Non-Protein Nitrogens

why is cysteine special?

forms disulfide bonds

which amino acid is the precursor of thyroid hormone, epinephrine, and dopamine?

tyrosine

which amino acid is the precursor of serotonin and melatonin?

tryptophan

peptide bonds are formed through a ___________ rxn

dehydration rxn

amino acids are ________ in acidic solutions

positive

amino acids are _______ in basic solutions

negative

zwitter ion

a molecule which contains both positive and negative charges but is electrically neutral (@ PI)

phenylketonuria (PKU) is caused by?

deficiency in phenylalanine dehydrogenase

name that aminoacidopathy!

urine has a musty odor
brain damage (DD and microcephaly)
patient must avoid high protein foods

phenylketonuria (PKU)

what is the screening test for phenylketonuria (PKU)?

gluthrie test

describe the gluthrie test (2)

1.) petri dish w/ beta-2-thienylalanine and B. subtilis (can't synthesis phenylalanine)
2.) if the patient sample has an excess in phenylalanine, the bacteria will grow

what is the confirmation test for phenylketonuria (PKU)?

HPLC

type I tyrosinemia results for a deficiency in?

fumarylacetoacetate hydrolase (FAH)

which type of tyrosinemia results in a "cabbage odor", distended abdomen, swelling of the legs, bleeding, and failure to thrive?

type I

type II tyrosinemia results for a deficiency in?

aminotransferase (Gucci trans am is back!)

which type of tyrosinemia results in DD, tearing and photphobia, painful lesions on the soles and palms?

type II

type III tyrosinemia results in a deficiency in?

4-hydroxyphenylpyruvate dioxygenase

which type of tyrosinemia results in mild DD, seizures, and periodic ataxia?

type III

alkaptonuria results in a deficiency in?

homogentisate oxidase

name that aminoacidopathy!

dark brown urine when mixed w/ air
ochronosis (arthritis like symptoms, dark spots on the sclera)
ferric chloride makes urine turn black

alkatonuria

alkapronuria results in the build up of __________ and __________

tyrosine and phenylalanine

treatment for alkapronuria?

vitamin C

name that aminoacidopathy!

caused by a build up in branched amino acids (leucine, isoleucine, and valine)
urine with a burnt sugar odor
*my favorite aminoacidopathy*

maple syrup urine disease (MSUD)

the following symptoms are characteristics of which aminoacidopathy?

within weeks of birth lethargy, vomiting, loss of appetite, failure to thrive, severe DD, seizures, acidosis, hypoglycemia, and death if not treated

maple syrup urine disease

which aminoacidopathy prevents the metabolism of leucine?

isovaleric acidemia

name that aminoacidopathy!

prevents metabolism of leucine
urine smells like sweaty feet

isovaleric acidemia

how is isovaleric acidemia treated?

glycine and carnitine

homocystinuria is caused by a deficiency in?

cystathionine beta synthase

which aminoacidopathy results from a build up of methionine?

homocystinuria

name that aminoacidopathy!

build up of methionine
osteoporosis, dislocated lenses, and DD

homocystinuria

what is the treatment for homocystinuria?

restrict methionine; high dose of B6

which aminoacidopathy results from defective amino acid transport?

cystinuria

name that aminoacidopathy!

amino acid transport is defective
results in kidney stones of cysteine crystals --> hematuria, pain, and UTIs

cystinuria

how is cystinuria treated?

1.) dilute cysteine crystals (4L/day)
2.) penacillamine (forms soluble complexes)
3.) nephrolithotrypsy

how is cystinuria tested?

cyanide nitroprusside --> produces a red-purple color with SH groups

what are the conditions for amino acid testing? (4)

1.) fasting sample (6-8 hrs)
2.) heparinized plasma taken off cells ASAP
3.) hemolysis is unacceptable
4.) deprotonization done within 30 mins and sample tested/frozen

what is the common screening method used in amino acid testing?

TLC

which NPN accounts for most of NPN in the blood?

urea

urea can be used to assess ________ function and ________ ________

used to assess renal function and nitrogen balance

this NPN is the final product of protein metabolism

urea

how do we convert from BUN to urea?

BUN X 2.14

how does we convert BUN to mmol/L urea?

BUN X 0.36

how is urea measured?

enzymatic methods utilizing urease

what is the reference range of urea?

6-20 mg/dl

what tubes can you NOT use for a urea specimen? why?

can't use a blue or gray top tube --> urease is inhibited by citrate and fluoride
ammonium heparin also can't be used

T or F: the urine sample for urea does not need to be fresh

false; the urine isn't sterile --> bacteria have urease and breakdown urea --> leads to falsely low results

what is being measured in the urea enzymatic assay?

