Lecture 8 Amino Acids

Question 1

Nitrogen Metabolism

Answer 1

Amino acid synth, amino degradation, derivatives of AA, urea cycle.

Question 2

Energy used for

Answer 2

Heat, mechanical movement, electrical work, chemical energy can be stored or used as food.

Question 3

Metabolism

Answer 3

Release of energy, water, CO2.

Question 4

Anabolism

Answer 4

Building

Question 5

Catabolism

Answer 5

Breaking

Question 6

Anabolic reactions

Answer 6

Glucose to glycogen, Glycerol+fatty acids to triglycerides, amino acids to proteins. Most of this happens in the liver

Question 7

Catabolism

Answer 7

Glycogen to glucose, triglycerides to glycerol + fatty acids, proteins to AAs (obtain essential AAs this way). Most of this happens in the liver

Question 8

AA breakdown

Answer 8

Ammonia byproduct.

Question 9

Digestion

Answer 9

Carbs - glucose (+other monosaccharides)
Fats - triglycerides (glycerol, fatty acids)
Proteins - aas

Question 10

Using aas as energy

Answer 10

First you have to get rid of nitrogen. AAs feed into becoming pyruvate (3 carbon - used for glucose production), acetyl CoA (2 carbon, not for glucose). TCA cycle and ETC can be used later from these.

Question 11

Breaking down nutrients

Answer 11

AAs and glycerol can be converted to pyruvate (glucose later). Needed for CNS and RBCs. Lean tissue goes when body runs out of glucose. Adequate carbs prevent this. Fatty acids are converted to Acetyl-CoA (not for glucose).

Question 12

Pyruvate’s Options

Answer 12

Quick energy - convert to lactate (anaerobic). Sustained for just a few minutes.
SLower energy - convert to acetyl CoA - aerobic.

Question 13

Cori Cycle

Answer 13

Lactic acid travels to the liver

–the liver converts it back to glucose –This is called the Cori cycle

Question 14

Pyruvate to Acetyl CoA

Answer 14

If o2 is available. Pyruvate enters mitochondria, –produce 2 acetyl CoA.

Question 15

Glucogenic AAs

Answer 15

Convert to pyruvate

Question 16

Ketogenic AAs

Answer 16

COnvert to acetyl CoA

Question 17

AAs breakdown

Answer 17

they can be used for energy or converted to fatty acids and stored as triglyceride.
–Some enter the TCA cycle directly

Question 18

Dietary protein

Answer 18

Dietary protein is the main source of amino acid. In the process of digestion, proteins are broken down to free aa in the gastrointestinal tract. The resulting alpha-keto acid is then used as fuel, or as a biosynthetic intermediate.
Unlike carbohydrates and lipids, aa do not have a dedicated storage form equivalent to glycogen or fat.
When aa are metabolized, the resulting excess nitrogen must be excreted.

Question 19

Transamination

Answer 19

Remove amine group from AAs in liver.

Question 20

Protein digestion

Answer 20

Stomach - HCl breaks down, denatures, small peptides. Intestines - other proteases get it to AAs and some dipeptides. Transport across small intestine lining.

Question 21

AAs to body proteins, Glucose to glycogen

Answer 21

Reversible.

Question 22

AA catabolsim

Answer 22

Removal of amino group, use of nitrogen in synth of new nitrogen compounds, passage of nitrogen into urea cycle, incorporation of carbon atoms into compounds for CAC cycle.

Question 23

Our body does not store

Answer 23

Nitrogen containing compounds.

Question 24

Transaminase

Answer 24

Use alpha ketoglutarate as amino group nitrogen acceptor. This is converted to glutamate.

Question 25

Transaminase

Answer 25

Exchange amino group with carbonyl. No net loss of N2.

Question 26

Alanine can be converted to

Answer 26

pyruvate and glutamate from alanine and oxoglutarate (all 3 carbon atoms, all of these conversion reactions are bidirectional).

Question 27

Glutamate

Answer 27

All amino groups go through glutamate. Transaminase reactions are easily reversible. Concentrations determine where it goes.

Question 28

Transaminases

Answer 28

Equilibriate amino groups among available alpha keto acids.

Question 29

Nitrogen

Answer 29

Although the amino N of one amino acid can be used to synthesize another amino acid, N must be obtained in the diet as amino acids (proteins). Proceed through urea cycle before excretion (processing occurs in liver).

Question 30

Urea Cycle

Answer 30

Ammonia is highly toxic to living organisms and must be eliminated safely. Fish excrete ammonia through their gills directly into the surrounding water and mammals converts ammonia to non-toxic urea via the urea cycle. The conversion of ammonia to urea takes place in the liver. From there urea is transported to the kidneys and transferred to urine for excretion.

Question 31

AA degradation

Answer 31

Transamination Oxidative Deamination Removal of a molecule of water by a dehydratase

Question 32

Oxidative Deamination

Answer 32

he oxidative removal of the amino group, resulting in keto acids and ammonia

Question 33

Removal of a molecule of water by a dehydratase

Answer 33

serine or threonine dyhydratase; this reaction produces an unstable, imine intermediate that hydrolyzes spontaneously to yield an α-keto acid and ammonia

Question 34

Glutamate Dehydrogenase

Answer 34

Catalyzes rxn that removes N from the amino acid pool. Takes N from glutamate to form alpha-ketoglutarate (now this can go back to grab a different ammonia).

