Amino Acid Metab and Urea Cycle Flashcards by brittany gouse

** concentration of free amino acids** is higher in the cell or out of the cell?

intracellular concentration is ocnsiderably higher

this gradient is maintained by active transport of amino acids into cells

How well did you know this?

Not at all

Perfectly

the intracellular/extracellular free AA gradient varies with different AA, the greatest with

glutamate and glutamine.

How well did you know this?

Not at all

Perfectly

** what are the most abundant amino acids in serum.

Glutamine and alanine

How well did you know this?

Not at all

Perfectly

In the body there is about 100g of free amino acids.

how much is glutamate and glutamine?

how much is essential AA?

50% – glutamate, gluatmine

10% – essential AA

How well did you know this?

Not at all

Perfectly

*********

What are the essenital AA?

“Pvt. Tim Hall”

Phenylalnine
Valine
Trptophan

Threonine
Isoleucine
Methionine

Histidine
Arginine
Leucine
Lysine

How well did you know this?

Not at all

Perfectly

____ becomes essential if **methionine is low **

Cysteine

How well did you know this?

Not at all

Perfectly

_____ becomes essential if phenylalanine is low.

tyrosine

How well did you know this?

Not at all

Perfectly

essential AA for growth?

arginine

How well did you know this?

Not at all

Perfectly

inputs into the AA pool are from

dietary protein and proteolysis of cellular protein

How well did you know this?

Not at all

Perfectly

Approximately half the endogenous protein (6-7kg) is associated with

the skeleton and other supporting tissues

(Of which the major protein component is collagen)

How well did you know this?

Not at all

Perfectly

Gastrointestinal inputs

70-100g of dietary protein and 35-200g of endogenous protein from sloshed off____ absorbed daily.

intestinal cells

How well did you know this?

Not at all

Perfectly

Disorders associated with defects in amino acid transport lead to

increased levels of these amino acids in the urine,

How well did you know this?

Not at all

Perfectly

Disorders associated with defects in amino acid transport

prognosis?

these disorders are benign or cause only minor health problems, since amino acids are also absorbed from the intestines as small peptides

How well did you know this?

Not at all

Perfectly

___ separate transporters of AA from the gut into intestinal epithelial cells

FIVE

How well did you know this?

Not at all

Perfectly

transport of amino acids from the gut into intestinal epithelial cell all are ___ symporters

NA or PROTON SYMPORTERS

How well did you know this?

Not at all

Perfectly

High degree of redundancy with ___ since they overlap considerably in their specifity

AA transporters from gut to intestinal epithelial cells

How well did you know this?

Not at all

Perfectly

what is the defect involved in Hartnup’s Disease??

A defect in the transport system for neutral and aromatic amino acids from the gut and the renal tubules

How well did you know this?

Not at all

Perfectly

Hartnup’s Disease sx?

4D’s: Diarrhea, Dermatitis, Dementia, Death)

How well did you know this?

Not at all

Perfectly

Hartnup’s Disease tx?

administration of niacin

How well did you know this?

Not at all

Perfectly

how is Hartnup’s Disease dx?

diarrhea, dermatitis, dementia, death with HIGH LEVELS OF NEUTRAL OR AROMATIC AA IN URINE

How well did you know this?

Not at all

Perfectly

what is the defect in Cysinuria?

A defect in the transport system for basic amino acids and cystine (a disulfide- linked dimer of cysteine) from the gut and the renal tubules.

How well did you know this?

Not at all

Perfectly

Cystinuria sx?

crystals formed by cystine can lead to UTI AND KIDNEY STONES

How well did you know this?

Not at all

Perfectly

Cystinuria tx?

fluids, and administration of the drug penicillamine (reacts with cystine to form a significantly more soluble compound)

How well did you know this?

Not at all

Perfectly

where is trancytosis along the brush border most pronounced?

in infants where it enables them to acquire antibodies from breast milk.

How well did you know this?

Not at all

Perfectly

Cystic Fibrosis Because of a defect in the chloride channels in the pancreatic secretory ducts, what do these pts need to be given?

secretory ducts harden, so need pancreatic enzymes

when is body protein being broken down to free AA?

continuously The **rate of this proteolysis** varies widely between proteins from half lives of a **few minutes to years.**

The urinary levels of ____ can provide a measure of muscle protein breakdown.

**3-methyl histidine** it is liberated when actomyosin is broken down. histidine residues of muscle are methylated posttranslationally

Metabolic breakdown of amino acids to urea and CO2 is a continuous drain. This is reduced during

starvation, but is never turned off.

\_\_\_ and ___ provide complementing essential amino acids.

