Protein Flashcards
protein functions (6)
- movement
- transport
- structural proteins e.g collagen, elastin, keratin, actin, myosin
- metabolism (partiipate in and regulate)
- communication
- protection against infection
Define protein structures (primary→quaternary)
- primary: the sequence and number of amino acids in a polysaccharide chain
- secondary: bending/twisting of the polysaccharide chain into predictable patterns - pleated sheets, or alpha helix (depends on aa, +/- charges, H bonds and the peptide bonds)
- tertiary: additional folding of the protein due to R groups
- quaternary: multiple polypepdies interacting/creating bonds with one another, can include prosthetic groups ie. hemoglobin
Essential Amino Acids (indispensible) & Non Essential Amino Acids (indispensible)
- Essential: (PVT TIM HLL) - Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Lysine, Leucine
- Non-essential: Almost All American Girls Go Crazy Seeing Antartican Penguins Glide Together - Alanine, Arginine, Asparagine, Glutamine, Glutamate, Cysteine, Serine, Aspartate, Proline, Glycine, Tyrosine
cysteine and tyrosine are “semi-essential”
Situations of Conditionally Essential Amino Acids
- neonates: cysteine, glutamine, glycine, tyrosine, arginine - high requirments, insufficient synthesis (underdeveloped enzyme system)
- increased requirements (stress, injury, fatigue): eg. glutamine
- decreased synthesis: eg. argnine during stress states
- defective synthesis: eg. lacking enzymes - tyrosine
Functions of Glutamine in the body
- amide N donor for DNA biosynthesis
- precursor for glucose formation
- oxidative fuel for intestinal and immune cells
- inter-organtransport of N & C, rid tissues of excess NH₄ (via glutamate)
Functions of arginine in body
- DNA synthesis
- urea metabolism
- CVD implications: arginine promotes NO production, which is a vasodialator and plays a role in CVD
- synthesized mainly in small intestine and kidney (urea cycle)
- ## preterm infants can’t synthesize arginine
Functions of tyrosine in the body
- synthesis of catecholamines/neurotransmitters, melanin thyroid hormones etc…
- when enzyme phenylalanine hydroxylase is not present in the body Phe cannot be converted to Tyr in the body and becomes toxic
catecholamines: hormones involved in the body’s stress respones (epiniphrine, norepiniphrine, dopamine)
Major phases of protein digestion (4)
- mechanical digestion: mixing with saliva in the mouth, minimal if any absorption
- gastric digestion: stomach - mainly chemical, churning with gastric juices
- pancreatic proteases: polypeptides and aa stimulate CCK to be excreted by enteroendocrine cells in the SI, pancreas releases pancreatic juice, zymogens are converted to active enzymes (eg trypsinogen → trypsin via enteropeptidase)
-
hydrolysis of peptide linkages at the brush border:
at the final step of protein digestion, protiens are turning into di/tri peptides and amino acids
gastric juices contain:
1. Hydrochloric acid: denatures proteins, activates pepsinogen to pepsin
2. Pepsin: breaks down small peptides into free aa, inhibits pepsinogen (negative feedback)
Function of pancreatic juice: pancreatic juice contains bicarbonate and enzymes; BC neutralizes chyme from the stomach to allow pancreatic proteases to function (pH 6-7)
Examples of endo/exo pancreatic peptidases
don’t need to memorize; understand
endo: hydrolyze internal peptide bonds within peptide chains
- trypsin, chymotrypsin, elastase
exo: zinc-containing, remove single AA/reaction from one terminal
- carboxyopeptidase A, carboxypeptidase B
Incretins & their significance
a hormone that stimulates insulin secretion in response to meals - supresses glucagon and releases insulin before you get a large spike in blood glucose. decreases fat storage by slowing gastric emptying, promoting satiety and reducing large glucose spikes
- GLP-1: glucagon-like peptide-1 (ozempic mimics GLP-1)
- GIP: glucose-dependant insulinotropic
DPP-4 inhibits GLP1 in plasma
- DPP-4 inhibitors are used in diabetes: extend the life of GLP1
Protein absorption: amino acids vs di/tripeptides
amino acids: facilitated diffusion across the apical and basolateral membranes (want to absorb protein easily)
- different transporters exist for each amino acid! eg aromatics, basic, acidic, etc..
