SChmidt 3 lectures

Question 1

List the esstential AA

Answer 1

PVT TIM HALL
Phenylalanine
Valine
Threonine
Tryptophan
Isoleucine
Methionine
Histidine
Arginine***
Lysine
Leucine

Arigine is nonesstential but in periods of growth its essential.

Question 2

Nonessential AA

Answer 2

AAACGGGPS

ALanine

Arginine

Aspartate

Cysteine

Glutamate

Glutamine

Glycine

Proline

Serine

Question 3

AA that are JUST ketogenic

What does this mean?

Answer 3

Leucine and Lysine

There carbon skelteon becomes acetyl CoA or acetoacetate which CAN”T MAKE OAA which is needed for gluconeogenesis. Since they are two carbon residue they lose both as CO2.

They can enter the TCA cylcye, converted to ketone bodies, or converted to FA

Question 4

Which AA are both Glucogenic and Ketogenic

Answer 4

Tyrosin, phenylalanine, tryptophan

Question 5

Which AA are just glucogenic. Where do they enter the cycle? How are they used

Answer 5

Alanine

Arginine

Aspargaine

Cystine

Glutamate

Glutamine

Glycine

Proline

Sereine

Hisitidine

Methionine

Threonin

Valine

They are degradaed to pyruvate or one of the TCA intermeidates and then become OAA to phosphenolpyruvate and strart gluconeogenosis. When blood glucose are low, AA being broken down are the major source of energy.

Question 6

Functions of Amintransferases

Answer 6

they catalyze the transfer of an amino group from one carbon skeleton to another. They are found in cells throughout the body but mostly in liver and kidney and muscle

Two most important aminotransferase are ALT and AST

Question 7

Prodcudts of ALT and AST

Answer 7

This process is called transaminiation-chemical transfer between two chemical moelcules an amino group. .

ALT transfer the amino group from alanine to alpha-ketoglutarate making pyruvate and glutamate/. This is reversible but in AA catabolism goes towards glutamate.

AST- transfer amino group from asparate to alpha ketoglutarate making OAA and glutamate. This is reversible as well

Question 8

Explain the alanine glucose cycle

Answer 8

Mainly in skseltal msucle but during intense excerise branched AA are released and their carbon backbones are used for energy and their N is used to make alanine. Alanine brings the carbona nd nitrogen to the liver and transfer its NH3 to alpha ketoglutarate and becoes pyruvate which can go into gluconeogensis for energy!

Question 9

What is the cofactor for aminotransferases

Answer 9

Pyridoxal phosphate (functional form of B6)

Question 10

When would you degrade AA? Sytnehsis?

Answer 10

AA degradation (through removal of the amino groups), as would be the case aftereating a protein-rich meal)


Biosynthesis through the addition of amino groups to the carbon skeletons of α-keto acids, as when the supply of AA from the diet is not adequate to meet the needs of the
cells

Question 11

When are ALT and AST levels high

Answer 11

These are INTRACELLULAR aminotranferases. so they are normally low in the plasma. If elevated in the blood that means the cells containing them (often liver cells) are lysing.

Question 12

What happens in oxidative deamination?

Answer 12

The amino group is liberated as free ammonia. This primarily occurs on glutamate because this is the prodcut of transmaination. Glutamate is converted to NH3 and alpha-ketoglutate by glutamate dehydorgenase

**This NH3 is what enters the urea cycle. **

Question 13

When is glutamate DH active?

Answer 13

Generally after a protein rich meal and you’re breaking down AA forming glutamate and then liberating the NH3 through glutamate DH.

Can also be active during low blood glucose because is is making alpha-ketoglutarate which is a way to enter the TCA cycle and get energy.

Question 14

two places we get glutamate from

Answer 14

From the deamination of glutamine

from the amination of alpha-ketoglutarate.

Question 15

What to glutamate and glutamine become when they donate their NH3 group ? Dicuss the enzymes

Answer 15

When glutamate donates its
amino group, it donates the side chain amino group and is converted to α- ketoglutaric acid. When glutamine donates an amino group it is converted into
glutamate.

