Amino Acid Degradation and Synthesis

Question 1

What are termed Glucogenic or Glycogenic amino acids?

Answer 1

Amino acids whose catabolism yields pyruvate or one of the intermediates of the citric acid cycle are termed glucogenic or glycogenic. These intermediates are substrates for gluconeogenesis and, therefore can give rise to the net formation of glucose or glycogen in the liver and glycogen in the muscle.

Question 2

What are ketogenic amino acids? What are the amino acids found in protein, that are exclusively ketogenic?

Answer 2

Amino acids whose catabolism yields either acetoacetate or one of its precursors (Acetyl coA or acetoacetyl coA) . Leucine and Lysine are the only exclusively ketogenic amino acids found in proteins.

Question 3

Folic acid helps with the degradation of which amino acid? What happens when there is a deficiency?

Answer 3

Individuals deficient in folic acid excrete increased amounts of FIGLu in the urine, particularly after ingestion of a large dose of histidine. The FIGLu excretion test has been used in diagnosing a deficiency of folic acid.

Question 4

What is the amino acid that form OAA?

Answer 4

Aspartate

Question 5

What are the A.A. that can form alpha-ketoglutarate?

Answer 5

Glutamine, Proline, Arginine, Histidine “Go Practice Histo Again”

Question 6

What amino acid form OAA?

Answer 6

Aspartate. Asparagine is hydrolyzed by asparaginase, liberating ammonia and aspartate.

Question 7

What amino acids can form pyruvate?

Answer 7

Alanine, Serine, Glyicne, Cystine, Threonine

Question 8

Deficiencies in the enzymes of phenyalanine and tyrosine metabolism lead to which diseases?

Answer 8

Phenylketonuria, and Alkaptonuria. Also albinism.

Question 9

Methionine is an amino acid that can form from which TCA cycle derivative?

Answer 9

Succinyl CoA

Question 10

After hydrolysis of SAM, Homocysteine can undergo two pathways, remethylation or transsulfication.

Explain the remethylated pathway

What vitamin do we need?

Answer 10

Homocysteine accepts a methyl group from N5-methltetrahydrofolate (N5-methul-THF) in a rx requiring methylcobalamin, a coenzyme derived from B12. The methyl group is transferred from the B12 derivative to homocysteine, and cobalamin is recharged from N5-methul-THF.

Question 11

After hydrolysis of SAM, Homocysteine can undergo two pathways, remethylation or transsulfication.

Explain the transsulfication pathway

What vitamin is needed?

Answer 11

Homocysteine condenses with serine, forming cystathionine, which is hydrolyzed to alpha-ketobutyrate and cysteine.

This vitamin B6-requiring sequence has the net effect of converting serine to cysteine and homocysteine to alpha-ketobutyrate, which is oxidativly decarbaoxylated to form propionyl CoA.

Question 12

what will happen if we have increase homocysteine levels?

What can be a treatment for this?

Rare deficiencies of what enzyme will cause increase levels of homocysteine?

Answer 12

Eleveations in plasma homocysteine levels promote oxidative damamge, inflammation, and endothelial dysfuction, and are an independent risk factor for occulise vascular disease.

Studies have shown that plasma homocysteine levels are inversely relatied to plasma levels of folate, B12, B6 - the three vitamins involved in the conversion of homocysteine to methionine or cysteine. Supplementation with these vitamins have been shown to reduce circulating levels of homocysteine.

Rare deficiencies in Cystathionine beta-synthase are seen in patients with classic homocystinuria. These individuals experience premature vascular disease.

Question 13

Besides Methionine, what other 3 amino acids form Succinyl CoA?

How do these A.A. convert to Succinyl CoA?

Answer 13

Threonine, Valine and Isoleucine.

Valine and Isoleucine: are branched A.A. that generate propoinyl CoA, which is converted to Succinyl CoA by biotin and vitamin B12.

Threonine: gets dehydrated to alpha-ketoglutyrate, which is converted to propionyl CoA and then Succinyl CoA.

Question 14

What are the 4 amino acids that give form to Acetyl CoA or Acetoacetyl CoA?

Answer 14

Leucine: exclusively ketogenic

Isoleucine: Keto and glucogenic

Lysine: exclusive ketogenic

Tryptopha: Gluco and Ketogenic

Question 15

What are the 3d branched essential amino acids?