Grains and beans

Normal nitrogen balance (in a healthy person)

total daily N intake = totai daily N loss (in urine, skin feces)

If **nitrogen losses are less** than intake, the subject is in ____ nitrogen balance

positive

examples of ppl in positive N balance?

children and convalescing adults

**If nitrogen losses** are more than intake, the subject is in ____ nitrogen balance

negative

examples of people in negative N balance?

wasting or starvation

Prolonged negative balance can be fatal if loss of body protein reaches about \_\_\_\_of total body protein.

one-third

Insufficient quantities o**f how many essential amino acids** is adequate to turn an otherwise nml individual into one with a negative nitrogen balance.

just one

In general, ___ proteins are deficient in **lysine, methionine, and tryptophan**

plant

the absence of **lysine** in low-grade cereal proteins, used as a dietary mainstay in many underdeveloped countries can lead to

kwashiorkor syndrome

Free ammonia ion is highly poisonous so the body can move remove **free NH + in three ways.**

1. Glutamate Dehydrogenase 2. Glutamine Synthase 3. Carbamoyl Phosphate Synthase I and II

how Glutamate Dehydrogenase can remove NH4?

combine NH4 with a-ketoglutarate ---\> **puts NH4 in glutamate**

how Glutamine Synthase removes NH4?

NH4 + glutamate ---\> **_glutamine_**

how **Carbamoyl Phosphate Synthase I and II** removes NH4?

difference between Carbamoyl Phosphate Synthase I and II

I. Located in **mitochondria for urea cycle** II. Located in the **cytoplasm** for pyrimidine nucleotide biosynthesis II does not use NH4

what is Transamination?

The transfer of an **amino group** from an AA to an **α-keto acid** to form a new AA and a new keto acid

what is formed with **transamination**?

1. a new AA 2. a new keto acid

\_\_\_\_ an essential cofactor for all transaminations.

Pyridoxal phosphate (vitamin b6):

\_\_\_\_\_ functions as a cofactor in a number of reactions including: a) transaminations b) decarboxylations c) dehydration of ß-hydroxyamino acids d) racemizations of α-amino acids e) removal of H2S from cysteine

Pyridoxine

All ____ appear to have a common enzyme mechanism utilizing pyridoxal phosphate

transaminases

The α-amino groups of at least 12 amino acids are removed by pyridoxal phosphate transaminase

alanine, arginine, asparagine, aspartate, cysteine, isoleucine, leucine, lysine, phenylalanine, tryptophan, tyrosine and valine.

\_\_\_\_ is an efficient way for cells to **send 3 carbon groups back to the liver** to be easily **converted into glucose** while disposing of an NH4 group.

alanine, which can be turned into pyruvate

Most transaminases converge on the amino acid \_\_\_.

glutamate

why is glutamate one of the most abundant AA inside cells

**Most transaminases** converge on the amino acid glutamate.

where does Oxidative Deamination by Glutamate Dehydrogenase?

in the mitocondria

Glutamate dehydrogenase can use what are a cofactor

either oxidized NAD or NADP

Under normal conditions in the liver the ratio of NADPH to NADP is \_\_\_

high the ratio of NADH to NAD is low, **so that there is always cofactor available** to participate in the Oxidative Deamination by Glutamate Dehydrogenase in either the forward or reverse direction.

Glutamate dehydrogenase is activated by? inhibited by?

activated -- adp and gdp inhibited by -- atp and gtp

Glutamate is deaminated mainly in the\_\_\_

liver.

difference in when liver genederates NADH?

If the liver **needs energy** it will generate NADH **_for electron transport._** If it is **energy rich**, it will generate NADPH for **_biosynthetic reaction._**

where are Amino acid oxidases found? what are they found to?

found in the **kidneys and liver** tightly bound to **flavins**

what do Amino acid oxidases convert?

**an amino acid** and a **water** molecule into its corresponding **α-keto acid** and **ammonia.**

direct deamination by dehydratases is facilitated in the aa ____ bc of the chemistry of the hydroxyl side

serine and threonine,

what is The cofactor for both **serine and threonine dehydratase** is

pyridoxal phosphate

**_Homocysteine desulfhydrase i_**s also a **pyridoxal phosphate containing enzyme** that removes both ___ and ____ from homocysteine.

ammonia and sulfur

3 alternate mechanisms for AA deamination

1. **AA oxidases** 2. Direct deamination by **dehydratases** 3. **Desulfhydrases**

how is **α-ketobutyrate** disposed of?

what fatty aci dpathway does vit. b12 catalyze?

b12 catalyzes the last step of the α-ketobutyrate --\> succinyl CoA pathway

\_\_\_release during catabolism of amino acids is toxic and must be constantly removed from the body.

