Protein Nutrition (N Balance) and Metabolism Flashcards
What happens in carbohydrate and lipid metabolism?
Primarily involves the incorporation and excretion of carbons, oxygens, and hydrogens
Carbons primarily oxidized to carboxylic acids and excreted as CO2 from the TCA cycle
- Any cell with mitochondria can carry out TCA cycle
What contains nitrogens?
Proteins and nucleic acids
Where does excretin of small molecules containing nitrogen (urea, uric acid, NH4+) take place? How do other cells get rid of excess nitrogen?
Liver and kidneys
other cells: excretion of water-soluble, non-toxic molecules to be carried via the bloodstream to the liver and kidneys
What happens to amino groups after being removed from amino acids?
Carbon skeletons can be completely degraded to CO2 by entrance into the TCA cycle to directly provide ENERGY
OR
some of them can be used to synthesize glucose via gluconeogenesis or synthesize ketone bodies
What are some key facts about protein/amino acid metabolism?
Proteins serve FUNCTIONAL purposes (i.e. serum albumin, muscle) - are not energy stores
Proteins are constantly ‘turned-over’ in the body
Amino acids are also not stored - only small pools of amino acids are readily available
Amino acids are REQUIRED for synthesis of other nitrogen compounds
Continuous loss of nitrogen from the body - regardless of amount of intake (5-7g N/day ~40g protien)
A diet low in protein is eventually FATAL
What is nitrogen balance?
How much nitrogen is excreted? Does protein intake affect excretion?
the difference between TOTAL N intake vs. TOTAL N loss (Nin vs. Nout)
Positive nitrogen balance (i.e. growing child): Nin > Nout
Nitrogen equilibrium (i.e. adult): Nin = Nout
Negative nitrogen balance (i.e. starvation, protein deficient diet): Nin < Nout
If NO protein intake, still excrete nitrogen at ~5-7g/day
If one essential amino acid is missing, cannot synthesize most proteins which generally require all 20 amino acids
What are essential amino acids?
the carbon skeletons either cannot be synthesized at all or cannot be made in sufficient quantities
essential amino acids MUST be obtained in the diet DAILY
What are the 10 essential amino acids?
Arginine (R)
Histidine (H) *required in small quantities because adults effeciently recycle histidine; children and pregnant women have increased requirement
Isoleucine (I)
Leucine (L)
Lysine (K)
Methionine (M)
Phenylalanine (F)
Threonine (T)
Tryptophan (W)
Valine (V)
What are the tips for remembering the essential amino acids?
Any Help In Learning These Little Molecules Proves Truly Valuable
PVT TIM HALL
One-letter codes: The Whole Food Larder Really Must Have Various Key Ingredients
Why is protein required in the diet?
Need the essential amino acids and replace continuous nitrogen excretion
For synthesis of important nitrogen containing compounds; Ex: nucleotides, porphyrins, transmitters
Source of energy
How much protein from the diet is required?
Depends on:
- Protein quality
- Energy intake from other sources
- Age and activity
What is protein quality?
the content and balance of amino acids
digestibility = how much is absorbed
What are the methods for evaluating protein quality?
biological value (BV): based on nitrogen absorption
Biological Value (BV) = N retained / N taken in * 100
Highest BV = 100%
What is the Protein Digestibility-Corrected Amino Acid Score (PDCAAS)?
based onthe profile of essential amino acids after correcting for digestibility of protein
Highest PDCAAS = 1.0
How is protein quality determined by the amino acid composition?
Content of the essential amino acids
Proportions of the essential amino acids compared to human proteins
- Closer the match between dietary proteins and human proteins, the better the protein quality
- Proteins of animal origin have a high quality
- Other proteins: proteins from plant sources have lower quality than animal protein
- Wheat gluten = 0.4 because low in tryptophan and lysine
- Beans = low in methionine
- Corn = low in tryptophan and lysine
How does one overcome low protein quality?
mixtures of vegetable proteins
Examples:
- diet with corn/wheat (both low in tryptophan and lysine) + beans (low in methionine) -> combined high nutritional value
Define liquid protein diets.
some are based on gelatin
- gelatin is mainly glycine, proline, and hydroxyproline
- gelatin = 0.08 (low amounts of most essential amino acids)
What are the differences in protein digestibility that affect the protein quality?
