Chapter 17: Amino Acids (continued) Flashcards
Draw out a diagram for folate metabolism.
Vitamin B12 is reduced and activated in the body to what 2 forms?
- adenosylcobalamin (used by methylmalonyl-CoA mutase)
- methylcobalamin (formed from N5-methyl-THF in the N- methyl THF homocysteine methyltransferase reaction)
The full name for D. latum?
Diphyllobothrium latum
What is D. latum?
a parasite found in raw fish (excess B12 is stored in the body, so deficiencies develop slowly)
What would happen to symptoms of cobalamin deficiency if you gave folate?
It would correct the megaloblastic anemia but does not halt the neuropathy
How does deficiency of Vit. B12 affect the CNS specifically?
causes demyelination of the posterior columns and lateral corticospinal tracts in the spinal cord
What are some symptoms of folate deficiency?
megaloblastic anemia
- macrocytic anemia
- MCV > 100 femtoliters (fL)
- PMN nucleus more than 5 lobes
Homocysteinemia with risk for cardiovascular disease
- NTD
What are some causes of folate deficiency?
- pregnancy (NTD)
- alcoholism
- severe malnutrition
- gastric or terminal ileum resection
What are some of the symptoms of Vit B12 deficiency?
macrocytic anemia
MCV > 100 femtoliters (fL)
PMN nucleus more than 5 lobes
Homocysteinemia with risk for CVS disease
methylmalonic aciduria
progressive peripheral neuropathy
Compare the time it takes for folate deficiency and B12 deficiency to be evident?
3-4 months folate while B12 deficiency normally takes years to develop
What are some specialized products that tyrosine can make?
- thyroid hormones T3 and T4
- melanin
- catecholamines
What are some specialized products in the body that tryptophan can make?
serotonin and NAD NADP (niacin)
What are some specialized products that arginine can make?
Nitric oxide (NO)
What are some specialized products that glutamate can make?
y-aminobutyric acid (GABA)
What are some specialized products histidine can make?
histamine
Draw out the pathway for catecholamine synthesis.
Name some products in the body in which heme proteins are included?
hemoglobin
myoglobin
all the cytochromes (ETC)
cytochrome P-450, cytochrome b5
the enzymes catalase, peroxidase, and the soluble guanylate cyclase stimulated by NO
What is the rate-limiting enzyme for heme synthesis?
δ-aminolevulinate synthase (ALA)
Are compounds with an “ogen” at the end of their name colorless or colorful?
Compounds such as urobilinogen, are colorless
Are compounds with the suffix such as urobilin colorful or colorless?
colorful
How does a compound like urobilinogen change to urobilin and get color?
In the presence of O2, they spontaneously oxidized
Draw out the pathway for heme synthesis.
What are some symptoms of acute intermittent porphyria? What would increase on labs?
- episodic, variable expression
- anxiety, confusion, paranoia
- acute abdominal pain
- port-wine urine in some patients
- paralysis
- motor sensory or autonomic neuropathy
- weakness
- excretion of ALA (d-aminolevulinic) and PBG (porphobilinogen) during episodes
What is a drug you can never give individuals with acute intermittent porphyria?
never give barbituates
What are some symptoms of porphyria cutanea tarda?
- most common porphyria
- photosensitivity
- inflammation, blistering, shearing of skin in areas exposed to sunlight
- hyperpigmentation
- exacerbated by alcohol
- red-brown to deep-red urine (tea colored urine)
What are other names for acute intermittent porphyria?
- porphobilinogen deaminase deficiency
- hydroxymethylbilane synthase deficiency
Inheritance pattern of acute intermittent porphyria?
AD
When, in a humans life, will acute intermittent porphyria typically appear?
late onset
T/F. Some of the individuals suffering with acute intermittent porphyria are incorrectly diagnosed and placed in psychiatric institutions.
True
Do individuals with acute intermittent porphyria have photosensitivity?
no
Porphyria cutanea tarda results because of a deficiency of what enzyme?
deficiency of uroporphyrinogen decarboxylase
What are substances that can exacerbate porphyria cutanea tarda?
hepatotoxic substances, such as excessive alcohol or iron deposits
What are the skin lesions in porphyria cutanea tarda caused by?
related to high circulating levels of porphyrins
What drug is associated with B6 deficiency?
deficiency of pyridoxine is associated with isoniazid therapy for tuberculosis
What is the enzyme that introduces the iron into the heme ring?
ferrochelatase introduces Fe2+ into the heme ring
Give the MOA by which barbiturates can exacerbate prophyrias?
barbiturates are hydroxylated by microsomal cytochrome P-450 system in the liver to facilitate their efficient elimination from the body.
Administration of the barbiturates results in stimulation of cytochrome P-450 synthesis, which in turn reduces heme levels.
Reduction in heme lessens the repression of ALA synthase, causing more porphyrin precursor synthesis.
