Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/136

Click to flip

136 Cards in this Set

  • Front
  • Back
Primary synthesis and catabolism site for amino acids is....
Liver
List the two pathways that can synthesize glutamate?
(1) Reductive amination (from alpha-ketogluterate using GDH).

(2) Transfer of amino group by transaminase or amino transferase.
Which enzyme is used in the reducting amination of alpha-ketogluterate?
Glutemate Dehydrogenase
How is glutamine synthesized?
By amination of glutamate using Gltamine synthetase (nitrogen group comes from NH4)
How do you get glutamine from alpha-ketogluterate?
Alpha-ketogluterate ---> glutamate (using GDH or transaminase) ---> Glutamne (using Glutamate synthetase)
How is Aspargine synthesis similar/different to Glutamine synthesis?
Both reactions are amination reaction.

Asparging gets its nitrogen group from Glutamine WHILE glutamine gets its nitrogen group from NH4.
How is Proline synthesized?
By cyclization and reduction of glutamate.
List the two ways to synthesize Serine.
(1) From 3-phosphoglycerate By oxidation and transamination.

(2) From Glycine - through transfer of a hydroxymethyl group.
List four ways Glycine can be synthesized?
(1) From Serine - Transfer of hydroxymethyl group

(2) Transamination of glyoxylate by glycine aminotransferase

(3) Choline

(4) From CO2 and NH4 - by mitochondrial glycine synthase complex.
Cysteine is synthesized from...
Methionine and Serine

(Methionine ---> Homocysteine (+ Serine using Cystathionine-b synthase) ---> Cystathionine --> Cysteine and Alpha-Ketobutyrate
How is tyrosine synthesized?
Tyrosine is synthesized from Phenylalanine (using Phenylalanine hydroxylase)
Phenylalanine hydroxylase requires...
Tetrahydrobiopterin and O2.
Dihydrobiopterin
Forms tetrahydrobipterin using NADPH.

BH4 is the coenzyme used in synthesis of Tyrosine.
List the precursors for following amino acids...

Glutamate
Aspartate
Asparigine
Glutamine
Tyrosine
Cysteine
Glycine
Serine
Proline
Alanine
Glutamate - Alpha-ketoglut
Aspartate - Oxaloacetate
Asparigine - Aspartate
Glutamine - Glutamate
Tyrosine - Phenylalanine
Cysteine - Methionine, Serine
Glycine - Serine, Glyxoylate, Choline, Co2, NH4
Serine - 3phosphoglycerate, glycine
Proline -Glutamate
Alanine - Pyruvate
Melanin is synthesized from..
Tyrosine
List two deficiencies that can give rise to PKU.
(1) Deficiency in Phenyalanine Hydroxylase

(2) Deficiency in BH2 reductase
BH4 is used to...
(1) Convert L-phenylalanine to Tyrosine

(2) Synthesize catecholamines from Tyrosine
(3) Synthesis of Serotonin from tryptophan.
Why does Vitamin C deficiency lead to Scurvy?
Vitamin C --> Hydroxylysine

Hydroxylysine is present mostly in collagen. Hence, Vitamin C deficieny leads to spongy gums, loose teeth, fragile blood vessels etc..(SCURVY)
Which substrates are required to synthesize hydroxyproline?
Vitamin C, Fe, O2 and Alpha-ketogluterate
Tetrahydrofolate consists of...
(1) Pteridine ring
(2) p-aminobenzoic acid
(3) Glutamate (one or chain)
List two competetive inhibitors of DNA synthesis..
(1) Sulfanilamide (inhibit synthesis of folic acid in microorganisms)

(2) Methotrexate - Comptetively inhibits dihydrofolate reductase (used to treat cancer)
Methotrexate
A folic acid analogue that competitively inhibits dihydrofolate reductase.

Used to treat cancer (because it stops DNA replication)
Megaloblastic anemia
Caused by diminished DNA synthesis.

Result of Folic acid deficiency.
Homocystinuria
Due to the deficieny of Cystathionine Synthase.

Results in vascular diseases, death by MI, stroke or pulmonary embolus.
Cystathioninuria
Due to deficiency of gama-cysathionase.