Question 35

Serine Dehydratase

Answer 35

Pyridoxal phosphate dependent Product is pyruvate Remove H20, leaving unstable intermediate. This will spontaneously remove ammonia and form pyruvate.

Question 36

Serum urea

Answer 36

BUN (blood urea nitrogen). Monitored in patients with amino acid metabolism disorders or renal problems. Measure the action of urease by monitoring ammonia product with a color reagent.

Question 37

Monosodium Glutamate - MSG

Answer 37

Food additive. Can cause weakness, tingling and a sensation of warmth in the face and upper torso. Symptoms generally last about 30 minutes. No permanent damage, but could trigger bronchospasms (asthma).

Question 38

Glutamic acid

Answer 38

Also a neurotransmitter - can be decarboxylated to form GABA, another neurotransmitter.

Question 39

Deamination

Answer 39

Oxidative, nonoxidative

Question 40

Alanine as a carrier

Answer 40

Transported from peripheral tissues to liver, converted to pyruvate with nitrogen incorporated into urea Pyrovate can be used to produce glucose (gluconeogenesis) This glucose-alanine cycle allows the net conversion of amino acid carbons to glucose Carbons are returned to peripheral tissues as glucose Alanine and glutamine are released in similar amounts from muscle Account for about 50% or amino acids released by muscle into the blood

Question 41

Alanine and Glutamine flow

Answer 41

The amount of alanine and glutamine released far exceeds the proportion of these Aas in muscle proteins Large amounts of remodeling of protein-derived amno acids occurs by transaminations

Question 42

Nitrogen excretion

Answer 42

``` No storage Need to ingest excess Ammonia toxic NH4+ -Excrete excess ``` ``` Ammonia, NH4+ Aquatic animals (ammonolitic organism) Uric Acid Birds and reptiles (uricotelic organisms) Urea, H2N-(CO)-NH2 Terrestrial vertabrates (ureotelic organisms) ```

Question 43

Aquatic animals | ammonolitic organism

Answer 43

Ammonia, NH4+

Question 44

Birds and reptiles | uricotelic organisms

Answer 44

Uric Acid

Question 45

Terrestrial vertabrates | ureotelic organisms

Answer 45

Urea, H2N-(CO)-NH2

Question 46

Urea cycle

Answer 46

First metabolic cycle detected. Krebs & Henseleit. Urea H2N-(CO)-NH2, 2 nitrogens 1 from ammonia through carbamoyl phosphate NH3 + HCO3- + 2ATP 1 from Aspartic acid α-ketoglutarate + NH4+ + NADH + H+ Carbon from bicarbonate (unfixed) Urea cycle also excretes bicarbonate breakdown product of carboxylic acids **Starts in mito**

Question 47

Inherited disorders of urea cycle

Answer 47

Loss of cycle catastrophic Ammonia toxic to brain coma See with liver failure Do not see genetic diseases with total loss Genetic partial deficiencies retardation Treatment with low protein diets Supplement with keto-acids Mops up excess NH3 If choose wisely, can get essential amino acids made (e.g., α-ketoisovalerate valine)

Question 48

Treatment of genetic deficiencies in urea cycle enzymes

Answer 48

Aromatic groups can help

Question 49

AA formation

Answer 49

First step required | transamination→ glutamate or aspartate

Question 50

Glucogenic

Answer 50

Increase glucose - certain AAs are both glucogenic and ketogenic.

Question 51

Ketogenic

Answer 51

Increase ketone bodies.

Question 52

Maple syrup urine disease

Answer 52

Inherited. Loss of the α-amino group, followed by oxidative decarboxylation of the resulting α-keto acid to produce a CoA derivative Decarboxylation catalyzed by branched-chain keto acid decarboxylase (IM of mitochondria) Untreated lead to both physical and mental retardation Defect can be managed with a low-protein diet or modified diet or supplementation with high doses of thiamine pyrophosphate

Question 53

Phenylketonuria

Answer 53

Deficiency of phenylalanine hydroxylase. Untreated leads to excretion of phenylpyruvate and phenyllactate. Can result in severe retardation. Individuals, very light skin, unusual gait, stance

Question 54

Alkaptonuria (black urine disease)

Answer 54

Deficiency in phenylalanine-tyrosine pathway, the enzyme that catabolizes the oxidation of homogentisic acid Homogentisic acid accumulates and is excreted in the in urine (1 in 1,000,000 births). This compound gives urine a dark color Individual: dark pigment in cartilage tissue, with subsequent tissue damage, and severe arthritis Only symptomatic relief

Question 55

Albinism

Answer 55

Lack of pigmentation (amino acid pathways). Blue eyes, light blond hair. Lack enzyme tyrosinase.

Question 56

Tyrosinase

Answer 56

2-step hydroxylation of tyrosine to dihydroxyphenylalanie (DOPA) and further oxidation to a quinone, a precursor of melanin

Question 57

LSD

Answer 57

derived from tryptophan and serotonin.

Question 58

Polyamines

Answer 58

Exactly what it sounds like. Ornithine is a precursor. Ornithine decarboxylase upregulated in a wide variety of cancers - ODC is the rate limiting step in polyamine synthesis. Drugs targeting ODC have been used in cancer treatment. In essence, inhibit polyamines, inhibit growth.