Protein metabolism in exercise (wk7)

Question 1

How we process dietary proteins in the body
-What are proteins

Answer 1

-What are proteins? -> Proteins are made up of amino acids (AA). There are 20 amino acids, of which 9 are essential amino acids (EAA).

Question 2

Processing of dietary proteins: stomach

Answer 2

• After the ingestion of protein, digestion begins in the stomach
• In the stomach, food is mixed with gastric juices due to the activity of the smooth muscle in the stomach wall
• In response to the ingestion of food the stomach secretes the hormone gastrin
• Gastrin in turn stimulates the secretion of hydrochloric acid (HCI) and pepsinogen
• HCI and Pepsinogen are key components of the gastric juices needed for protein breakdown
• HCI is secreted via the gastric glands. It causes the stomach to reach a pH of 1.5-3.5 (HCI -> H+ + CI-). The low pH denatures proteins.
• Pepsinogen is also secreted via the gastric glands and generates pepsin
• Pepsin must be converted from pepsinogen to be effective which happens when pesinogen encounters the gastric juices and unfolds
• Pepsin is maximally effective at a pH between 1-2
• Pepsin catalyses the hydrolysis of peptide bonds

Question 3

Processing of dietary proteins: Small intestine

Answer 3

• After the stomach contents pass into the duodenum, their acidic pH cause the secretion of bicarbonate (HCO3-) into the intestinal lumen
• In turn, this causes the secretion of the hormone secretin into circulation
• Secretin causes the pancreas to release more (HCO3-) into the intestinal lumen via the pancreatic duct
• Neutralization protects the intestinal wall from high acid stomach acids
• The pancreas cells release pancreatic enzymes as inactive precursors called zymogens, or the generators of enzymes
• The synthesis of inactive enzymes protect against the degradation of its own proteins
• Cholecystokinin, is the hormone which triggers the secretion of pancreatic zymogenes to the duodenum

Question 4

Describe the protein content of the human body

Answer 4

-Proteins are present in every cell in the body, as well as extracellular fluids (interstitial fluid and plasma) and solids (connective tissue)
-Men = 16% total protein / Women = 14% total protein
-Differences are due to body composition, and women in particular having a larger amount of adipose tissue which is low in protein and high in triglycerides. E.g. ~75kg male has ~12kg of protein

Question 5

Compare how different exercise types affect protein turnover in muscle
+draw the diagram

Answer 5

-Protein turnover -> Protein in the human body exist in a constant state of muscle protein synthesis and breakdown

Question 6

Describe the effects of exercise on protein turnover

Answer 6

• In a fasted state muscle protein breakdown exceeds protein synthesis = negative net balance
• Following exercise, both protein synthesis and breakdown increase. However, a negative net balance is still apparent
• In a fed state (post exercise) following protein feeding, protein synthesis far exceeds protein breakdown, and a positive protein balance is created
• This differs slightly depending on type of exercise, population, and training status

Question 7

Describe the effects of resistance on protein turnover

Answer 7

• When combined with sufficient protein intake, resistance exercise (RE) can contribute to an increase in cross-sectional area of muscle fibres known as muscle hypertrophy and an increase in muscle strength
• Daily rates of hypertrophy are ~0.1-0.2% until a plateau is reached that is ~33% above baseline levels. However, an individual rates of hypertrophy can exceed 50% of baseline
• A number of factors influence muscle adaptations to resistance exercise including training: volume/ intensity and frequency

Question 8

Effects of endurance exercise on protein turnover

Answer 8

• Endurance exercise does not commonly contribute to muscle hypertrophy
• Common adaptations to endurance training include
  1. Increases in mitochondrial content
  2. Mitochondrial biogenesis (i.e. an increase in new mitochondria)
  3. Mitochondrial hypertrophy (i.e. an enlargement of mitochondria)
• These adaptations allow for the muscle to generate a larger amount of ATP through the aerobic breakdown of carbohydrates, lipids and protein. This is a more economical source of energy.

Question 9

Describe amino acid degradation and synthesis

Answer 9

-Amino acids are not just a building block for muscle hypertrophy. They are also used as an energy source.
-Each individual AA follows an individualised catabolic route, the catabolic process of all AA involve the removal of the a(alpha)-amino acid group.
-After the disposal od the a(alpha)-amino groups, the carbon skeleton of the AA’s lead to intermediate compounds of carbohydrate and lipid metabolism
-The AA’s can be catabolised aerobically to produce CO2 and ATP

Question 10

Describe deamination

Answer 10

• Serine, threonine and glutamine discard of their amino groups via deamination
• This reaction forms a(alpha)-keto acids and ammonium
• Ammonium is highly toxic
• Ammonia is converted into urea into the liver, and it is excreted by the kidneys
• Both urea can ammonia can be excreted in urine and sweat

Question 11

Describe transamination

Answer 11

• The transfer of one amino group from one molecule to another. This reaction is catalysed via an enzyme called aminotransferase.
• -The most usual and major keto acid involved with transamination reactions is alpha-ketoglutarate, an intermediate in the citric acid cycle
• Transamination process is reversible