Glutamine –Glutaminase (removing NH3)–> Glutamate

Glutmate— Glutamine synthetase (adding NH3)–> Glutamine

Question 16

What AA are derived from the TCA cycle

Answer 16

Asparate Asparagine

Glutamate Glutamine

Question 17

Which AA are derived from intermediates of glycoclysis

Answer 17

Glycine ALanine Serine

Cystine

GAS C

Question 18

What happens to the products of cataboliem of AA

Answer 18

1. A portion of the free ammonia is excreted in the urine, but most is used in the synthesis of urea (most important route for disposal of nitrogen from the body).
2. The carbon skeletons of the α-keto acids are converted to common intermediates of the energy-producing, metabolic pathways as seen below.
3. The resulting intermediates can be metabolized to CO2 and water, glucose, fatty acids, or ketone bodies.

Question 19

When do we use AA for energy

Answer 19

When carbs are lacking in diet (or when we can’t use them like in diabetes) we convert the AA to OAA or pyruvate for glucose or glycogen.

Hormones like cortisone and cortisol from the adrenal cortex stimulate the sytnhesis of glucose from AA in the liver and is an antagonist to insulin

Question 20

Describe Maple Syrup Urine Disease

Answer 20

There are AA (I LIV) isoleucine, leucine and valine (all branched) that are used to maintain muscle mass in times of stress. Normally they are broken down by alpha-ketoDH bu twhen that enzyme is missing the urine is sweet smelling.

Babies cna seem normal at birth but the neuroligcal effects oft his are great. Can be monitored and prevented by dietrary restrictions.

Question 21

Importance of Methionin

What vitamins does it need

Answer 21

Its a sulfur containing AA and precurosor for sulfur AA

Acts as a lipotropic factor and mobolizes fat through liver to acoid accumulation

REQUIRED FOR THE SYNTHESIS OF CREATINE

When an ATP is transfer to the sulfur of methione is becomes SAM which is an important meethylating agent and contributes to the synthesis of brain NT and deox reactions.

it requires folic acid (b9) and B12 and without the vitamins it’ll cause an elevated homocystein level which can increae risk of coronary artery disease

Question 22

Explain homocystinuria

Answer 22

This is a build up of methionine or homocystine usually due to missing defect in the CBS cystathinoin B synthase.

CBS is the enzyme that converts homocystne to cystathinne.

This can lead to discolation of the lens, intellecutla disabilites and skeletal and neutolofical abnormaliles.

Question 23

Explain PKU

Answer 23

Phenklketonuria is a autosomal recessive disorder where we are missing PAH- phenylalanine DH. Thisis the enzyme that convert phenylaline to tyrosine in the liver.

IF PKU is untreated it can lead to CNS probels, seizures.

Controlable by diets low in phenylyaline and high in tyrosine.

Tyrosine is a precurosro to DOPA-DOPAMINE- NE- EPI

NE–EPi uses SAM which is the product of adding an ATP to the sulfur in methionine.

Question 24

What is alkaptouria?

Answer 24

This is black urine disease where urine is black when exposed to air due to a genetic disorder in the metabolism of phenylaline and tyrosine becuase they are missing the enzyme homogentisate oxygenase which degrades tyrosine.

Since we can’t degrade tyrosine we get homogentistic acid which is a byprodcut that accumulates and is excreted in the urine. THis can cause progressive arithristis and may not be noticed until 4 decades.

Albinism/vitiligo is another disorder when we can’t break tyrosine to melanin

Question 25

Importance of glutamine

Answer 25

Glutamine is essetnial to make glutamate and is abudant in bone, mucle and blood.

Preferred AA of the brain and invovled in NT biochem and ESSENTIAL IN TIMES OF STRESS

Question 26

Why is histidie important

Answer 26

It’s a precursor to histamine which is released by mast cells of mucus membrane during allergic reacion and by the CNS system during a mirgraine

Question 27

IMportance of Glycine

Answer 27

It mostly in small portions except in collagen where it’s 1/3 of the product.

