生技大二學(xué)習(xí)生化上冊aminoacid1.student

1、# 1 Amino Acid Metabolism1. General FeaturesNitrogen Balance & Metabolic Pools2. DegradationTransamination & Glutamate Dehydrogenases3. Urea Cycle4. Sulfur-containing amino acids5. Creatine & CreatinineObjectivesOutline the general features of the amino acid (AA) pool & how these relate to positive

2、& negative N balance.Essential vs non-essential AAsInterorgan transport and utilization of glutamine and alanineN balance = Nin - NoutMajor dietary source of N is Protein (95%), since the diet has very few free amino acidsAA are used for Protein Synthesis & N containing compounds 3 AA in excess are

3、degraded (used for energy)N is disposed of in urea (80%), ammonia, uric acid or creatinine in urine with small amounts in fecal matter (undigested)Positive Nitrogen BalanceNegative Nitrogen Balance1. Stress2. Decreased Intake3. Lack of an essential AASpecificity of Some Proteolytic EnzymesVery few A

4、A are present in the free form in the diet. Most are absorbed following digestion as AA + peptides (important in transport deficiencies).Various enzymes cleave different bonds.Sterospecific Transport Systems for Amino AcidsUptake (transport) systems exist especially in intestine & kidney. Lack of sp

5、ecific transporter results in a disease state.This can be partially e through uptake of peptides.Metabolic Pool of Amino Acids Metabolic pool AA has no storage form in mammals (as with other life forms) as free AA or as specialized storage form (such as glycogen for glucose, TG for FA) but a certain

6、 percentage of muscle & structural proteins are “expendable”.AA are used for proteins, N compounds, energy (also via glucose) but increased protein breakdown will eventually compromise normal protein function.Therefore need a small mobile pool of free AA in cells and bloodPool size is regulated (no

7、more than 50% changes) Pool size is small relative to flux16g in = 16g out : Nequilibrium AA = 30g 300g cell proteinMetabolic Pool of Amino AcidsThe three major draws on the amino acid pool are:AA Proteins (not covered here)AA Catabolism (NH4+ discarded, glutamine used)AA N containing compoundsas -

8、whole/part AA integratedor - only the amino (N) group is usedAA catabolized, then NH4+ incorporated into glutamine This synthesis is not compromised even when dietary P is decreased because they are essential for cellular function.Major Functions of Amino Acids Derived from Dietary ProteinOxidationG

9、lycogenic amino acids: -Blood glucose-EnergyKetogenic amino acids: -Acetyl CoA-Stored fat-EnergyBiosynthesis of nitrogen-containing metabolitesHemeBlood cellCholinePLGlycosamineSugarNucleotidesDNAProtein synthesisProteinBiogenic aminesNeurotransmittersCarnitineHeartCreatine phosphateEnergy Maintenan

10、ce of Pool SizeSurplus AA to biosynthetic requirements are degradedAA oxidation is the major mechanism of degradation Rate Oxidation Pool Sizeand relates to enzyme induction.Balanced composition of AA pool is important to meet all cell requirements for all AASummary of Protein Metabolisma) keto acid

11、s are funneled into the Krebs cycle (glucogenic/ketogenic)b) NH4+ is cleared via urea, NH4+, with uric acid however major product is urea (80%)c) Creatine/creatinine important for energy consideration Essential & Non-essential AA1.EAA : Humans (mammals) cannot synthesize their carbon skeletons de no

12、vo. Some EAA are considered essential because we cannot synthesize enough, especially for growth (children).2. NEAA: Synthesized from intermediates of glucose/TCA cycle except TYR (cannot make aromatic ring).3.The grouping of E vs NE was determined experimentally by feeding diets lacking in a single

13、 AA and measuring Nin/Nout. . If balance negative then = EAAEssential & Non-essential AA1.The difference between EAA & vitamins that is AA are needed in substrate amounts to make proteins and nitrogen compounds. Vitamins are needed in catalytic amounts (co-factors for enzymes) and therefore can be r