Ammonia

why does the body converts the **_free ammonia_** to **_urea_**

- **the constant excretion of ammonia in the urine** would lead to **drastic changes in blood pH** - **_urea_**, a readily **soluble** and **easily excreted** compound

ammonia and CO2 ---\>

Carbamoylphosphate

ammonia and CO2 ---\> Carbamoylphosphate Enzyme-

carbamoylphosphate synthetase

ammonia and CO2 ---\> Carbamoylphosphate ## Footnote Energy requirement-

Two molecules of ATP

carbamoylphosphate and ornithine ---\> Citrulline enzyme?

ornithine transcarbamoylase (OTC)

ornithine transcarbamoylase is an X-linked gene what rxn is affected with a defect in this pathway

carbamoylphosphate and ornithine ---\> Citrulline ## Footnote via this enzyme

citrulline and aspartate ---\>

Argininosuccinate

citrulline and aspartate ---\> Argininosuccinate Enzyme-

argininosuccinate synthetase.

citrulline and aspartate ---\> Argininosuccinate Energy requirement?

Energy requirement- one molecule of ATP goes to AMP

citrulline and aspartate ---\> Argininosuccinate what is formed?

**PPi** is generated it is degraded by pyrophosphatase

citrulline and **aspartate** ---\> Argininosuccinate where does **asparate** come from?

transamination of oxaloacetate by glutamate.

cleavage of argininosuccinate---\>

Arginine and Fumarate

cleavage of argininosuccinate---\> Arginine and Fumarate Enzyme-

Enzyme- argininosuccinate lyase (argininosuccinase)

cleavage of arginine.---\>

Urea and Ornithine

cleavage of arginine.---\> Urea and Ornithine Enzyme-

arginase

Urea acid cycle \_\_\_\_ \<------\> Urea + 2ADP + 1 AMP + PPi + Fumarate + 2Pi

CO + NH + + 3ATP + Aspartate + 2H O

CO + NH + + 3ATP + Aspartate + 2H O \<------\> \_\_\_\_

Urea + 2ADP + 1 AMP + PPi + Fumarate + 2Pi

what urea cycle enzymes are in the Mitchondria?

carbamoylphosphate synthetase ornithine transcarbamoylase

what urea cycle enzymes are in the Cytosol?

argininosuccinate synthetase argininosuccinate lyase arginase

Urea carries \_\_\_ammonia groups

two ammnoia

Urea Soluble to \_\_\_10M (640g/l)

Why Urea? (4)

* Carries two ammonia groups * Soluble to \>10M (640g/l) * Non protonatable-10% solution pH 7.2 * Low reactivity (inert)

KEY STEPS OF THE UREA CYCLE ARE CARRIED OUT IN THE MITOCHONDRIA?

1. **NH4+ + CO2 + 2 A TP** ---\> **CARBAMOYL PHOSPHA TE** 2. **ORNITHINE** ---\> **CITRULLINE**

Protein free diet- urea excretion accounts for only \_\_\_% of the total urinary nitrogen as compared to 80% in a normal diet.

with a ___ diet, levels of **urea cycle enzymes** decline

protein free diet

High Protein diet- or in starvation, urea cycle enzymes

increase several fold. since gluconeogenesis from amino acids is high

symptom of most of the diseases caused by defective urea cycle enzymes?

An accumulation o**f ammonia** in the **blood**

\_\_\_ deficiency is the most common urea cycle disorder

OTC \* due to its presence on the X chromosome

Mental Retardation is seen with what urea acid disorder?

Citrullinemia defect in Argininosuccinate Synthetase

**Argininosuccinic aciduria** defect is in what enzyme? what is seen in the blood?

defect -- Argininosuccinase blood -- NH4 and Argininosuccinic Acid urine -- Arginosuccinic Acid

**Hyper- ammoniemia** defect is in what enzyme? what is seen in the blood?

enzyme -- Carbamoyl Phosphate Synthase blood -- High NH4

**Arginiemia** defect is in what enzyme? what is seen in the blood? defect?

defect -- Arginase blood -- High NH4 and **Arginine** urine -- Arg, L ys, Orn

**Hyper- ornithinemia** defect is in what enzyme? what is seen in the blood? urine?

defect --Ornithine Transcarbamylase blood -- High NH4, orotate and Ornithine urine -- Ornithine

Treatment of urea cycle disorders usually includes

low protein diet that is supplemented with arginine or citrulline since **arginine usually becomes essential in these patients.** administration of sodium benzoate and sodium phenylacetate