Biochemistry: Amino Group Metabolism, Heme Metabolism
What are the inputs and outputs from the amino acid pool?
--Inputs: diet, stomach digestion, pepsinogen, pancreatic enzymes, intestinal processing, absorption, turnover of endogenous proteins
--Outputs: excretion, protein building in fed state, aa catabolism during a fast
What are the steps of gastointestinal processing of proteins? Eat food. Stomach secretes hydrochloric acid (HCl) and intrinsic factor (IF) from parietal cells and pepsinogen from chief cells. Pepsinogen is activated to pepsin by HCl and then pepsin catalyzes its own activation. Chyme leaves stomach through the pyloric sphincter and enters the duodenum where it is doused with bile and pancreatic enzymes. Bicarbonate neutralizes the acid and enteropeptidase from the pancreas starts the proenzyme activation cascade by converting trypsinogen to trypsin. Trypsin then catalazes conversions to make chymotrypsin, elastase and carboxypeptidases which go to work chopping up proteins in the brush border. Amino acids are absorbed as di- and tri-peptides, into intestinal brush border cells via cotransport with sodium (driven by low intracellular sodium). The gamma-glutamyl cycle is another transport mechanism for aa's. There are disorders of aa transport including: cystinuria and Hartnup's disease. Once in the blood stream the aa's go where???
What are the principle nitrogen-containing urinary waste products? (among vertebrates)
1)Ammonia - Due to the high solubility of ammonia in water and its small molecular size, ammonia readily diffuses to the aquatic environment at gill or skin surface. Only a small portion is excreted by the kidney.
2)Urea - In humans carries ~85% of N excreted. Ureotelic organisms convert ammonia to urea in liver (2N:1C ratio). Energetically more expensive to produce urea, but it is soluble in water and has a low toxicity so it can be tolerated at higher levels than ammonia and excreted as liquid urine. High urea concentration in urine cuts down on excretory water loss.
3)Uric Acid - Uricotelic organisms convert ammonia to uric acid (4N:5C). Energetically the most expensive to produce, low toxicity and only slightly soluble in water. Removal of water from urine causes uric acid to precipitate, so it is excreted as a semisolid paste with little water loss. Some insects deposit uric acid within body (e.g., fat body) so that no water is lost via excretion.
4) Others: creatine, creatinine, guanidine, choline, carnitine, piperidine, spermidine, dopamine, epinephrine, norepinephrine, serotonin, tryptamine, levulinique amino-acid, bilirubin, and so on.
What is meant by "nitrogen balance"?
input - output = zero, normally
Positive nitrogen balance: childhood, building muscle
Negative nitrogen balance: fasting, wasting away
What are the essential amino acids?
PVT TIM HALL
phenylalanine
valine
tryptophan
threonine
isoleucine
methionine
histidine
arginine
leucine
lysine
When is arginine an essential amino acid? When not enough of it is produced in the urea cycle to serve the body's needs. Argininosuccinate is split into fumarate and arginine. Fumarate goes into the Krebs cycle and arginine looses urea becoming ornithine, gaining ammonia and carbon dioxide to become citrulline, gaining aspartate to become argininosuccinate, and the cycle goes round again.
What are the three phases of aa degradation? Transamination, deamination, and urea formation.
What is transamination? Transamination (or aminotransfer) is the reaction between an amino acid and an alpha-keto acid. The amino group is transferred from the aa to the keto-acid; this results in the amino acid being converted to the corresponding α-keto acid, while the reactant α-keto acid is converted to the corresponding amino acid (if the amino group is removed from an amino acid, an α-keto acid is left behind). The human body synthesizes the 10 non-essential amino acids and transamination is the process by which most of these syntheses occur. The chirality of an amino acid is determined during transamination. This reaction uses the coenzyme PLP, and is considered to be a kinetically perfect reaction. The product of transamination reactions depend on the availability of alpha-keto acids. The products usually are either alanine, aspartate or glutamate, since their corresponding alpha-keto acids are produced through metabolism of fuels.
Illustrate transamination using an alpha-amino acid and alpha-ketoglutarate. Which cellular compartment does transamination happen in? Which aa's undergo transamination? Let's see....transamination is moving an amine group around from one molecule to another. Alpha KG plus an aa and the products are alpha-keto acids and Glutamate. Enzymes = aminotransferases aka transaminases. Cofactor: pyridoxal phosphate (vitamine B6 derivative aka "active" B6--is phosphorylated).
WHAT CELLULAR COMPARTMENT? In liver and muscle, cytoplasm I think.
WHICH AA'S CAN DO THIS? Glutamate is primary but all aa's EXCEPT Ser, Thr and His can undergo transamination.
When blood sugar is low animals metabolize proteins to amino acids at the expense of muscle tissue. The preference of liver transaminases for oxaloacetate or alpha-ketoglutarate plays a key role in funneling nitrogen from amino acid metabolism to Asp and Glu for conversion to urea for excretion of nitrogen. Similarly, in muscles the use of pyruvate for transamination gives Ala, which is carried by the bloodstream to the liver. Here other transaminases regenerate pyruvate, which provides a valuable precursor for gluconeogenesis. This alanine cycle is analogous to the Cori cycle which allows anaerobic metabolism by muscles.