14、eused.2. All AA must be provided simultaneously (not hours after).3. Normally: no “disease” can be attributed to deficiency in a single AA except Pellagra which is due to a lack of niacin nicotinate a component of NADTRP nicotinate NADCorn P is deficient in TRP therefore corn diet pellagra. Preparat

15、ion is important: Because TRP necessary to make niacinCorn + Alkali absorption of nicotinate present in corn niacinEssential & Non-essential AA Conditionally essential(i) ARG:can be made, but not enough(ii) HIS: controversial (essential for growth in children)(iii) PHE essential, TYR can be made fro

16、m PHE but when enzyme is missing (phenyl- ketonuria) then PHE TYR; Therefore TYR is essential(iv) MET CYS; Similarly, if MET CYS then CYS essential Even with excess, important in excretion NH4+ therefore continue to be madeGlycogenic and KetogenicAmino Acids1.Glucogenic: converted to glucose via pyr

17、uvate2.Ketogenic: converted to ketone bodies 3.Some are both4.During fasting when FA are the major fuel FA cannot be converted to glucose therefore AA glucose & ketone bodies (especially for brain) -AA pyruvate liver glucose -keto AA + FA ketone bodies (acetoacetate & 3 hydroxybutyrate)Specialized A

18、mino Acid Roles1.Certain NEAA continue being synthesized even when adequate levels are supplied in diet because of a specialized role2.ARG urea synthesisASP urea synthesisGLU conduit for disposal of N3.ALA & GLN key role in exchange between tissues (liver & skeletal muscle)4.Liver: major site glucon

19、eogenesis (AA Glucose) major site urea synthesis (kidneys to a lesser extent) 5.Skeletal Muscle: 60% total body protein, 50% total body AA pool and is the major source to provide AA carbons hepatic gluconeogenesis AA are released from muscle during the post- absorptive state (O/N fast). Of the AA re

20、leased by muscle ALA= 30% & GLN= 25% (total 50%) But output (ALA+GLN) abundance in muscle proteins which contain 7-10% ALA & 6% GLNWhere does this ALA & GLN come from?Sources of Alanine (from Muscle)(i)Muscle: Protein ALA + AA AA NH4+ + keto acids keto acids ALA (“simplest” AA). Therefore total ALA

21、released ALA derived from proteins(ii) Liver: ALA NH4+ + keto acids NH4+ urea(iii) As well Glucose Pyruvate (no N) ALA (with N)Therefore ALA serves as a vehicle for transport of NH4+ from muscle to liver (NH4+ is generated through breakdown of AA energy).(iv) Because free NH4+ is very toxic even at

22、low levels therefore Pyruvate + NH4+ ALA (non-toxic)(v) In liver: NH4+ urea for excretion Sources of Glutamine (from Muscle) (i) Extra GLN released is also made from other AA & serves as a non-toxic transport of NH4+ from muscle kidneys & gut (previous fig)(ii) Kidneys: GLN ALA (to the Liver )& GLN

23、glucose (blood) +NH4+ (Urine)(iii) Gut: GLN ALA (to the liver) Response to Food Deprivation(i) For the first 7 days, maintain blood glucose (brain use 65% of glucose 400 - 600 Cal)(ii) 7 days: Protein proteolysis decreases (protect essential proteins) therefore use over a prolonged period compromise

24、s organism.(iii) Switch to Ketone bodiesCase # 1 Amino Acid Metabolism: General Features Case DiscussionA worker reported to a physician with many of the symptoms of pellagra: swollen tongue, dermatitis, and nervous disturbances. The mans diet consisted principally of sweet corn with a small amount of other sources of protein. The identical twin of the man had no similar complaints, and although the twins diet was high in sweet corn, it was mixed with significant amounts of beans. 3. Pel