Chapter 15 - Protein Catabolism

What are the steps of protein catabolism?

Digestion

Removal and disposal of amino groups

Degradation of keto acid carbon skeleton

Where does protein digestion occur?

Stomach and intestines

Where does removal and disposal of the amino group in protein catabolism occur?

Liver

What process involves removal and disposal of the amino group in protein catabolism?

Urea cycle

Where does degradation of keto acid carbon skeleton in protein catabolism occur?

Liver

What process is involved in degradation of the keto acid carbon skeleton in protein catabolism?

Citric acid cycle

Entry of food into the stomach stimulates the gastric mucosa to secrete what?

Gastrin

What does gastrin release stimulate the secretion of?

HCl from parietal cells

Pepsinogen from chief cells

What is the function of HCl in the stomach?

Denature protein’s 3D structure making the peptide bonds of the primary structure more accessible to enzymes

What is the function of pepsinogen from the chief cells?

Zymogen that will be converted to pepsin and cleave peptide bonds of aromatic amino acids

The acidic chyme released into the duodenum stimulates the secretion of what?

Secretin

What stimulates the exocrine pancreas to release digestive enzymes?

Cholecystokinin (CCK)

What are the digestive enzymes of the pancreas?

Trypsinogen

Chymotrypsinogen

Procarboxypeptidases

What activates both chymotrypsinogen and procarboxypeptidases?

Trypsinogen

What is the function of the pancreatic digestive enzymes?

Hydrolyze peptide bonds

What transporters help take amino acids through the intestinal epithelium?

Sodium-coupled transporters

What process involves the transfer of an amino acid to another molecule, typically alpha-ketoglutarate?

Transamination

What process involves the removal of an amino group which then combines with water to form ammonia?

Deamination

What is typically the product of deamination?

Ammonia - ammonium ions

What enzyme class is important for transamination?

Aminotransferase or transaminase

What enzyme class is key for deamination?

Deaminase

What coenzyme is important for transaminases?

Pyridoxal phosphate (PLP) and B6

In what two ways can the amino group from glutamate be removed in the liver cell?

1. Glutamate dehydrogenase takes the nitrogen off and makes carbamoyl phosphate

2. Aspartate aminotransferase transfers nitrogen from glutamate to oxaloacetate (which turns into aspartate)

What cycle does the carbamoyl phosphate and aspartate from amino group removal from glutamate enter?

Urea cycle

How does ammonia generated in non-muscle tissue get transported to the hepatocyte mitochondria?

Ammonia (amino group) combines with glutamate to make glutamine, which goes to liver mitochondria for two deaminations

What substrate is ALT specific for?

Alanine

What substrate is AST specific for?

Aspartate

What can be used as clinical indicators of liver disease?

Elevated levels of AST and ALT

What process does glutamate go through once it is transported to the hepatocyte mitochondria?

Oxidative deamination

What enzyme catalyzes the amino group liberated as ammonia and alpha-ketoglutarate regeneration?

Glutamate dehydrogenase

What are the coenzymes for glutamate dehydrogenase?

NAD+ or NADP+

T/F: Ammonia can cross the blood-brain barrier.

True

What is the glucose alanine cycle?

Amino groups transferred to alpha-ketoglutarate to make glutamate, then transferred to pyruvate to alanine, which is sent to the liver where the amino group is transferred to alpha-ketoglutarate to make glutamate. This enters the liver mitochondria for deamination. The alanine loses the amino group and becomes pyruvate, which can be used for gluconeogenesis.

What happens to alanine when the amino group is removed?

becomes pyruvate

What is the purpose of the urea cycle?

Make neurotoxic ammonia water-soluble for excretion

Where does the urea cycle occur?

Mitochondria AND cytosol of hepatocyte

What is the rate-limiting enzyme of the urea cycle?

Carbamoyl phosphate synthetase I (CPS I)

How are the the Urea and Krebs cycles linked?

Urea intermediates replenish Krebs intermediates and vice versa

Why are the Urea Cycle and Krebs cycle mixed?

Metabolism of the amino acid carbon skeletons and amino groups simultaneously

What is the name of the link between the Urea Cycle and Krebs cycle?

Aspartate-arginosuccinate shunt

What 6 amino acids can skeletal muscle oxidize?

LIV GAA

Leucine, isoleucine, valine, glutamate, aspartate, asparagine

What molecules link the Krebs and Urea cycles?

Oxaloacetate from Krebs converts to aspartate, which enters Urea Cycle and makes arginosuccinate, which makes arginine and fumarate. Fumarate can then enter Krebs to regenerate oxaloacetate

Once entered into Krebs, what can fumarate regenerate?

Oxaloacetate

What happens to urea after it’s produced?

Excreted by kidney

What does blood ammonia levels test for?

Liver function

What does blood urea nitrogen test for?

Kidney function

What coenzymes are required for the prep step of the urea cycle?

CO₂ and 2 ATP

In what pathway is CPS II used?

Pyrimidine synthesis

Where does the rate-limiting step of the urea cycle occur?

Mitochondrial matrix