What is an alpha-aa? An alpha amino acid has the amino, carboxylate group, and side chain (R group) all attached to the α-carbon. The side chains can vary in size from just a hydrogen atom in glycine through a methyl group in alanine to a large heterocyclic group in tryptophan.
OK, so Glutamate (in the notes) is converted to alpha-KG while active B6 is converted to pyridoxamine phosphate---the vitamin B gets an extra NH2 that was taken off the Glutatmate....then the pyridoxamine phosphate is converted back to pyridoxal phosphate (active B6) by giving that spare amine group to an oxaloacetate (OAA) changing it to aspartate. HUH?
What unique functions are performed by alanine and glutamine in aa metabolism?
ALANINE
--can get into the liver
--can be made to pyruvate --> GLUCOSE
--in muscles the use of pyruvate for transamination gives Ala, which is carried by the bloodstream to the liver. Here other transaminases regenerate pyruvate, which provides a valuable precursor for gluconeogenesis. This alanine cycle is analogous to the Cori cycle which allows anaerobic metabolism by muscles.
GLUTAMINE (glutamate)
--leads to Asp prioduction and N excretion as urea
--liver transaminases prefer oxaloacetate or alpha-ketoglutarate funneling nitrogen from amino acid metabolism to Asp and Glu for conversion to urea for excretion
Why are levels of glutamate and glutamine elevated in the aa pool? Because they're useful intermediates made via aminotransferases from other aa's, can facilitate nitrogen excretion.
Which organs play a central role in amino group metabolism? gut (absorbtion), liver, muscle, kidney & other cells.
Pyridoxal is designated as which vitamin? active B6
What role is played by pyridoxal phosphate in transamination reactions? it holds the amine group in between aa's
What are the functions of the glucose-alanine cycle? using muscle lactate byproduct???, recycle carbon skeletons between muscle and liver, transport NH4+ to the liver -->converted to urea. Wiki: The alanine cycle is quite similar to the Cori cycle. When muscles produce lactate during times of decreased oxygen, they also produce alanine. This alanine is shuttled to the liver where it is used to make glucose. This process is less productive than the Cori Cycle, which uses lactate, since a byproduct of energy production from alanine is production of urea. Removal of the urea is energy-dependent, thus the net ATP produced is less than that found in the Cori Cycle.
What tissues are involved in this cycle? muscles, liver
--Inputs: diet, stomach digestion, pepsinogen, pancreatic enzymes, intestinal processing, absorption, turnover of endogenous proteins
--Outputs: excretion, protein building in fed state, aa catabolism during a fast
What are the steps of gastointestinal processing of proteins? Eat food. Stomach secretes hydrochloric acid (HCl) and intrinsic factor (IF) from parietal cells and pepsinogen from chief cells. Pepsinogen is activated to pepsin by HCl and then pepsin catalyzes its own activation. Chyme leaves stomach through the pyloric sphincter and enters the duodenum where it is doused with bile and pancreatic enzymes. Bicarbonate neutralizes the acid and enteropeptidase from the pancreas starts the proenzyme activation cascade by converting trypsinogen to trypsin. Trypsin then catalazes conversions to make chymotrypsin, elastase and carboxypeptidases which go to work chopping up proteins in the brush border. Amino acids are absorbed as di- and tri-peptides, into intestinal brush border cells via cotransport with sodium (driven by low intracellular sodium). The gamma-glutamyl cycle is another transport mechanism for aa's. There are disorders of aa transport including: cystinuria and Hartnup's disease. Once in the blood stream the aa's go where???
What are the principle nitrogen-containing urinary waste products? (among vertebrates)
1)Ammonia - Due to the high solubility of ammonia in water and its small molecular size, ammonia readily diffuses to the aquatic environment at gill or skin surface. Only a small portion is excreted by the kidney.
2)Urea - In humans carries ~85% of N excreted. Ureotelic organisms convert ammonia to urea in liver (2N:1C ratio). Energetically more expensive to produce urea, but it is soluble in water and has a low toxicity so it can be tolerated at higher levels than ammonia and excreted as liquid urine. High urea concentration in urine cuts down on excretory water loss.
3)Uric Acid - Uricotelic organisms convert ammonia to uric acid (4N:5C). Energetically the most expensive to produce, low toxicity and only slightly soluble in water. Removal of water from urine causes uric acid to precipitate, so it is excreted as a semisolid paste with little water loss. Some insects deposit uric acid within body (e.g., fat body) so that no water is lost via excretion.
4) Others: creatine, creatinine, guanidine, choline, carnitine, piperidine, spermidine, dopamine, epinephrine, norepinephrine, serotonin, tryptamine, levulinique amino-acid, bilirubin, and so on.
