Heme Synthesis

Front 1

--Indicate whether or not the oxidation state of heme iron is important. Give some
examples to support your answer.

Back 1

--The oxidation state of the heme iron is super important. It has to be in the +2 state or the heme proteins wont function correctly.
--Glutathione reduces oxidizing agents before they can oxidize hemes +2 iron.
--Two glutathione-SH groups are oxidized to glutathione-S-S-glutathione in this process

Front 2

--Indicate the structural feature of glutathione which makes it useful for preventing unwanted oxidation.

Back 2

--Glutathione reduces oxidizing agents before they can oxidize hemes +2 iron.

--Two glutathione-SH groups are oxidized to glutathione-S-S-glutathione in this process

--So it is the cystine in it that is the key structural feature.

Front 3

--Name the nucleotide which is oxidized to reduce oxidized glutathione in relation to preventing hemoglobin heme oxidation

Back 3

NADPH is oxidized to NADP+ in the process.

Front 4

Name the pathway which reduced the nucleotide oxidized NADP+

Back 4

NADP+ is reduced via the pentose phosphate pathway

Front 5

What is/are the process to reduce Fe3+ tp Fe2+

Back 5

The methemoglobin reductase reaction:

1) Methemoglobin heme iron +3 is reduced to +2.

2) NADH is oxidized to NAD+ in this process.

3) Glycolysis re-reduces the resulting NAD+ to NADH.

NOTE: This process can correct only
minor amounts of heme iron oxidation

Front 6

Is heme synthesis an ongoing process?

Back 6

Yes.

The porphyrin ring of heme is not recycled when hemoglobin and other heme proteins are catabolized.

Front 7

What does lead inhibit in heme synthesis?

Back 7

ferrochelatase.

Front 8

What are the starting materials needed for heme synthesis?

Back 8

--Succinyl CoA from the TCA cycle

--Glycine

--Fe+2

Front 9

Where is heme synthesized?

Back 9

Reticulocytes, hepatocytes, other cells synthesizing heme iron proteins

Front 10

Describe Aminolevulinic acid (ALA) synthase in the heme synthesis pathway.

Back 10

First enzyme in pathway

--requires a B6 cofactor.

--is feed back inhibited by heme.

--Heme also regulates expression of the genes for alpha and beta globin chains of hemoglobin.

Front 11

Can lead cause porphyrias

Back 11

yeppers

Front 12

Fe Metabolism
What does ferritin do?

Back 12

assists in gut iron absorption
and in
shorter term iron storage.

Front 13

Fe Metabolism
What does Transferritn do?

Back 13

–--assists in gut iron absorption
--and in shorter term iron storage

Front 14

Fe Metabolism
What does hemosiderin do?

Back 14

involved in longer term iron storage.

Front 15

Where does most Fe storage occur?

Back 15

Da Liver!

Front 16

Is Fe loss common?

Back 16

No, except via blood loss.

Front 17

Bilibrubin is produced by who and how does it get around the blood?

Back 17

produced in RE cells including spleen.

transported in the bloodstream bound to albumin.

Front 18

What is Bilirubin diglucuronide

Back 18

--is produced by hepatic conjugation of bilirubin.

--Glucuronyl transferase catalyzes this reaction.

--Activated UDP-substrate is used in this reaction.

--is excreted via the gall bladder.

--Bacterial action converts bilirubin diglucuronide to urobilinogen and stercobilin in the intestine.

Front 19

Is conjugated bilirubin bound to albumin?

Back 19

Negator fagator and hence it can be measured directly.

Front 20

Bilirubin equation.

Back 20

Total bilirubin – direct bilirubin = indirect bilirubin

Front 21

What does the presence of direct conjugated bilirubin in serum indicate?

Back 21

The presence of conjugated, direct bilirubin in the serum is abnormal and indicates a hepatic post-conjugation or post hepatic pathology in the heme catabolism pathway.