Question 12

What can alpha-keto acid be converted to (4)

Answer 12

• Pyruvate
• Acetyl-CoA
• Acetoacetyl CoA
• Succinyl CoA, Fumarate, Oxaloacetate (components of the Citric Acid Cycle)

Question 13

Glutamate disposes of its alpha-amino group by:

Answer 13

• Oxidative deamination
• These reactions are catalysed by glutamate dehydrogenase (an enzyme in the mitochondrial matrix)
• The term oxidative deamination is used as glutamate, loses its amino group and is oxidised by NAD+ or NADP+
• These reactions both generate ammonium and a(alpha)-ketoglutarate which can also enter the Citric Acid Cycle

Question 14

How do you prevent ammonium build up

Answer 14

• Glutamine -> The enzyme glutamine synthetase catalyses the conversion of glutamate to glutamine, using ATP. Glutamine then travels to the liver for processing.
• Alanine -> Alanine is produced when pyruvate receives the amino acid group of glutamine. This reaction is catalysed by alanine aminotransferase. A(alpha)-ketoglutarate is also formed.

Question 15

What is amino acid synthesis

Answer 15

• Our bodies can synthesize amino acids
• However, we do not have the capacity to synthesise 9 of the 20 amino acids
• These are our EAA’s
• NEAA’s are AA’s which we can synthesize
• Therefore, we need t ingest EAA’s as part of our diet

Question 16

Describe the influence on amino acid metabolism
-Muscle

Answer 16

• In active fibres, AA degradation is favoured (via glutamate dehydrogenase)
• This reaction is inhibited by ATP/GTP and activated by ADP/GDP. Therefore, during exercise (i.e. a state of energy depletion) glutamate deamination occurs.
• This produces a(alpha)-ketoglutarate, allowing for potential AA oxidation
• However, only he oxidation of branched chain amino acids (BCAA); leucine, isolelucine and valine increase with exercise
• The liver lacks the aminotransferase required to convert BCAA into a(alpha)-keto acids, increasing BCAA content in the skeletal muscle
• A(alpha)-ketoisocaproate is often measured to measure BCAA catabolism
• Branched chain a(alpha)-keto acids are next decarboxylated by the branched chain a(alpha)-keto acid dehydrogenase complex

Question 17

Describe the effect of exercise on amino acid metabolism
-Liver

Answer 17

• Liver has a similar amino acid content as skeletal muscle (3g/kg)
• This pool of amino acids in the liver are primarily used for glucose synthesis via gluconeogenesis
• 18 of the 20 amino acids can be converted to glucose (glucogenic)
• In exercise, an increased secretion of glucagon and a decreased secretion of insulin speed up gluconeogenesis
• 2 cannot be synthesized (leucine and lysine) and are ketogenic
• The liver can also use amino acids from the muscles as precursors for glucose production
• These are glutamine and alanine
• Glutamine is converted back to glutamate, catalysed by glutaminase
• Alanine is converted into pyruvate by alanine amino transferase

Question 18

What is the glucose - alanine cycle?

Answer 18

-Pyruvate (from glycolysis) forms the amino acceptor (transamination) to form alanine (no-essential). Alanine is then transported to the liver where it is converted to pyruvate and glutamate to be used via gluconeogenesis (Citric Acid Cycle) to produce glucose which is then transported back to the muscle to support exercise (up to ~15% total energy demands)

Question 19

Describe the urea cycle (5)

Answer 19

-90% of nitrogen excreted from the human body is incorporated in urea
-Urea is a non-toxic compound bearing two amino groups and is synthesized through four reactions in the urea cycle
-Amino acids from protein breakdown form ammonia during deamination
-Excess toxic ammonia is then ‘neutralized’ and converted to urea via oxidative deamination in the mitochondria of liver cells (hepatocytes)
-The urea cycle and nitrogen balance -> This then links to Ornithine to produce Citrulline. Citrulline is then converted to arginine succinate. Argininosuccinate splits to arginine and fumarate. Finally, arginine is hydrolysed via arginase to form urea.

Question 20

Describe how the urea cycle is affected by exercise

Answer 20

-Plasma ammonia concentrations also increase with exercise. This is related to plasma lactate concentration
-Plasma urea concentrations also increase in exercise lasting >30mins and at an intensity of 60% VO2 Max
-However, during intense exercise plasma urea may not increase further due to a reduction in blood flow to the liver

Question 21

Describe the contribution of proteins to energy expenditure if exercise calculate protein use in exercise

Answer 21

-Total amino acid concentrations in plasma = 3-4mmol/L
-Glutamine and alanine are the most abundant
-During exercise, amino acid concentrations are largely unaffected with durations of ~60 mins
- >2 hours amino acids concentrations decrease ~30%
-1hr of moderate intensity exercise utilizes ~10g of endogenous amino acids (2.5-fold increase)