Results in high levels of cystathionine.
Methylated homocystein is...
Methionine.
List the two major pathways to remove L-Homocysteine.
(1) L-Homocysteine to Methionine (requied TH4 and Vitamin B12)

(2) Formation of Cysteine (requires Vitamin B6)
L-Homocysteine synthesis
From Methionine

Methionine (using SAM) ---> S-adenosylhomocysteine ---> L-Homocysteine
Vitamin B12 structure
Cobalt COVALENTLY bound to Carbons of the Corrin ring.
Pernicious Anemia
Autoimmune destruction of the gastric parietal cells which are responsible for synthesis of glycoprotein called Intrinsic factor (B12 deficiency).

Treated with oral B12 (Cobalamin)
Describe folate trap hypothesis.
L-Homocysteine + N5-Methly THF ---> Met + THF

B12 deficieny will stop above reaction. Hence, THF is in the N5-Methly THF form.

This results in insufficient nucleotide and DNA synthesis.
Why should megaloblastic anemia be treated with Folic acid and Vitamin B12?
Because these two are required for synthesis of Methionine
Amino Acid pool
Total Protein in body..
Protein turnover
100g
12Kg (in 70kg man)
300 to 400g/day
Describe Ubiquitination
Tagging of traget protein with Ubiquitin (Carboxyl group of Glycine on Ubiquitin binding to amino group of Serine of the protein).

Three enzymes are involved
E1 - Ubiquitin activating enzyme
E2 - Ubiquitin Conjugating enzyme
E3 - Ubiquitin Protein Ligase
Endogenous proteins are degraded by...

Exogenous proteins are degraded by...
Ubiquitin-Proteasome Proteolytic pathway

Lysosomes
Cathespins

Types
A group of lysosomal proteinases.

B and L - Cysteine proteases
D - Aspartic acid protease (like pepsin)
Calpains
Ca+2 dependent thiol proteases
Kwashiorkor
Protein depravation is larger than reduction in total calories.

Show signs of edema, inadequate growth, skin lesions, plump belly (due to edema)
Marasmus
When calorie deprivation is greater than reduction in protein (protein can't be converted to calories appropriately)
Gastric secretions consist of..
Gastric acid (HCL) and Pepsin
Gastric acid secretion is stimulated by...
Histamine (a derivating of histadine)
Pepsin
Released by chief cells of intestine as Pepsinogen.

Pepsinogen is converte to Pepsin by HCL or other pepsin molecules.
Cleavage specificity for..

Trypsin

Chymotrypsin

Elastase

Carboxypeptidase A

Carboxypeptidase B
Arg and Lysine

Trp, Tyr, Phe, Met and Leu

Ala, Gly and Ser

Ala, Ile, Leu, Val

Arg, Lys
Two polypeptide hormones of intestine are..
Cholecystokinin and Secretin
Fuctions of...

Cholycystokinin

Secretin
Promotes zymogen secretion by pancreas.

Promotes pancreatic juice secretion to neutralize stomach acid.
Trypsin synthesis is stimulated by...

Trypsin activates..
Enteropepdiases (synthesized by intestinal mucosal cell).

Trypsin activates all other pancreatic zymogens.
Enteropeptidase

Aminopeptidase
Cleaves zymogens to active enzymes.

Exopeptidase that cleaves at N-terminal to produce free AA and smaller peptides.
Amino acid uptake into intestinal epithelial cells..

Two types of transports
Via Cotransport

SLC6A19 - Neutral Aminoacids (All but Lysine, Arg, Pro, Cys, Glu)

SLC3A1/SCL7A9 - Dibasic amino acids (Lys, Arg, Cys)
Hartnup's disease
Caused by defect in SLC6A9 - Neutral amino acid transported.

Tryptophan (hence Niacin) deficienly. Causes Pellagra like symptoms.
Example of selenoprotein...
Glutathione peroxidase
Gamma - Glutamyl cycle
Tranport of amino acids into the intestinal cells.

Requires 3ATPs

Primarily in renal system.

Important for synthesis of Glutathione.
5-Oxoprolinuria
Due to the deficiency in GSH-Synthetase. Also associated with gamma-glutamyl cycle (amino acid absorption system)
Aminotrnasferase
Transfer a-amino group to a-ketogluterate to form Glutamate.

Part of the AA degradation process.

Aminotranferases are named after the amino group donor (ALT and AST).
Which coenzyme is required by all aminotransferase?
PLP (pyridoxal phosphate - derivative of Vitamin B6)
Pyridoxal phosphate
Coenzyme required in aminotransferase reactions.
Two major steps of amino acid degradation are..
(1) Transamination (Using aminotransferases - ALT, AST) - Funnel amino groups to Glutamate.

