Heme Sythesis & Degradation Flashcards
Hemoglobin gives RBCs the ability to transport ________ throughout the body
Oxygen
Hemoglobin is composed of ____ globular sub-units each bound to an ______ containing _______
4
Iron
Heme
Heme has a heterocyclic __________ ring with ______ present in the center
Porphyrin
Iron
Each porphyrin ring contains ____ 5-membered rings. Each ring contains ______ connected by single ____________.
Each porphyrin contains FOUR 5-membered rings. Each ring contains NITROGEN and is connected by single CARBON BRIDGES.
Iron is present in hemoglobin is __________ state
Ferrous
Heme is present in __________, __________, &. ___________.
Hemoglobin, myoglobin, and cytochromes
Heme synthesis occurs primarily in what parts of the body?
Liver
Erythropoietin cells of bone marrow
Where does each phase of the biosynthesis of heme take place?
Phase I : mitochondria
Phase II : cytoplasm
Phase III: mitochondria
What are the starting ingredients of heme synthesis?
What inhibits the first step of the process?
Succinyl CoA and Glycine
Heme inhibits
In the synthesis of heme, what crossed the cytoplasmic barrier (from mitochondria to cytoplasm)?
ALA
In the synthesis of heme, what crosses the mitochondrial barrier (from cytoplasm to mitochondria)?
Copro-porphyrin open III
A defect in one or more stages of heme synthesis will lead to________
Porphyria
Which porphyria is autosomal recessive? A) Variegated porphyria B) Acute intermittent porphyria C) Congenital erythropoietic porphyria D) Porphyria cutanea tarda
C) Congenital erythropoietic porphyria
ALA Synthase is used in the first step of heme synthesis. In order to function, it needs ________ which has a cofactor of __________.
PLP (pyridoxal phosphate)
Vitamin B6
A deficiency in ALA-synthase or Vitamin B6 will cause ______
Anemia
In the first step of heme synthesis, Succinyl CoA is __________ producing a byproduct of CO2.
Decaroxylated
TRUE or FALSE: Porphyrias are INHERITED metabolic disorders.
TRUE
When you see neurological symptoms in a porphyria patient, you would expect what type of disease?
Acute hepatic
When you see skin issues and photosensitivity in a porphyria patient, you would expect what type of disorder?
Erythropoietic
Acute intermittent porphyria
Deficient enzyme: ?
Type of porphyria: ?
Autosomal recessive or dominant?
What is produced in excess?
Symptoms: ?
Porphobilinogen deaminase
Hepatic
Dominant
ALA and PBG
Neurological disfunction and abdominal pain
Congenital erythropoietic porphyria
Deficient enzyme: ?
Type of porphyria: ?
Autosomal recessive or dominant?
What is produced in excess?
Symptoms: ?
Uroporphyrinogen III (co)synthase
Erythropoietic
Recessive
Uroporphyrinogen I and its red-colored, air oxidation product uroporphyrin
Photosensitivity, red color in urine and teeth; hemolytic anemia
Porphyria Cutanea Tarda
Deficient enzyme: ?
Type of porphyria: ?
Autosomal recessive or dominant?
What is produced in excess?
Symptoms: ?
Uroporphyrinogen Decarboxylase
Hepatoerythropoietic
Dominant
Uroporphyrinogen III which converts to uroporphyrinogen I
Photosensitivity resulting in vesicles and bullpen on skin, red-wine colored urine
*Most common porphyria in the United States
Variegate porphyria
Deficient enzyme: ?
Type of porphyria: ?
Autosomal recessive or dominant?
Symptoms: ?
Protoporphyrinogen IX Oxidase
Hepatic
Dominant
Photosensitivity & Neurologic symtoms and developmental delay in children
*King George III
RBC undergo breakdown every ____ days and this is handled by the ______-endothelial system, which degrades ________
Globin is broken down into ______ and ______ which is removed for degradation.
120
Reticulo -endothelial
Hemoglobin
Amino acids & heme
Heme is what color in the body?