Problem: accessibility to water-soluble digestive enzymes may be limited
- physical form of protein may be inaccessible
- ex: whole grains - seed coat prevents access by digestive enzymes
Solution: process or cook
- grind to flour, allows better access
- cooking (even better)
- wet heat = more digestible
- dry heat = less digestible -> loss of lysine, cross-linking (less accessible)
What is Kwashiorkor?
occurs when protein is starved, but adequate carb calories
results in severe loss of visceral protein
What are the symptoms of Kwashiorkor?
stunted growth, edema, skin lesions, depigmented hair and skin, anemia, enlarged fatty liver, and decreased plasma albumin concentration
- typically see deceptively plump belly due to edema
When does kwashiorkor begin to occur?
~1 year of age when child is weaned and diet is mostly carbs
What is Marasmus?
occurs with protein and energy starvation
observe general wasting and no fat deposition
What are the symptoms of Marasmus?
stunted growth, emaciation, weakness, and anemia
do NOT see edema and plasma protein changes as in kwashiokor
When does Marasmus begin to occur?
usually observed in children younger than 1 year of age when breast milk supplemented with grains deficient in proteins and calories
What are important facts about Protein Energy Malnutrition (PEN)?
It is observed in developing countries:
- medical conditions that changes how nutrients are digested/absorbed
- medical conditions that decrease appetite
- hospitalized patients with major trauma or infections
- malnourished children/elderly
More common in developing countries due to an inadequate intake of protein and/or energy
What is a symptom of PEM?
Depressed immune system with a reduced ability to fight infections leading to death from secondary infections
- immunologic effects of protein deficiency: decreased size of thymus, decreased DTH response, decreased Tregs, decreased complement levels
What is the digestion/absorption of proteins?
The breakdown of proteins (which are generally too large to be absorbed) to their constituent amino acids, which can be absorbed by the intestine
- Example exception: newborns can absorb materinal antibodies from breast milk
Why are proteins digested/absorbed?
Most of the nitrogen in the diet, which is necessary for synthesis of nitrogen-containing molecles, is consumed in the form of proteins
Where are proteins digested/absorbed?
The stomach, the pancreas, the small intestine (intestinal mucosa)
- all have different sets of proteases and peptidases to cleave proteins/oligopeptides
How are proteins digested/absorbed?
All digestion processes involve hydrolase enzymes
What are hydrolases?
enzymes that add H2O across a bond to break it
What are proteases?
class of hydrolases that cleave peptide bonds of proteins into smaller polypeptides or oligopeptides (can also yield free amino acids)
What are peptidases?
class of hydrogens that cleave peptide bonds of small polypeptides and oligopeptides to ultimately remove free amino acids
- endopeptidases: cleave peptide bonds in the middle of the protein chain
- exopeptidases: cleave proteins at either end
- aminopeptidase: cleave at NH2-terminus
- carboxypeptidase: cleave at COOH-terminus
How does the stomach digest proteins?
secretes gastric juices containing hydrochloric acid and pepsinogen
What does hydrochloric acid do in regards to protein digestion?
pH = 2-3
kills bacteria
denatures proteins (more susceptible to hydrolysis of proteases)
activates zymogens
What is pepsinogen and how does it relate to protein digestion?
zymogen (pro-enzyme) - inactive form of pepsin
have extra amino acid sequences preventing catalytic activity
removal of these sequences permits catalytic activity
What is pepsin?
the active enzyme form derived from pepsinogen
activated by HCl or by autocatalysis from other pepsin molecules
an endopeptidase: specific for internal hydrophobic amino acids
How does the pancreas assist in digesting proteins?
Stores zymogen form of proteases and peptidases packaged in vesicles (as a ‘double control’ - trauma to pancreas can release them, causing serious damage)
digestive tract hormones trigger release of zymogens into the small intestine
How does the small intestine digest proteins?