(2) Glutamate Dehydrogenase - Amino group to Urea
Glutamate Dehydrogenase

Type of reaction...
Occure in..
Coenzymes..
Oxidative deaminaion

Liver and Kidney

NAD (loss of ammonia) or NADPH (gain of ammonia)
Normal ammonia level
10-20ug/dL
Ammonia is transported in the blood as..
Glutamine (Glu + ammonia) - synthesized using glutamine synthetase.

Alanine (transamination of pyruvate to alanine - Glu + Pyruvate to give alanine)
Glutaminase versus Glutamate Dehydrogenase...
Both used in liver to synthesize ammonia.

Glutaminase - Produce Ammonia that came from glutamine

Glutamate dehydrogenase - Produce from glutamate (alanine that came from muscle)
Ureotelic

Uricotelic

Ammonotelic
Ureotelic - Excrete urea into their urine (human and land mammals)

Uricotelic - Excrete uric acid (bird)

Ammonotelic - Ammonia diffuses out of the body (fish)
Uric Acid structure
(1) One ammonia from circulation
(2) Carbon from CO2
(3) Second ammonia from Aspartate

Meaning, both ammonia come from Glutamate (remember how Aspartate is synthesized)
List two pathways that can transfer Ammonia to liver..
(1) Glutamine Synthetase and Glutaminase

(2) Glucose-Alanine cycle
What is the primary regulatory step for urea cycle?
Carbamoyl Phosphate Synthetase I (step 1 of urea cycle)
Allosteric activator of urea cycle step 1?
N-Acetylglutamate
How many moles of ATP are required for Carbamoyl-P synthesis?
2 mol ATP (one of which serves as Phosphoryl donor)
1st step of Urea cycle..

Enzyme
Allosteric activator
Substrates
Enzyme- Mitochondrial Carbomoyl-P Synthetase I

Allosteric Activator - N-AcetylGlutamate

Substrates - ATP, CO2 and NH4
Carbamoyl Synthetase II
Found in cytosol.

Uses Glutamine as nitrogen source.

Functions in pyrimidine biosythesis.
Enzyme for Urea Cycle step 2
L-Ornithine Transcarbamoylase

Transfers carbamoyl group to L-Ornithine and makes L-citrullin.
Enzyme for step 3 in urea cycle.

Energy expenditure...
Argininosuccinate synthetase

Forms ArgininoSuccinate by adding Aspartate to L-Citrulline. (Links them via amino group of aspartate)

One ATP converted to AMP.
Argininosuccinase
Forms arginine and fumarate by cleaving Argininosuccinate.
Liver Arginase
Cleaves Arginine to form Urea and Ornithine. (cleavage at guanidine group of arginine)
List two inhibitors of Arginase
Ornithine and Lysine (compete with Arginine to bind to Arginase)
Where does the two amino group come from for Urea cycle?
Free NH3 (Glutamate is the precursor - oxidative decarboxylation)

Aspartate (Glutamate is precursor - Transamination of Asp by AST)
Cause of hyperammonemia type I
Deficiency in Carbamoyl-P Synthetase I.
Defect in Ornithine transporter results in...
HHH

Hyperammonemia, Hyperornithinemia

Homocitrullinuria (because carbamoyl-P carbamoylates Lysine to homocitrulline.)
How and When is Homocitrullin synthesized?
When - Ornithine is unavailable (ornithine transport defect)

How - Carbamoyl-P carbamoylates Lysine and Homocitrullin is formed.
Hyperammonemia Type II
OrnithineTranscarbamoylase defect
Which compound binds covalently to Glutamine for its removal (when urea cycle is not working)?
Phenylacetate (and forms phenylacetylglutamine, which can be excreted in urine)
Which AA catabolism lead to oxaloacetate?
Aspargine (Asparginase)
Aspartate (Transamination)
Which AA catabolism leads to alpha-ketogluterate?
HGAP

Histidine (coverted to glutamate by histadase)
Glutamine (Glu via glutaminase)
Glutamate (via GDH)
Proline (oxidized to Glu)
Arginine (converted to Ornithine via Arginase. Ornithine is converted to alpha-ketogluterate)
List the AA that form pyruvate..
Alanine
Serine
Glycine
Cystine
Threonine
Phenylalanine breakdown..
(1) Hydrolyzed to Tyrosine
(2) Tyrosine forms fumarate and acetoacetate.