What enzyme converts heme to biliverdin?
Heme = purple
Heme oxygenase
What color is biliverden?
What enzyme converts biliverdin to bilirubin?
Biliverdin = green
Bilirubin reductase
What color is bilirubin in the body?
What does bilirubin associate with in the bloodstream?
Bilirubin = Red-orange
Albumin
In the liver, bilirubin requires what to go from “indirect” to “direct” - Bilirubin-monoglucuronide?
UDP-glucoronyl transferase
*rate-limiting rxn
In the liver, Bilirubin-monoglucuronide “indirect” requires what to go to Bilirubin-diglucuronide “direct”?
UDP-glucoronyltransferase
(Yes it’s the same enzyme as the previous reaction)
*rate-limiting rxn
In the small intestine, bilirubin-diglucoronide goes to ________ which goes to _________.
Bilirubin
Urobilinogen
Urobilinogen can either stay in the ________ and go to ________ with the help of microbial enzymes to be excreted as ________ OR it can go to the ______ where it will be converted to __________ to be excreted as _________.
Small intestine
Stercobilin
Feces
Kidney
Urobilin
Urine
Which of the following is yellow and which is colorless?
Urobilinogen
Urobilin
Urobilinogen = colorless
Urobilin = yellow
Crigler-Najjar Syndrome and Gilbert syndrome are associated with a deficiency in what enzyme?
Glucuronyl transferase
<10% residual activity (CN)
25% residual activity (G)
The oxidation of heme liberates one of the ____________as ________,converts the________iron into ________iron and produces the green pigment __________.
Carbon bridges CO (carbon monoxide) Ferrous (Fe2+) Ferric (Fe3+) Biliverdin
Reduction of biliverdin produces the red-orange bilirubin that is conjugated in the _________, collected in _______ and secreted into the _____________,where it undergoes _____________ to urobilinogen
Liver
Bile
Small intestine
Microbial reduction
T or F: The iron in the porphyrin ring of heme is in the ferrous form.
True, the iron in heme is 2+ which is the ferrous form
The ferric form of iron is Fe3+
In heme degradation, the enzyme ___________ removes the bridge between pyrole rings of heme, releasing ________. Iron is oxidized from __________ to __________.
The enzyme used above is induced 100x by ______, _________ and __________.
Heme oxygenase
CO
Ferrous to ferric
Heme, metal ions, phenylhydrazine (a drug)
The enzyme responsible for degrading heme to biliverdin is _________. The enzyme used to take biliverdin to bilirubin is __________ and _______ is also needed.
Heme oxygenase
Biliverdin reductase
NADPH
Bilirubin is released into the bloodstream but because free/unconjugated/indirect bilirubin is _________, it is bound to _________.
Insoluble
Albumin
A protein carrier is needed for _________ uptake of bilirubin.
Bilirubin is conjugated with _________ to make it ________. This form is called _______ bilirubin.
Hepatic
Glucoronic acid
Soluble
Direct
What is the rate limiting step in the removal of bilirubin from blood?
If babies do not have sufficient amounts of this enzyme, they will get?
UDP glucoronyl transferase
Jaundice
Pre-hepatic jaundice indicates ________ production of ______________ bilirubin
An increased
Unconjugated
Excess hemolysis, internal hemorrhage, neonatal jaundice due to problems with incompatibility of maternal-fetal blood groups is associated with pre, intra or post hepatic jaundice?
Pre-hepatic jaundice
*With pre-hepatic jaundice, you would expect to see ______ blood levels of _______ or ________ bilirubin,
Normal levels of _______ BR
________ levels of ALT and AST.
And ______ would be present in urine but not ________.
Elevated
Unconjugated or indirect
Direct
Normal
Urobilinogen
Direct BR
Intra-hepatic jaundice is characterized by ___________ hepatic uptake, conjugation or secretions of conjugated BR.
Examples include?
