SChmidt 3 lectures Flashcards
List the esstential AA
PVT TIM HALL
Phenylalanine
Valine
Threonine
Tryptophan
Isoleucine
Methionine
Histidine
Arginine***
Lysine
Leucine
Arigine is nonesstential but in periods of growth its essential.
Nonessential AA
AAACGGGPS
ALanine
Arginine
Aspartate
Cysteine
Glutamate
Glutamine
Glycine
Proline
Serine
AA that are JUST ketogenic
What does this mean?
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
Which AA are both Glucogenic and Ketogenic
Tyrosin, phenylalanine, tryptophan
Which AA are just glucogenic. Where do they enter the cycle? How are they used
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.
Functions of Amintransferases
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
Prodcudts of ALT and AST
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
Explain the alanine glucose cycle
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!
What is the cofactor for aminotransferases
Pyridoxal phosphate (functional form of B6)
When would you degrade AA? Sytnehsis?
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
When are ALT and AST levels high
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.
What happens in oxidative deamination?
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. **
When is glutamate DH active?
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.
two places we get glutamate from
From the deamination of glutamine
from the amination of alpha-ketoglutarate.
What to glutamate and glutamine become when they donate their NH3 group ? Dicuss the enzymes
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
What AA are derived from the TCA cycle
Asparate Asparagine
Glutamate Glutamine
Which AA are derived from intermediates of glycoclysis
Glycine ALanine Serine
Cystine
GAS C
What happens to the products of cataboliem of AA
- 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).
- The carbon skeletons of the α-keto acids are converted to common intermediates of the energy-producing, metabolic pathways as seen below.
- The resulting intermediates can be metabolized to CO2 and water, glucose, fatty acids, or ketone bodies.
When do we use AA for energy
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
Describe Maple Syrup Urine Disease
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.
Importance of Methionin
What vitamins does it need
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
Explain homocystinuria
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.
Explain PKU
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.
What is alkaptouria?
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
Importance of glutamine
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
Why is histidie important
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
IMportance of Glycine
It mostly in small portions except in collagen where it’s 1/3 of the product.
Importance of aspartate
This is where the NH3 comes for urea syntheiss
IMportance of Trypotophan
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
Why is ammonia toxic
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.
When would we have positive and negative nitrogen balance
POstiive- growth, pregnancy, recovering from illness
Negative- trauma burn, elderly, sureggery
normal adult is normal in balance
Where do the nitrogen of the urea come from
- One comes from oxidative demaination of glutamate (this is the free one in te first step)
- One comes Asparatate
C- comes from bicarb
POint of urea cycle
to make urea CO(NH2)2 from toxic ammonia NH3
I tonly takes place in the liver
What is the carrier of carbon and mitrogen in the cycle? What happens to it at the end
Ornithine carries crbon and nitrogen and is present before and after the cycle.
What are the two mitochondrial steps of urea cycle
- NH3 + CO2—- CPS I—> carbonmoyl phosphate
- Carbonyl phosphate + prithine— Ornithine transcarboylase(OTC)—> Citruline
Citruline can just move to the cytosol for te rest of the reaction
What are the 3 cytoslic steps of urea
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
What steps in urea cost ATP
The first step with CPS I cost 2 ATP- activation
Adding asparate to L-citruline cost 1 ATP
What steps are regulated in the urea cycle
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.
HOw is urea excreted?
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 .
IS the urea cycle reversible
Generally No, BUt can be with a large deltaG
Connection between TCA and urea
One of the nitrogens for the urea cyucle comes from asparate which is derived from OAA a TCA intermediate.
Function of BUN
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
What happens during cirrhosis of the liver to urea cycle
Cirrhosis interferes with the enzyme CPS I which is used to make carbomnyl which is the first step of the urea cycle
What is hartups disease
Defect in intestinal absorption and renal absorption of neutral AA especially trypothpahn which is a precuros to serotonin, melanin, and B3–pellagra
Cystinuria
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.