Hence, they are both ketogenic and glucogenic.
Which AA form fumarate?
Phenylalanine and Tyrosin
Alkaptonuria
Caused by defect in tyrosine metabolism.

Deficiency in homogenistic acid oxidase, resulting in accumulation of homogenistic acid.
Gamma-cystathionase
Used to synthesize cysteine from cystathionine. (vitamin B6 is used as cofactor)
cystathionase synthase
used to synthesize cystathionine from l-homocysteine. (vitamin B6 is a cofactor)
Intrinsic factor
A glycoprotein produced by gastric parietal cell.

It is necessary to absorb vitamin B12.
N-Acetylglutamate synthetase is activated by...
Arginine
Which amino acid can be converted to Pyruvate and Succinyl CoA
Threonine
List 4 amino acids that are both ketogenic and glucogenic.
Phenylalanine, Tyrosine (forms fumarate and acetoacetate)

Isoleucine (forms succinylCoA and acetoacetateCoA)

Tryptophan (acetoacetylCoA and one-carbon to folate)
List two ketogenic amino acids.
Leucine
Lysine
Explain serine degradation...
Using Serine dehyrdratase, serine is transferred into Pyruvate.

Using N5-N10MehtleneTHF, serine is transferred to Gly. Gly is converted to CO2 and NH3 using Glycine Synthase Complex in liver mito.
Glycine Synthase Complex
Splits Gly into CO2 and NH4 in the liver mito.
List the enzymes involved in the catabolism of branched chain amino acids.
(1) Branched chain a-amino acid aminotransferase

(2) Branched chain a-ketoacid dehydrogenase comples (defect in this enzyme causes maple syrup urine syndrome)

(2) Oxidative dehydrogenation
What are the products of the three branched Amino acid catabolism?
Isoleucine - (longest name) Acetyl CoA and Succinyl CoA

Leucine (midlength name) - Acetyl CoA

Valine (shortest name) - Succinyl CoA (1-C unit)
Which enzyme is required to convert Histidine to Histamine
Broad specificity L-amino acid decarboxylase
Which amino acids form creatine?
Glycine
Arginine
Methionine
Which amino acid forms NO? Describe the pathway.
Arigine --> NO + L-Citrullin

Reaction catalyzed by NO synthase.

NADPH required.
Which amino acid gives rise to Serotonin.

(compare this with Catecholamine synthesis)
Tryptophan.

(Try ---> 5-Hydroxy-Try --> Serotonin)

E1 - Hydroxylase
E2 - Decarboxylase
Melatonin is formed from..
Serotonin
Melotonin is involved in regulating
circadian cycle.
Dopamine is synthesized from...
Tyrosine
Explain Epi synthesis..
Tyr ---> Dopa ---> Dopamine ---> NE ---> Epi

E1 - Hydroxylase (BH4->BH2)
E2 - Decarboxylase(->CO2)
E3 - Dopamine-B-Hydroxylase
E4 - SAM
Precursor of malnin
Tyrosine
Complete albinism results from deficiency in...
tyrosinase.
Thryoid hormone formation
Iodination of tyrosine forms TH.
Glycine is used to synthesize
creatine, heme and purines.
Serine participates in synthesis of
Purine
Sphingosine
Pyrimidine
Methionine contributes to the synthesis of
SAM
Spermine
Spermidine
Alternative chemical names...

Adenine
Guanine
Hypoxanthine
Xanthine
Adenine - 6-aminopurine
Guanine - 2-amino, 6-oxypurine
Hypoxanthie - 6-oxypurine
Xanthine - 2,6-dioxypurine
Exocylic nitrogens are on which three amino acids
Adenine, Guanine and Cytosine
Alternate names...

Cytosine
Uracil
Thymine
Cytosine - 2-oxy,4-aminopyrimidine

Uracil - 2,4-dioxypyrimidine

Thymine - 2,4-dioxy, 5-methylpyrimidine
How does phosphates bind to ribose (what kind of bond)?
Ester bond
How does ribose bind to the base?
N-Glycosidic bond
Which base does not have a nucleoside form
Xanthine (2,6-dioxypurine)
How are PO4 group attachements to nucleosides different for..

Biosynthetic substrates and
Degradation products
Biosynthetic products - Have PO4 bound to 5' carbon.

Degradation products - Have PO4 bound to 2',3' or 5' carbons.
Which amino acids are used in the synthesis of IMP from Ribose-5P? (to what degree).
2Gln and Asp - provide a amino group.