The indirect production of more precursors by barbiturates exacerbates the disease
What are some enzymes that that lead inactivates?
many including ALA dehydratase and ferrochelatase (heme synthase)
Another name for ferrochelatase.
heme synthase
What are some symptoms of lead poisoning?
- coarse basophilic stippling of erythrocytes
- headache, nausea, memory loss
- abdominal pain, diarrhea (lead colic)
- lead lines in gums
- lead deposits in abdomen and epiphysis of bone seen on radiography
- neuropathy (claw hand, wrist-drop)
- increased urinary ALA
- increased free erythrocyte protoporphyrin
MOA of your body creating zinc-protoporphyrin?
failure of ferrochelatase to insert Fe2+ into protoporphyrin IX to form heme, such as in lead poisoning or iron deficiency anemia, results in the nonenyzymatic insertion of Zn2+ to form zinc-protoporphyrin
What is an important property of zinc protoporphyrin?
This complex is extremely fluorescent and easily detected
What is the inheritance pattern of hemochromatosis?
AR
How is hemochromatosis caused?
when there is a daily intestinal absorption of 2-3 mg of iron compared with the normal 1 mg because of a hepcidin mutation over several years then this condition occurs
Ferritin binds what type of iron?
Fe3+ ferric iron
Fe2+ is what type of iron?
ferrous iron
Which type of anemia can cause coarse basophilic stippling in the erythrocyte?
lead poisoning
What type of anemia is caused by pyridoxine deficiency? (macrocytic, normocytic, or microcytic?)
mirocytic
Which type of anemia is caused by iron deficiency anemia?(macrocytic, normocytic, or microcytic?)
microcytic
Which type of anemia is caused by lead poisoning? (macrocytic, normocytic, or microcytic?)
microcytic
Which type of anemia will cause ringed sideroblasts in bone marrow to be seen?
lead poisoning
Describe protoporphyrin levels in Vit. B6 deficiency, iron deficiency, and lead poisoning.
B6 Protoporphyrin: decreased
Iron def: Protoporphyrin: increased
Lead poisoning Protoporphyrin: increased
Describe d-ALA levels in vitamin B6 deficiency, iron def., and lead poisoning.
B6 def ferritin: decreased
Iron deficiency: normal
lead poisoning: increased
Describe serum iron in B6 def, iron def, and lead poisoning.
B6 serum iron: increased
Iron deficiency serum iron: decreased
Lead poisoning serum iron: increased
What are some ways in which one can get lead poisoning?
lead paint, pottery glaze, batteries
How would you diagnose if one has lead poisoning?
by measuring blood lead levels
What is another name for ferroxidase?
aka ceruloplasmin
What is ceruloplasmin?
a Cu2+ protein enzyme that oxidizes Fe2+ to Fe3+ for transport and storage
How do we lose ferritin from the body?
by bleeding and shedding epithelial cells of the mucosa and skin
What binds excess Fe3+ to prevent escape of free Fe3+ into the blood?
hemosiderin
Be able to draw out a diagram for iron metabolism.
refer to diagram
How do hepatocytes make bilirubin water soluble?
they conjugate it to glucuronic acid
What converts conjugated biilrubin to urobilinogen?
intestinal bacteria
Bile duct obstruction can lead to what colored stools?
clay colored
What causes the red-brown color of feces?
urobilinogen being further converted to bile pigments (stercobilin) and excreted in the feces
AT , very high levels, how can bilirubin lead to kernicterus?
bilirubin may cross the blood brain barrier and precipitate in the basal ganglia, causing irreversible brain damage
Be able to create a diagram on heme catabolism and bilirubin.
Refer to diagram.
Another name for UCB?
unconjugated bilirubin (indirect bilirubin)
Another name for conjugated bilirubin?
direct bilirubin
What are some examples of hemolytic crisis developing and causing jaundice and kernicterus.
episode of hemoylysis in G6PDH deficiency
Sickle cell crisis
Rh disease of the newborn
Crigler Najjar syndrome Type I pathology?
Absent UDP - glucuronyltransferase
Crigler Najjar syndrome Type II pathology?
Deficiency of UDP-glucruonyltransferase enzyme but not absence like Type I
Gilbert syndrome pathology
Deficiency of UDP - glucuronyltransferase but to a much lesser extent than Crigler Najjar Type II. Usually jaundice is brought about by triggers (stress, alcohol, fasting/starvation)
How does phyisologic jaundice of the newborn occur?
becuase the enzyme glucuronyl transferase may not be fully induced
Viral hepatitis or cirrhosis produces an increase in which type of bilirubin? (direct or indirect)
both direct and indirect
Which is higher in alcoholic liver disease AST or ALT?
AST increases more than ALT
Which is higher in viral hep ALT or AST?
ALT increase more than AST
What is the color of feces if conjugated bilirubin increases in the blood?
feces are light colored or clay colored. Because its a increased because of bile duct obstruction.