Where are these A.A. metabolized?

What are the 3 steps of their catabolism?

Answer 15

Isoleucine, Leucine, and Valine are essential amino acids. They are metabolized by the peripheral tissues (particularly muscle) rather than liver.

Their catabolism involves transamination, oxidative decarboxylation, and dehydrogenation.

Question 16

Explain the 3 steps of branched A.A. catabolism?

Answer 16

Isoleucine, Valine, and leucine go through 3 steps:

Transamination: removal of the amino groups of all 3 amino acids is catalyzed by a single Vitamin B6-requiring enzyme, branched-chain alpha-amino acid aminotransferase.

Oxidative decarboxylation: Removal of the carboxyl group of the alpha-keto acids derived from leucine, valine, and isoleucine is catalyzed by a single multienzyme complex, branched-chain alpha-keto acid dehydrogenase complex. An inherited deficiency of this enzyme results in accumulation of the branched-alpha-keto acid substrate in the urine. (Mapple syrup disease)

Dehydrogenation: Oxidation of the products formed in the above rx yields alpha-beta-unsaturated acyl CoA derivatives.

Question 17

What can cause megaloblastic anemia?

Answer 17

Folate deficiency presents as a megoloblastic anemia due to decrease availability of the TMP (thymidine monophosphate) needed for DNA synthesis.

The active form of folic acid, tetrahydrofolic acid (THF), is produced from folate by dihydrofolate reductase (DHFR) in a two-step rx requiring two moles of NADPH.

Question 18

How is Serine synthesize?

Answer 18

This amino acid arises from 3-phosphoglycerate, an intermediate in glycolysis, which is first oxidized to 3-phosphopyruvate, and then transaminated to 3-phosphoserine. Serine is formed by hydrolysis of the phosphate ester. Serine can also be formed from glycine through transfer of hydroxymethyl group by serine hydroxymethyl transferase.

Question 19

How is Glycine synthesize?

Answer 19

This amino acid is synthesized from serine by removal of a hydroxy-methyl group, also by serine hydroxymethyl transferase.

Question 20

What disease develops from a deficiency in phenylalanine hydroxulase?

Symptoms?

Answer 20

A deficiency in phenylalanine hydroxylase results in the disease of Phenylketonuria (PKU). PKU is the most common clinically encountered inborn error of amino acids metabolism. Accumulation of phenylalanine and deficiency of tyrosine.

Phenylalanine will be elevated in plasma, tissues, urine. Phenylacetate, phenyllactate, and phenylpyruvate which are not normally made in significant amounts in the presence of functional phenylalanine hydroxylase. Give urine a “mousey/musty” odor.

CNS symptoms include mental retardation, failure to walk or talk, seizures, hyperactivity, tremor, miicrocephaly, and failure to grow are charesterisitic found in PKU.

Question 21

What disease other than Albinism shows hypopigmentation?

Answer 21

Patients with phenylketonuria (PKU) often show a deficiency of pigmentation (fair hair, light skin color, and blue eyes) The hydroxylation of tyrosine by tyrosinase, which is the first step oin the formation of the pigment melanin, is competitively inhibited by the high levels of phenylalanine present in PKU.

Question 22

In patients with PKU, what other amino acid besides phenylalanine, becomes an essential that needs to be supplied through diet?

Answer 22

Tyrosine

Question 23

What happens on maternal PKU syndrome?

Answer 23

When women with PKU who are not on a low-phenylalanine diet become pregnant, the offspring are affected with “Maternal PKU syndrome” high blood phenylalanine levels in the mother cause microcephaly, mental retardation, and congenital heart abnormalities in the fetus.

Question 24

What disease arises from branched-chain alpha-keto acid dehydrogenase deficiency?

Answer 24

Maple syrup uine disease (MSUD). branched-chain alpha-keto acid dehydrogenase is an enzyme complex that decarboxylates leucin, isoleucine, and valine.

These amino acids and their corresponding alpha-keto acids accumulate in blood, causing a toxic effect that interferes with brain function.

Question 25

What are pophyrin?

Answer 25

Porphyrins are cyclic compound (linkage of 4 pyrrole rings through methenyl bridges) that readily bind metal ions, usually Fe2+/Fe3+. The most prevalent metalloporphyrin in humans is heme (prosthetic group for hemoglobin, myoglobin, and cytochromes, catalase, and tryptophan pyrrolase). Only type III porphyrins are physiologically importain in humans.

