Lecture 25+26

Question 1

PKU generally

Answer 1

common (but rare)
autosomal recessive disorder
determined by mass spec.

responds well to treatment of low Phe diet
low protein, no eggs/milk/meat
no aspartate

can live normal life if following diet

Question 2

biochemical defect in PKU

Answer 2

no phenylalanine hydrolase enzyme

thus more phenylalanine and less tyrosine

build up of phenylpyruvic acid
need tyrosine in diet

Question 3

signs of PKU

Answer 3

delay milestones
low IQ
mousy odor of urine (due to Phe metabolite build up)

Phe levels are high in blood

decreased pigmentation of skin and hair
tyrosine conversion to melanin is inhibited by high phe levels; inhibits tyrosinase

Question 4

Treatment for those with PKU

Answer 4

dietary treatment- avoid phenylalanine

sapropterin (synthetic form of BH4)
typically for mild or moderate forms of disease
mutant from of enzyme that has low affinity for BH4
first non-diet treatment considered

Question 5

maternal PKU syndrome

Answer 5

women with PKU must maintain low levels of Phe before conception and pregnancy

high maternal blood levels of Phe:
microcephaly
lack of mental development
congenital heart defects

elevated Phe has teratogenic properties!!
does not matter if fetus has PKU or not

Question 6

alkaptonuria

Answer 6

homogentisic acid oxidase deficiency
build up of homogentisic acid

dietary restriction of Phe and tyrosine may reduce the deposits of homogentisic acid

Question 7

alkaptonuria signs

Answer 7

darkening of the urine on standing
discoloration of the cartilage and connective tissues
(ochronotic pigment)
leads to arthritis

these symptoms are due to the oxidation of homogentisic acid

Question 8

tyrosinemia type I

Answer 8

build up of fumaryl acetoacetate
leads to kidney and liver damage
cabbage-like smell of the urine

Question 9

tyrosinosis or tyrosinemia type I

Answer 9

inborn error of phenylalanine tyrosine metabolism

seen to have a fumarylacetoacetate hydrolase deficiency

liver and kidney failure
cabbage smell to urine

dietary restriction of phe and tyr
difficult to accomplish

Question 10

maple syrup urine disease (MSUD)

Answer 10

symptoms occur in neonates aged 4-7 days
can be detected by neonatal screening

signs/symptoms: 
poor feeding
vomiting
lethargy 
seizures 
ketosis (sweet smell of urine) 
coma / death if not treated

Question 11

biochemical defect in MSUD

Answer 11

cannot break down branched chain amino acids

No Branched chain α-keto acid dehydrogenase

thus build of of branched amino acids

Question 12

treatment for MSUD

Answer 12

No intake of leucine, isoleucine, or valine
improves neurological functions

difficult to treat
BCAA found in most protein sources and are essential

dietary supplementation of B1 in those that have a low affinity enzyme

regular checking of BCAA in blood

Question 13

Methylmalonyl CoA mutase deficiency

Answer 13

results increased levels of methylmalonic acid in circulation

will lead to metabolic acidosis
can have seizures and encephalopathy

sometimes have improvement with B12 supplementation

Question 14

homocystinuria

Answer 14

defect in the metabolism of homocysteine
high plasma and urinary levels of homocysteine

due to a deficiency in cystathionine Beta synthase (transulfuration pathway)

Question 15

homocystinuria signs/symptoms

Answer 15

homocysteine can bind to connective tissues and disrupt structure

dislocation of lens (after age 3) 
skeletal abnormalities 
osteoporosis 
delay in mental development 
premature arterial disease (lipid deposits) (lipid oxidation and platelet aggregation) 

may respond to vit B6 supplement

Question 16

general composition of pancreatic secretions

Answer 16

same Na and K as plasma - isotonic
high HCO3 concentration (alkaline)
Low Cl-

enzymes:
lipase, amylase, proteases

rate:
low flow: mostly Na and Cl
high flow: mostly Na and HCO3
both isotonic

Question 17

secretin secretion

Answer 17

secreted from S cells from duodenum
in response to H+ in lumen

leads to increased HCO3

Question 18

CCK secretion

Answer 18

secreted from the I cells in the duodenum

in response to small peptides, AA’s, and fatty acids

effect:
increased enzyme secretion
increased HCO3 secretion

Question 19

ACh secretion

Answer 19

secreted from vagus terminals

in response: H+, small peptides, AA’s, FA’s

effect:
increased enzyme secretion and increased HCO3 secretion

Question 20

pancreatic acinar cells

Answer 20

low volume, NaCl, and enzymes secretions

a rise in Ca triggers secretions

Question 21

pancreatic ductal cells

HCO3, Cl, Na, H20, and H+

Answer 21

modifies: absorbing Cl-, secreting HCO3 via Cl-HCO3 exchanger

HCO3 produced by carbonic anhydrase

Cl diffuses by CFTR channel
NKCC transporter provides Cl too

Na and H2O:
passively move by para-cellular pathway

H+:
formed with HCO3 in the cell
exits across basolateral membrane via Na-H exchanger

Question 22

Low flow and high flow?

Answer 22

Low flow:
from acinar cells
mainly NaCl

High flow:
from ductal cells
mainly NaHCO3

Question 23

cystic fibrosis and pancreatic secreting cells

Answer 23

defective CTFR channel

less Cl- secretion 
lower lumen negativity 
decreased Na and H2O movement 
decreased ductal secretions 
decreased enzyme secretion = malabsorption

Question 24

pancreatic secretions: cephalic phase

Answer 24

food stimulus = increased vagal nerve activity via Ach

increased vagal nerve activity = increased activity from acinar cells and ductal cells

increased secretion of enzymes and HCO3 secretion

Question 25

pancreatic secretions: gastric phase

Answer 25

food in stomach =

gastric distension = increased vagal response = Ach receptors = enzyme release (acinar cells)

gastric secretion = increased gastrin = CCKb receptor activation = enzyme release (acinar cells)

protein in food = increased CCK = activation of CCK receptors = enzyme secretion (acinar cells)

Question 26

distal colon and NaCl absorption

Answer 26

when the body has low Na levels

aldosterone stimulates the ENaC pump to promote Na retention

aldosterone also enhances K excretion
K moves passively (normal)

Question 27

secretory diarrhea

Answer 27

increased endogenous secretions of fluid and electrolytes from GIT

usually due to bacterial toxins, tumors, or hormones

Question 28

Diarrhea and K

Answer 28

increases rate of fluid loss into the GIT leads to a loss of K

can lead to hypokalemia