Gly - is entirely used.
In IMP synthesis, which steps have...

Amino group donor..
Carbon donor...
Glycine donor...
Amino group donor - 1 and 4 (gln) and 7 (asp)

Carbon donor - steps 3 and 9 (THF)

Glycine donor (2)
What is the action of

PRPP Synthase (ribose phosphpate pyrophosphokinase)
Synthesize 5-Phosporibosyl-1-Pyrophosphpate.

(ribose5P + ATP --> 5-phosphoribosyl-1pyrophostate)
Which amino acids provide carbons 1, 3, 7 and 9 to purines
1 - Aspartate
3 and 9 - Glutamine
7 - Glycine
What is the control step in the synthesis of IMP?
Glutamine-PRPP aminotransferase enzyme step.

PRPP --> 5-phosphoribosyl-1amine.

(in this step, amino group from glutamine is transferred to the 1 carbon of PRPP. Pyrophosphate is released ,which is quickly dehydrolyzed so that this step is irreversible.)
List two glutamine analogous..
DON
Azaserine
How does orotate receive a Ribose-P in the UMP synthesis?

OMP is decarboxylated via ____eyzyme to _____.
Orotate --> OMP (via - Orotate Phosphoribosyl Transferase) Group from PRPP

Via Orotidylate decarboxylase to UMP.
Which enzyme in the pyrimidine synthesis is in the mito?
Dihydroorotase Dehydrogenase (to go from Dihydroorotate to Orotate)
Which step the control step in pyrimidine synthesis?

Positive and negative feedback...
Carbamoyl-P Synthase II.

Activated by...PRPP
Inhibited by....UTP
Function of ATC'ase.

Stimulated by...(in bacteria)
Inhibited by...(in bacteria)

Inhibited by...(in humans)
Aspartate Transcarbamoylase

Transport carbamoyl group from Carbamoyl phosphate group to Aspartate and forma N-Carbamoylaspartate

Stimulated by ATP
Inhibited by CTP

PALA - N-Phosphoacetyla L-Aspartate
Which step keeps the balance between pyrimidine and purine in the pyrimidine synthesis?

How?
CTP Synthetase step (last step).

Allosterically activated by GTP and inhibited by CTP
Which steps in Pyrimidine synthesis require...

ATP
Amino Acids
ATP - steps 1(2), kinase step (2), CTP Synthetase step

Gln (step 1 and 7), Aspartate (step 2)
Orotic Aciduria
Due to defieciency in UMP-Synthetase.

Accumulation of Orotate (orotic acid in urine).

Treated by Uracil/Uridine rich diet.
Pyrimidine synthesis regulation...

(1) By pyrimidine levels
(2) By Purine levels
(1) 2much UTP - Inhibit CPSII
2much CTP - Inhibit cytidylate synthetase

(2) 2much GTP - Activate cytidylate synthetase
2much PRPP - Activate CPSII
Which enzyme do these drugs work on?

PALA
5-Azaorotate
6-Azauridine
PALA - ATCase
5-Azaorotate - Orotate Phosphoribosyl Transferase
6-Azauridine - Orotidylate Decarboxylase
Describe following enzymes and their specificity.

UMP Kinase, GMP Kinase, TMP Kinase, CMP Kinase

Nucleoside Diphosphate Kinase

Adenylate Kinase
These kinases are to go from Monophosphate to diphosphate. (oxy or deoxy). Thymine is only in deoxy form.

To go from Diphosphtates to triphosphate (for any base).

To go from AMP -> ADP -> ATP (oxy or deoxy form)
Which enzyme is used to synthesize dNDP from rNDP?

How is this enzyme kept in the reduced state?
Ribonucleotide reductase.

Kept in reduced state using...
Glutaredoxin/Glutathione AND
Thioredoxin/FADH2
Describe Ribonucleotide Reductase
Function: rNDP -> dNDP
Structure - 2 R1 and 2 R2 sites
R2 - Has ferric iron and Tyrosine radical
R1 -
Primary Regulation (ON-OFF) site - ON (ATP) OFF (dATP)

Substrate specifity site -
1.ATP - favors (dCDP, dUDP --->dTTP)
2.dTTP - favors (dGDP --> dGTP)
3. dGTP - favors (dADP ---> dATP)
4. dATP - turns OFF
Which base is not found in the the Oxy form?
Thymine