Enteropeptidase - released by intestinal mucosal cells converts the zymogen trypsinogen to trypsin
Trypsin converts other trypsinogen molecules to trypsin
Trypson is also the common activator of all the pancreatic zymogens
Active proteases/peptidases: digest polypeptides from stomach to smaller oligopeptides and free amino acids
What are abnormalities in protein digestion clinically relevant?
caused by deficiency in pancreatic secretion due to:
- chronic pancreatitis
- cystic fibrosis
- surgical removal of pancreas
digestion and absorption of fat and protein are incomplete
results in:
- abnormal apperance of lipids in feces (steatorrhea)
- undigested proteins
What is celiac disease?
disease of malabsorption
caused by immune-mediated damage to the small intestine in response to ingestion of gluten (or gliadin produced from gluten)
gluten is a protein found in wheat, barley, and rye
How do intestinal mucosal cells digest proteins?
contain on luminal cell surface
- aminopeptidase: an exopeptidase that repeatedly cleaves off amino acids from N-terminus of peptides 3-6 amino acids long
- result: produces free amino acids and smaller peptides
- dipeptidase: cuts peptides 2 amino acids long to release 2 free amino acids
How do the intesinal mucosal cells absorb proteins?
free amino acids and dipeptides are absorbed, but the dipeptides are cleaved by the dipeptidases
only free amino acids are released into the portal system
free amino acids are metabolized by the liver or released into general circulation
How are amino acids taken up by cells?
Energy dependent
- some coupled to Na+-gradient (ATP used)
- some coupled to gamma-glutamyl cycle (ATP and GSH used)
Many specific transport systems for amino acids
- separate carriers for:
- large, neutral amino acids
- small, neutral amino acids
- proline and glycine
- basic amino acids
- acidic amino acids
- genetic defects in these transport systems
- cystinuria = genetic defect in carrier system for cystine and dibasic amino acids
How are peptides absorbed?
occurs more in newborns (e.g. antibodies from breast milk absorbed as intact protein); less in adults
mechanism: transcytosis
- What is protein turnover?
- How much is degraded?
- At what rate?
- What does it facilitate changes in metabolism in response to?
- Why is there protein turnover?
- degradation of body proteins to amino acids and resynthesis of new proteins from the amino acid pool
- 300-400g protein/day, regardless of intake amount; 40g protein excreted
- proteins have intrinsically different rates of turnover
- t1/2 depends on tissue, function and metabolic state
- HMG-CoA reductase: t1/2 = 30mins
- Aldolase: t1/2 = 100hrs
- Chondroiton: t/12 = 10 days - turnover facilitates changes in metabolism in response to: nutrient intake, activity, hormones
- need different sets of proteins and enzymes to process these new demands
- high fat diet -> requires enzymes for fatty acid oxidation and gluconeogenesis
- high CHO diet -> requires enzymes for glycolysis and fatty acid synthesis
What is protein catabolism?
the breakdown of endogenous (body) proteins to their component amino acids
Why is protein catabolized?
prevents buildup of abnormal or unwanted proteins
recycles amino acids for re-synthesis of proteins
to provide carbon skeletons for energy, ketone bodies, or glucose
Where is protein catabolized?
cytosol and lysosomes of all cells
How is protein catabolized?
two systems:
- lysosomal pathway
- ubiquitin-proteasome proteolytic pathway
What is the lysosomal pathway of protein degradation?
non-energy dependent pathway
lysosomes contain numerous proteases for protein degradation (acid hydrolases)
degrades intracellular proteins (autophagy) and extracellular proteins (heterophagy)
What is the ubiquitin-proteasome proteolytic pathway of protein degradation?
ATP-dependent pathway in the cytosol of all cells
‘programmed destruction’ - proteins targeted for degradation
ubiquitin - a small, globular protein
proteins attached to ubiquitin (actually a small polymer of ubiquitin) are ‘targeted’ for degradation
proteasome - a large ‘barrel-like’ complex that degrades the ubiquitin-targeted proteins
What are the results of protein catabolism?
- excess amino acids are NOT stored; if not required for synthesis - degraded
- carbon skeletons of amino acids -> TCA (used for energy, to make ketone bodies, or to make glucose via gluconeogenesis)
- amino group (-NH2) -> mostly excreted
- degradation of functional proteins to amino acids can provide energy - but at a LOSS of function
Note: glycogen and fat are broken down WITHOUT loss of function
What happens in starvation conditions?
carbohydrates used first - will be used up in first 24hrs
fat used ‘next’ (or simultaneously) - takes weeks to use up fat stores
protein mobilization initially occurs for metabolic changes
major protein breakdown is pathological:
- serum albumin is broken down -> edema
- liver and muslce protein broken down -> dysfunction
