamin Deficiency findings
What are the 4 Statin Benefit groups?
- Primary prevention: Diabetes, 40-75 years, LDL-C +70
- Primary prevention: No diabetes, Same as above + 7.5% risk
- LDL> 190 without cause
- Secondary prevention: previous CVD
What is a genetic cause of high HDL?
CTEP deficiency
Protective against CVD
The laboratory data on a patient brings with him include a fasting lipid panel. This reveals a total cholesterol of 250 mg/dl, a triglyceride level of 335 mg/dl, and an HDL cholesterol of 33 mg/dl. What is his LDL?
LDL= Total - HDL- TGs/5
LDL= 150 mg/dl
A patient presents with pancreatitis, puritic xanthomas (zit things) and a creamy supernatant layer on blood centrifuge. What is the problem?
Hyperchylomicronemia
Lipoprotein lipase or apolipoprotein C-II deficiency (lipoprotein lipase cofactor)
