Uth Biochemistry Block Iii Lecture 3

Front 1

Creatine is synthesized from what two amino acids?

Back 1

Glycine and Arginine.

Front 2

Explain the biosynthesis of creatine.

Back 2

Glycine and arginine are coupled to produce guanidinoacetate in the kidney. This travels through the circulation to the liver where SAM methylates to form creatine (SAM goes to SAH).

Front 3

How is creatine phosphate derived and for what purpose?

Back 3

Creatine phosphate is made in the muscle and brain by the edition of creatine and a phosphate from ATP. Creatine phosphokinase (CPK) is utilized. Creatine phosphate is a high energy reservoire for energy.

Front 4

Creatine phosphate spontaneously breaks down to form ____.

Back 4

Creatinine. This is the cyclized product and is excreted in the urine.

Front 5

What is structure of heme?

Back 5

Hydrophobic porphyrin ring containing iron. Requires 8 succinyl CoA and 8 glycine molecules.

Front 6

Heme is synthesized from succinyl CoA and gylcine. This process involves 8 steps. What is the rate limiting step and how is it regulated?

Back 6

ALA Synthase (PLP) converts glycine and Succinyl-CoA into delta-ALA. This is the first committed step and is located in the mitochondria. Heme can both downregulate its transcription as well as allosterically inhibit the protein.

Front 7

What inhibits steps in heme production?

Back 7

Lead inhibits step 2: delta-ALA to PBG, as well as Protoporphyrin IX to Heme. This step incorporates Fe into the ring. Enzyme = ferrochelatase (heme synthase).

Front 8

What is the definition of porphyrias?

Back 8

Porphyrias are defined as deficiencies in heme biosynthetic pathway. This group of diseases has numerous types. All result in decreased synthesis of heme, which causes decreased inhibition of ALA synthase which leads to accumulation of intermediates prior to site of deficiency often causing toxic effects on NS and skin damage. Often AD.

Front 9

Acute Intermittent Porphyria

Back 9

1/2 normal activity of porphobilinogen deaminase. AD. Increase in PBG cuases peripheral neuropathy and CNS problems; anxiety, disorientation, hallucination, paranoia, and seizures. Abdominal pain can be severe.

Front 10

Congential Erythropoietic Porphyria

Back 10

Deficiency of uropophyringoen III cosynthase. AR. Increased urinary porphyrin excretion. Buildup of non physiological porphyrins in bone marrow and skin result in damage to RBC and cutaneous photosensitivity.

Front 11

Variegate Porphyria

Back 11

High in white South Africans. Acute attacks; cutaneous photosensitivity.

Front 12

All porphyrias can cause accumulation of planar hydrophobic molecules with ___ colored urine and lesions as well as excessive hair growth, "wolf-man" and "dracula".

Back 12

purple

Front 13

Degradation of Heme. Phagocytosis in cells cleave globin and iron s restored to the body's iron stores. Heme is degraded to ____.

Back 13

Bilirubin which is transported to the liver complexed with serum albumin.

Front 14

Bilirubin is conjugated to form ____, which is more ____ and is excreted into the bile.

Back 14

bilirubin diglucoronide
soluble

Front 15

In the intestine ____ deconjugate bilirubin diglucoronide to form ____.

Back 15

bacteria
urobilinogen

Front 16

What are the fates of urobilinogen?

Back 16

Absorbed into the blood and excreted in the urine or oxidized to stercobilin which is excreted in feces.

Front 17

Jaundice is indicative of?

Back 17

Hyperbilirubinemia either by excessive heme degradation or inadequate clearance of bilirubin. Leads to yellow skin and sclera. Indicative of:
hemolytic crisis
neonatal jaundice
Crigler Najjar
liver disease
structural blockage of hepatic or common bile ducts

Front 18

Bilirubin in serum is measured in two forms, name them.

Back 18

Direct- conjugated; non-protein bound
Indirect- non-conjugated; protein bound

Front 19

NO is mainly used for ____.

Back 19

Vasodilation

Front 20

NO is synthesized by ____.

Back 20

Arginine, NADPH, and O2 to form citrulline and NO. Via NO synthase.

Front 21

NO is produced in response to a stimulator molecule or via ____.

Back 21

production of NO from nerve impulses in neurons.

Front 22

NO acts on ____.

Back 22

Guanylate cyclase to convert GTP into cGMP which causes vessel relaxation = vasodilation.

Front 23

cGMP is degraded to GMP by ____.

Back 23

PDE = cGMP phosphodiesterases; Viagra inhibits this enzyme for prolonged elevations of cGMP.

Front 24

Decarboxylation of Glutamate (PLP) forms ____.

Back 24

GABA, a neurotransmitter in inhibitor pathways.

Front 25

List the sequential products of tryptophan.

Back 25

Tryptophan, 5-Hydroxytryptophan, Serotonin, N-Acetylserotonin, and Melatonin (needed to regulate circadian rhythms).

Front 26

In neurons Tyrosine metabolites are ____.

Back 26

DOPA, Dopamine, and NE.

Front 27

In the adrenal medulla the Tyrosine metabolites are ____.

Back 27

DOPA, Dopamine, NE, and E.

Front 28

In melanocytes Tyrosine forms ____.

Back 28

DOPA via a Cu dependent tyrosine hydroxylase (different from neurons), which is used to form melanins.

Front 29

Polyamines are highly cationic molecules that are essential for ____.

Back 29

cell growth and differentiation. They interact with nucleic acids, proteins and membranes.

Front 30

Ornithine decarboxylase is present in what type of cell activity?

Back 30

Rapidly dividing cells.

Front 31

The spontaneous breakdown product of creatine phosphate is creatinine. What is creatinine proportional to?

Back 31

Muscle mass.

Front 32

Creatinine can be used as a ____ for urine tests because it's secreted regularly.

Back 32

Normalizer.

Front 33

Most porphyrias are AD in nature, why is that?

Back 33

This is due to heme not being synthesized in concentrations that can downregulate the ALA synthase (both at transcription and protein levels), so therefore more products are made and these buildup at whatever level they occur. This downregulation by heme is clearly essential for normal functioning.

Front 34

CPK is used to determine myocardial infarctions. Why is that?

Back 34

CPK should not normally be found in the bloodstream and is released due to cardiac cell lysis. Note: it is the CPK-cardiac isoform quantified.

Front 35

What is the color of Heme, Biliverdin, and Bilirubin?

Back 35

Heme- red
Biliverdin- green
Bilirubin- reddish, orange and in low quantities it's yellow
*stages of a bruise

Front 36

Bilirubin travels in the bloodstream bound to serum. In the liver this enzyme conjugates or non-conjugates the bilirubin in order to ____?

Back 36

Enzyme = Bilirubin UDP-glucuronosyl-transferase
conjugates = Bilirubin diglucuronide
Increases solubility

Front 37

Clinical Analysis:
Increased Direct levels, but normal Indirect.

Back 37

Could mean bile duct obstruction; the bilirubin conjugated is getting out of the liver, but stays in the bloodstream and cannot enter the gallbladder.

Front 38

Clinical Analysis:
Increased Indirect levels, but low Direct.

Back 38

Most likely a transferase problem. This is an issue with babies at birth since Bilirubin UDP-glucuronosyl-transferase is not made until late development. UV light can be used as a treatment to help mobilize/break down bilirubin.

Front 39

Clinical Analysis:
Increased both Direct and Indirect levels.

Back 39

Breaking down LOTS of heme. Possible hypebilirubinemia.