Question 26

What is the committed and rate-controlling step in hepatic porphyrin biosynthesis? Substrate? Enzyme? co-enzyme needed?

Answer 26

Glycine and succinyl CoA condense to form ALA (delta-aminolevulinic acid) in a rx catalyzed by ALA synthase. This reaction requires vitamin **B₆ pyridoxal phosphate** as a coenzyme.

Question 27

What inhibits porphyrin production when it exceeds the availability of globin?

Answer 27

When porphyrin exceeds the availability of globin, heme accumulates and is converted to hemin by the oxidaton of Fe²⁺ to Fe³⁺. **Hemin** decreases the activity of hepatic ALA synthase by causing decreased synthesis of the enzyme, through inhibition of mRNA synthesis and use.

Question 28

If we prescribe a pt. these drugs **griseofuvin** (antifungal agent), **hydontoin**, and **phenobarbital** (anticonvulsants used to treat epilepsy), the patient will have an increase of P450 activity. How will this affect Heme synthesis?

Answer 28

It will increase ALA synthesis by increasing the hepatic ***ALA synthase*** activity. These drugs are metabolized by the microsomal cytochrome P450. In response to these drugs, the synthesis of P450 proteins increases, leading to an enhanced consumption of heme. This in turn, causes a decrese in the concentraition of heme in liver cells, which leads to an increase in the synthesis of ALA synthase and prompts a corresponding increase in ALA synthesis.

Question 29

Why will lead poisoning lead to anemia?

Answer 29

It will block ***ALA dehydratase***, which is extremely sensitive to inhibition by heavy metals ions. The condensation of two molecules of ALA to from prophobilinogen is catalyzed by ALA dehydratase.

Question 30

What are porphorias?

Answer 30

They are rare inhereted or sometimes acquired defects in heme synthesis. This results in the accumulation and increased excretion of porphyrins or porphyrin precursors.

Question 31

Patient presents with urine that is red to brown in natural light, and has skin eruptions. What disease related to A.A. specialized products can be?

Answer 31

**_Chronic porphyria:_** *Porphyria cuatanea tarda*, the most common porphyria, is a chronic disease of the liver and erythroid tissues. The disease is associated with a deficiency in ***uroporphyrinogen decarboxylase.*** Uroporphyrinogen III won't be able to turn into coporporphyrinogen III which is a precursor of Heme. Individuals with an enxyme defect leading to the accumulation of tetrapyrrole intermediates show photosensitivity, that is, their skin itche and burns (pruritis) when exposed to visible light. (superoxides damage membranes, and cause the release of destructive enzymes form lysosomes).

Question 32

What is the heme degradation pathway? What is the enzyme that participates on it?

Answer 32

Bilirubin Glucuronyl-transferase. Takes bilirubin that entered the liver through Bilirubin-albumin complex, and coverts it to Bilirubin Diglucuronide.

Question 33

What happens on Crigler-Najjar I and II / Gilbert syndrome? What happens on Dubin-Johnson syndrome?

Answer 33

Crigler-Najjar I and II syndrome bilirubin can not be turned into bilirubin diglucuronide because the enzyme ***bilirubin glucuronyl-transferase*** is deficient In Dubin-Johnson, there is a deficiency in th eprotein required for transport of conjugated bilirubin out of the liver. (Higher levels on conjugated bilirubin)

Question 34

What are the 3 types of joundice we can encounter?

Answer 34

Hemolytic Jaundice Hepatocellular Jaundice Obstructive Jaundice

Question 35

If a pt. presents with Pyruvate kinase deficiency or glucose-6-dehydrogenase deficiency. How can this cause Jaundice?

Answer 35

Pt. will have massive lysis of RBCs and will produce bilirubin faster that what it can be conjugated in the liver. Hence pt. ends up with ***Hemolytic Jaundice.***

Question 36

Pt. presents with elevated levels of AST, ALT, nausea, dark urine, and its anorexic. What can be the cause of these symptoms?

Answer 36

**Hepatocellular Jaundice:** Damage to liver cells in patients with cirrhosis or hepatatis for instance, can cause unconjugated bilirubin levels to increase in the blood as a result of decrease conjugation. Bilirubin diffuses (leaks) into the blood.