Question 28

Importance of aspartate

Answer 28

This is where the NH3 comes for urea syntheiss

Question 29

IMportance of Trypotophan

Answer 29

It’s essential and about 50% of the precsuor for the body’s pyridine nucleotides. the rest come diet.

Also a precuros for B3 and when it is deficient we get Pellagra- which is shown by diarhhea, dementia and dermatitis.

serotonin and melatonin are trypotaphan deriviative

Serotonin- NT in the brain that regulates GI movemnet and contration of SM in arterioles and bronchioles.. can be converted to maeltonin

Question 30

Why is ammonia toxic

Answer 30

Becuase hwne in high amoutns it convertes the rxn towards glutamate so reducing the amount of alpha-ketoglutarate which is a TCA intermediate so less energy is prodcued.

Question 31

When would we have positive and negative nitrogen balance

Answer 31

POstiive- growth, pregnancy, recovering from illness

Negative- trauma burn, elderly, sureggery

normal adult is normal in balance

Question 32

Where do the nitrogen of the urea come from

Answer 32

1. One comes from oxidative demaination of glutamate (this is the free one in te first step)
2. One comes Asparatate

C- comes from bicarb

Question 33

POint of urea cycle

Answer 33

to make urea CO(NH2)2 from toxic ammonia NH3

I tonly takes place in the liver

Question 34

What is the carrier of carbon and mitrogen in the cycle? What happens to it at the end

Answer 34

Ornithine carries crbon and nitrogen and is present before and after the cycle.

Question 35

What are the two mitochondrial steps of urea cycle

Answer 35

1. NH3 + CO2—- CPS I—> carbonmoyl phosphate
2. Carbonyl phosphate + prithine— Ornithine transcarboylase(OTC)—> Citruline

Citruline can just move to the cytosol for te rest of the reaction

Question 36

What are the 3 cytoslic steps of urea

Answer 36

Citruline + asparate (the second nitrogen) COST ONE ATP — Arginosuccinate (ASS)—> Argininosuccinate

Arginnosuccinate—- Argininosuccinate lyase (ASL)—> fumarate (can do to TCA) and argiine

Arginine— ARG 1 (Arginase)—> ornithine (back to mitochondria) + Urea

Question 37

What steps in urea cost ATP

Answer 37

The first step with CPS I cost 2 ATP- activation

Adding asparate to L-citruline cost 1 ATP

Question 38

What steps are regulated in the urea cycle

Answer 38

CPS-1 is the rate limiting step

Is upregulated by N-acetyl glutamate which is an allosteric activator. The activator is formed from Acetyl CoA and glutamate. The enzyme that makes N-actyl glutamate is regulated by argiine

Long term regulaton- is high protein diet for about 4 days.

Question 39

HOw is urea excreted?

Answer 39

About 90% is excreted in the urine. A bit diffuses to the blood and enters GI tract where it is cleaved by bacterial urease into NH3 and CO2 and goes back to the urea cycle .

Question 40

IS the urea cycle reversible

Answer 40

Generally No, BUt can be with a large deltaG

Question 41

Connection between TCA and urea

Answer 41

One of the nitrogens for the urea cyucle comes from asparate which is derived from OAA a TCA intermediate.

Question 42

Function of BUN

Answer 42

BUN is blood urea nitrogen- this is generrally stable adn meaures the kidneys ability to excrete nitrogenous waste. Elevated BUN can mean renal failure, CHF so low BP and low filtration and UT obstructions

Question 43

What happens during cirrhosis of the liver to urea cycle

Answer 43

Cirrhosis interferes with the enzyme CPS I which is used to make carbomnyl which is the first step of the urea cycle

Question 44

What is hartups disease

Answer 44

Defect in intestinal absorption and renal absorption of neutral AA especially trypothpahn which is a precuros to serotonin, melanin, and B3–pellagra

Question 45

Cystinuria

Answer 45

AA when degraded need to actively be transported. One transport system COAL is used for cystine, ornithin, argiine, and lysine and cystinuria is a disorder of the proximal tubules reasborption of filtered cystine and dibasic AA. This genetic disorder can leads to percipitation of cystine and cause kidney stones and blocks the urinary tract. Oral hydration is important in these patient.