di/tripeptides: H+/sodium dependant cotransport across apical membrane, most broken down into AA in cytoplasm by peptidases, remainder is sent into bloodstream through peptide-transport systems
- intact proteins are not absorbed except in newborn babies as their cell junctions can be leaky
- colostrum: source of proteins for babies, in adults, has positive effects on GIT, proline rich and source of protein
role of enterocytes in aa absorption:
- they may be used for protein synthesis in the cell, energy or conversion into other aa/metabolites
- Gln, Glu and Asp are very important in digestion and synthesizing proteins for the SI therefore show lower portal concentration
significance of hepatic portal system in digestion
first pass metabolism: nutrient rich blood from the stomach and colon go directly to the liver → liver takes what it needs and detoxify’s ensuring harmful substances don’t go to other parts of the body
factors affecting rate of protein digestion
- fast vs slow digesting proteins (eg whey vs casein)
- food matrix (fibre slows digestion by blocking proteins in the lumen)
- oligopeptides > free amino acids
- neutral proteins > basic/acidic
- essential > non essential
regulation of amino acid absorption
- change in intestinal surface area (cells enlargen + multiply in cases such as obesity/pregnancy/diabetes)
- gene expression in the epitelial cells (express more/less amino-peptidases)
Celiac Disease
- gliadin disrupts the intestinal tight junctions so that protease resistant peptides of gliadin can enter enterocytes and produce an immune response
- the body starts to attack the enterocyte cells and cause injury to them leading to decreased digestion
Causes of protein malabsorption
- severe pancreatic dysfunction. (produces digestive enzymes)
- starvation/malnutrition
- intestinal resection
3 metabolic fates of proteins and AA
- protein synthesis
- precursors for non-protein nitrogen-containing molecules
- catabolism w excretion of nitrogen and use of carbon chains for energy
non protein nitrogenous molecules:
- tryptophan → serotonin, nicotinic acid, catecholamines
- tyrosine → catecholamines, thyroid hormones, melanin
Transamination
- occurs in the liver
- an alpha keto acid (⍺-ketoglutarate) transfers an amino group to an AA to create a NEW AA (swap amino groups)
- catalyzed by aminotransferases, enzymes have different outcomes in different tissues
- allows the body to synthesize essential AA and non essential AA, reactions are reversible
- Asp & Ala aminotransferase allow the transfer of amino groups between: glutamate/⍺-ketoglutarate; alanin/pyruvate; aspartate/oxaloacetate
what AA are actively transaminated in human tissues?
Ala, Asp, Glu, Tyr, Ser, Val, Ile, Leu
ALT and AST
ALT: high conc in the liver, found in the kidney, heart and muscle
AST: highest conc in heart, present in liver, skeletal muscle and kidney
- liver disease: blood ALT is higher than AST (AST/ALT ratio <1)
- exceptions; (ratio >2) alcohol hepatitis, cirrhosis, acute hepatitis, bile duct obstruction
ALT: alanine aminotransferase
AST: aspartate aminotransferase
Deamination
- release of free ammonia from AA coupled with oxidation
- mitochondria of kidney and liver
- NH3 enters the urea cycle to be excreted in the urine, alpha keto acids (used in energy production etc..)
- kidney: glutamine deamination, liver: glutamate deamination
Urea Cycle: regulation
Occurs in mitochondria/cytosol of the liver
- arginine and glutamate stimulate synthesis of NAG (when plasma free AA are increased)
- NAG is an allosteric activator of the rate limiting step in the urea cycle (carbomyl phosphate synthetase I)
regulation:
- high protein diet: ↑enyme activity/conc
- early stravation: ↑activity, proteins are degraded so C skeletons can be used for energy, more ammonia excretion
- late starvation: ammonia excretion fails, ↑circulating ammonia = toxicity
low-protein diets recommended for renal disease - can’t excrete toxic ammonia
why is ammonia toxic
- raises pH to a damaging level
- affects the function of ETC and causes irreversible cell damage
- neurtoxicity
free ammonia is produced during catabolism of AA and nucleic acids
Glucogenic & Ketogenic AA
glucogenic: AA can convert into glucose for energy
- C skeletons → pyruvate or CAC intermediates (anaplerosis)
- Ala, Gly, Cys, Ser, Asp, ASn, Glu, Gln, Arg, Met, Val, His, Pro
ketogenic: AA can convert into ketone bodies or fat for energy
- C skeletons → acetyl CoA/acetoacetate
- Lys, Leu
partially ketogenic/glucogenic:
- Phe, Ile, Thr, Trp, Try
when short on energy or glucose, some acetyl CoA is pushed toward ketone synthesis