What is meant by "nitrogen balance"?
input - output = zero, normally
Positive nitrogen balance: childhood, building muscle
Negative nitrogen balance: fasting, wasting away
What are the essential amino acids?
PVT TIM HALL
phenylalanine
valine
tryptophan
threonine
isoleucine
methionine
histidine
arginine
leucine
lysine
When is arginine an essential amino acid? When not enough of it is produced in the urea cycle to serve the body's needs. Argininosuccinate is split into fumarate and arginine. Fumarate goes into the Krebs cycle and arginine looses urea becoming ornithine, gaining ammonia and carbon dioxide to become citrulline, gaining aspartate to become argininosuccinate, and the cycle goes round again.
What are the three phases of aa degradation? Transamination, deamination, and urea formation.
What is transamination? Transamination (or aminotransfer) is the reaction between an amino acid and an alpha-keto acid. The amino group is transferred from the aa to the keto-acid; this results in the amino acid being converted to the corresponding α-keto acid, while the reactant α-keto acid is converted to the corresponding amino acid (if the amino group is removed from an amino acid, an α-keto acid is left behind). The human body synthesizes the 10 non-essential amino acids and transamination is the process by which most of these syntheses occur. The chirality of an amino acid is determined during transamination. This reaction uses the coenzyme PLP, and is considered to be a kinetically perfect reaction. The product of transamination reactions depend on the availability of alpha-keto acids. The products usually are either alanine, aspartate or glutamate, since their corresponding alpha-keto acids are produced through metabolism of fuels.
Illustrate transamination using an alpha-amino acid and alpha-ketoglutarate. Which cellular compartment does transamination happen in? Which aa's undergo transamination? Let's see....transamination is moving an amine group around from one molecule to another. Alpha KG plus an aa and the products are alpha-keto acids and Glutamate. Enzymes = aminotransferases aka transaminases. Cofactor: pyridoxal phosphate (vitamine B6 derivative aka "active" B6--is phosphorylated).
WHAT CELLULAR COMPARTMENT? In liver and muscle, cytoplasm I think.
WHICH AA'S CAN DO THIS? Glutamate is primary but all aa's EXCEPT Ser, Thr and His can undergo transamination.
When blood sugar is low animals metabolize proteins to amino acids at the expense of muscle tissue. The preference of liver transaminases for oxaloacetate or alpha-ketoglutarate plays a key role in funneling nitrogen from amino acid metabolism to Asp and Glu for conversion to urea for excretion of nitrogen. Similarly, in muscles the use of pyruvate for transamination gives Ala, which is carried by the bloodstream to the liver. Here other transaminases regenerate pyruvate, which provides a valuable precursor for gluconeogenesis. This alanine cycle is analogous to the Cori cycle which allows anaerobic metabolism by muscles.
What is an alpha-aa? An alpha amino acid has the amino, carboxylate group, and side chain (R group) all attached to the α-carbon. The side chains can vary in size from just a hydrogen atom in glycine through a methyl group in alanine to a large heterocyclic group in tryptophan.
OK, so Glutamate (in the notes) is converted to alpha-KG while active B6 is converted to pyridoxamine phosphate---the vitamin B gets an extra NH2 that was taken off the Glutatmate....then the pyridoxamine phosphate is converted back to pyridoxal phosphate (active B6) by giving that spare amine group to an oxaloacetate (OAA) changing it to aspartate. HUH?
What unique functions are performed by alanine and glutamine in aa metabolism?
ALANINE
--can get into the liver
--can be made to pyruvate --> GLUCOSE
--in muscles the use of pyruvate for transamination gives Ala, which is carried by the bloodstream to the liver. Here other transaminases regenerate pyruvate, which provides a valuable precursor for gluconeogenesis. This alanine cycle is analogous to the Cori cycle which allows anaerobic metabolism by muscles.
GLUTAMINE (glutamate)
--leads to Asp prioduction and N excretion as urea
--liver transaminases prefer oxaloacetate or alpha-ketoglutarate funneling nitrogen from amino acid metabolism to Asp and Glu for conversion to urea for excretion
Why are levels of glutamate and glutamine elevated in the aa pool? Because they're useful intermediates made via aminotransferases from other aa's, can facilitate nitrogen excretion.
Which organs play a central role in amino group metabolism? gut (absorbtion), liver, muscle, kidney & other cells.
Pyridoxal is designated as which vitamin? active B6
What role is played by pyridoxal phosphate in transamination reactions? it holds the amine group in between aa's
What are the functions of the glucose-alanine cycle? using muscle lactate byproduct???, recycle carbon skeletons between muscle and liver, transport NH4+ to the liver -->converted to urea. Wiki: The alanine cycle is quite similar to the Cori cycle. When muscles produce lactate during times of decreased oxygen, they also produce alanine. This alanine is shuttled to the liver where it is used to make glucose. This process is less productive than the Cori Cycle, which uses lactate, since a byproduct of energy production from alanine is production of urea. Removal of the urea is energy-dependent, thus the net ATP produced is less than that found in the Cori Cycle.
What tissues are involved in this cycle? muscles, liver