Front 22

Is the presnce of unconjugated indirect bilirubin in serum indicative of pathology?

What is pathological?

Back 22

--The presence of some indirect, unconjugated serum bilirubin is normal.
--Elevated levels of this form of bilirubin are indicative of a pre-hepatic or hepatic pre-conjugation pathology in the heme catabolism pathway.

Front 23

From module 2

Some hepatic enzymes are not needed in utero and are not fully expressed at birth, especially in the case of premature infants. Explain how this fact could result in the jaundice you observed.

Back 23

Less glucuronyl transferase is expressed in newborns so that less bilirubin conjugation can occur. As a result unconjugated bilirubin levels rise in the serum.

Front 24

From module 2

1-3. Bili-lights are the first line of therapy for neonatal jaundice. In a few words, what do these lights do?

Back 24

The light energy breaks the unconjugated bilirubin into smaller molecules which the kidneys can excrete more readily thus decreasing bilirubin levels.

Front 25

From module 2

1-4. If serum bilirubin reaches a critical level in this infant, transfusion will be necessary. In a few words, why is the presence of elevated bilirubin more problematic in the neonate than in the adult?

Back 25

The blood-brain barrier is less effective in infants; at high enough levels unconjugated bilirubin may enter the brain causing permanent damage.

Front 26

Why can elevated billirubin levels or jaundice result in tea colored urine?

Back 26

The kidneys remove some of the direct bilirubin and the molecules it breaks down into spontaneously. These molecules are yellow/red/brown entities.

Front 27

What does Coumarin warfarin do?

Back 27

Coumarins (Warfarin, Coumadin) are used in medical conditions requiring oral anticoagulation and are also found in rodent poisons. These molecules decrease coagulation by inhibiting vitamin K epoxide reductase which is important for returning vitamin K to its reduced form after it has participated in the carboxylation of coagulation proteins.

Front 28

What coag factor has the shortest half life?

Back 28

Factor VII has the shortest half life of all coagulation factors and is therefore most sensitive to vitamin K levels.

Front 29

What is • Disseminated intravascular coagulation(DIC)

Back 29

DIC is a loss of control over coagulation caused by abnormally sustained generation of thrombin leading to bleeding and thrombosis. It is most frequently associated with sepsis and complications of pregnancy.

Front 30

What is D-Dimer?

Back 30

D-dimer is a degradation product of fibrin generated by fibrinolysis. Normal plasma does not have detectable amounts of D-dimer. The presence of this product is confirmatory for DIC and other thrombotic problems

Front 31

What is a mixing study?

Back 31

: Mixing studies are done to distinguish between a coagulation factor deficiency and a coagulation factor inhibitor. The test procedure involves mixing equal volumes of patient plasma and normal pooled plasma, then measuring the PT of the mixture. Full correction of the PT into the reference range suggests a deficiency of a coagulation factor within the extrinsic coagulation pathway, such as factor VII. Inherited factor VII deficiency is a very rare condition; it can be confirmed by demonstrating a low factor VII level in the patient and a low factor VII level in one or both parents.
Incomplete correction of the PT after mixing with normal plasma suggests the presence of a factor VII inhibitor (autoantibody), an exceedingly rare condition. Performing a factor VII assay and a Bethesda assay (which can detect anti-factor VII antibodies) will confirm this diagnosis.

Front 32

What is a liver function test?

Back 32

These may include indicators of hepatocellular damage such as aspartate aminotransferase and alanine aminotransferase (these proteins are small and leak out of damaged liver cells), indicators of biliary function, and indicators of synthetic function such as albumin which is the most abundant protein synthesized by the liver.

Front 33

Describe acquired inhibitors antibodies in nonhemophiliacs?

Back 33

Acquired inhibitors/autoantibodies against clotting factors in nonhemophiliacs is extremely rare. Patients who develop such acquired inhibitors may present with catastrophic bleeding episodes despite having no prior history of a bleeding disorder.

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