NADH --> NAH+ decrease in absorbance @ 340 nm

azotemia

high BUN

uremia

very high BUN

what are the different types of azotemia? (3)

1.) prerenal
2.) renal
3.) postrenal

what conditions would results in a decreased BUN? (3)

1.) nutritional deficit
2.) liver disease
3.) pregnacy

what is creatinine?

waste product from muscles

where is creatine produced?

liver

what is the function of creatine?

phosphorylated in the muscles and used as a disposable fuel

creatinine is ___________ related to GFR

inversely

why is creatinine a better marker for GFR than BUN? what are the downfalls of creatinine that make it good, but not great?

small amts are secreted and reabsorbed by the glomerulus
not sensitive enough for mild disease and concentration is a function of muscle mass, renal function, creatinine turnover, age, and gender

creatinine clearance equation

ml/min = (urine creatine X urine volume)/(plasma creatinine X time)

what are the units for creatinine clearance?

ml/min

how can we correct for the overestimation the creatinine clearance equation creates?

BSA correction (1.73/area)

BSA correction

assumes the avg size of a person

what method is used to measure creatinine?

Jaffe method

describe the Jaffe rxn (reactants and products pls)

alkaline picrate + creatinine --> red-orange chromagen

T or F: the Jaffe method is specific

false; Jaffe is non-specific --> many interferences

Jaffe method interferents that cause a positive interference (4)

1.) glucose
2.) ketones
3.) vit C
4.) pyruvate

Jaffe method interferents that cause a negative interference (2)

1.) bilirubin
2.) Hb

what is the reference method of creatinine analysis?

isotope dilution mass spec

what do we commonly use to measure creatinine?

enzymatic method w/ creatininase and peroxide

which drug causes a positive interference in the Jaffe kinetic assay?

cephalosporins

list the interferents of the Jaffe kinetic assay (2)

1.) alpha keto acids
2.) cephalosporins

what is the normal ration of BUN:creatinine?

10-20:1

describe BUN, creatinine, and BUN:creatinine in pre-renal azotemia

BUN = elevated
creatinine = normal
BUN:creatinine = elevated

describe BUN, creatinine, and BUN:creatinine in renal azotemia

BUN = elevated
creatinine = elevated (similar to BUN value)
BUN:creatinine = normal

describe BUN, creatinine, and BUN:creatinine in post-renal azotemia

BUN = elevated
creatinine = elevated (slightly)
BUN:creatinine = elevated

CHF, hemorrhage, dehydration, protein catabolism, and a high protein diet can cause which azotemia?

a.) pre-renal
b.) renal
c.) post-renal

a.) pre-rena

renal failure, AGN, and tubular necrosis can cause which azotemia?

a.) pre-renal
b.) renal
c.) post-renal

b.) renal

obstruction can cause which azotemia?

a.) pre-renal
b.) renal
c.) post-renal

c.) post-renal

what conditions can cause a low BUN:creatinine ratio? (4)

1.) decreased protein intake
2.) severe vomiting/diarrhea
3.) liver disease
4.) pregnancy

T or F: uric acid is a measure of kidney function

false; uric acid is not a measure of kidney function

uric acid is a product of __________ catabolism

purine

what is the insoluble form of uric acid found in the plasma?

urate

uric acid is metabolized to?

allantoin

high cell turnover (tumor lysis syndrome, chemo, proliferative disorders, PCV) causes which NPN to rise?

uric acid

which NPN causes gout and stones?

uric acid

what are the two methods used to measure uric acid?

1.) caraway method
2.) enzymatic method (uricase --> allatoin and perioxide)

T or F: all mammals have uricase

false; humans don't have uricase

which method of uric acid analysis involves the oxidation of uric acid in phosphotungstate (PFF)?

caraway method

what are the products of the enzymatic method of uric acid analysis? (2)

uses uricase to make allantoin and peroxide

what absorbance is used for the uricase method of uric acid analysis?

293 nm

ammonia is a waste product of?

deamination

where does most of the ammonia in the body come from?

intestinal bacteria

ammonia is converted to what substance by the liver?

urea

liver failure, Reye's syndrome, and urea cycle deficiency cause an increase which NPN?

ammonia

a build up of ammonia in the body can cause?

hepatic encephalopathy (coma)

which enzyme is used to measure ammonia? decrease or increase in absorbance?

glutamate dehydrogenase (GLDH); decrease in absorbance

which dye is used to measure ammonia?

bromophenol blue

list the specimen requirements for an ammonia specimen? (3)

1.) must be kept on ice
2.) no hemolysis
3.) smoking can also mess it up