Impaired (hepatic uptake)
Liver cirrhosis
Viral hepatitis
Criggler-Najjar syndrome
Gilbert syndrome
*Often due to drug abuse
With intra-hepatic jaundice, you would expect to see ______ in _________ and _________ bilirubin.
__________ in ALT and AST
__________ levels of urobilinogen in urine
And __________ detected in urine as well
Variable increases
Unconjugated and conjugated
Increases
Normal
Conjugated BR
Post-hepatic jaundice involves problems with ___________ and is also called ________ which means decrease _______ flow
Bilirubin excretion
Cholestasis
Bile
Post-hepatic involves obstruction to _______ drainage in _______ or _______ and can present as…..
Biliary
Liver or bile ducts
Gall stones, cholangiocarcinoma, infiltrative liver disease, lesions (tumor, abscess or granulomatous disease)
With post-hepatic, you would expect to see ________ blood levels of conjugated BR
_____ levels of ALT and AST
_______ ALP and bile salts
________ is present in urine, making it _______
And there is no _______ in feces so they are ______
Elevated
Normal
Elevated
Conjugated BR
Dark
Stercobolin
Pale
Autoimmune, abnormal hemoglobin are clinical examples of _________ jaundice
Prehepatic
Hepatitis A, B, C, acetaminophen or alcohol induced, Gilbert’s syndrome, Crigler-Najjar syndrome, DUbin-Johnson Syndrome, Rotor’s syndrome, Wilson’s disease, neonatal are all clinical examples of __________ jaundice
Intrahepatic
Drug use, primary biliary cirrhosis, cholangitis, gall stones, pancreatic tumor, cholangiocarcinoma are all clinical examples of __________ jaundice
Post-hepatic
Gilbert’s syndrome, Crigler-Najjar syndrome, Dublin-Johnson syndrome, Rotor’s Syndrome are all clinical examples of intrahepatic jaundice due to ___________in bilirubin __________
genetic errors
Metabolism
Neonatal jaundice is also called _________ jaundice and is due to elevated __________ bilirubin.
Major contributing factors include:
- the breakdown of _______ as it is replaced with adult hemoglobin
- immature _______ metabolic pathways, unable to ________ and ______bilirubin
- deficiency of _______ enzyme
Physiological
Unconjugated
Fetal hemoglobin
Hepatic
Conjugate & excrete
UDP-GT
___________ is a common treatment for neonatal jaundice. The exposure to ________ turns bilirubin into a ________ form, which makes it easier to excrete.
Phototherapy
Light
Soluble
In ___________ syndrome type I, patients are born without _________ , in type II, patients are born with a mutated form of _______ resulting in _____ activity.
Criggler-Najjar
UDP-GT
UDP-GT
10%
*Criggler-Najjar Syndrome causes BR to ___________ in the _________ of ________,which causes___________and _________.
Therapy includes: ??
Accumulate in the brain of babies
Encephalopathy & brain damage
Blood transfusions, phototherapy, heme oxygenase inhibitors, oral calcium phosphate and carbonate,liver transplantation (before brain damage occurs and before phototherapy becomes ineffective)
Gilbert Syndrome results in __________ activity of __________ (enzyme) ___%
Serum BR may increase with _____, ______or ______
Gilbert syndrome affects ____ of the population
Reduced UDP-GT
25%
Fasting, stress or alcohol consumption
2-10%, relatively common
Hepatitis means ________ of the _________
Causes include viral infections such as ______, ______& ______, as well as _________ and __________
We see ______ levels of unconjugated and conjugated bilirubin in blood
Causes a _____ discoloration in the _____ and _______.
Urine is _______
Inflammation
Liver
Hep A, B & C
Alcoholic cirrhosis
Liver cancer
Elevated
Yellow
Skin and sclera of the eyes
Tea-colored (urine)
Bruises change colors based on the breakdown of ________ from …
Heme which is ______
To ________ which is _______
To ________ which is _______
To _________ which is _______
Hemoglobin
Red/purple
Biliverdin=green
Bilirubin = orange/red
Hemosiderin = brown
