Protein Digestion Flashcards
Describe nitrogen balance
- Body protein state of lux all the time (continually turned over)
- Protein broken down, Amino acids enter pool so available for other purposes (re-conversion, energy as metabolised to glucose and ketone bodies)
- Ammonia- urea= excretory
- Dietary protein= replenishes pool
- Nitrogen balance= (Total N ingested) - (Total N excreted)
What is the recommended daily protein intake?
0.8 grams per kilogram body weight per day
40/50 grams per person per day
-Nursing and athletes need more protein
What is net protein utilization (NPU)?
- Measure of the ability of a protein to sustain growth/ quantify nutritional value of protein
- weight. amino acids incorporated into protein / wt. amino acids supplied in diet
- %= human milk (95), egg (87), cow’s milk (81)
What are the essential and non-essential amino acids?
-Essential= cannot be synthesised within body (diet)- carbon skeletons too complex =Leucine =Lysine =Valine =Methionine =Tryptophan =Isoleucine =Phenylalanine =threonine -Non-essential= can be synthesised from other amino acids in diet -Arginine and histidine= capacity to synthesise but not at rate required for protein turnover -High NPU
What are the ketogenic amino acids?
-Leu
-Lys
Also glucogenic
-Ile
-Phe
-Trp
-Tyr (not essential)
What is Kwashiorkor?
Children having body weight between 60 and 80% of that expected for their age
- Swollen bellies (enlarged liver, oedema due to albumin deficiency)
- Muscle wasting, diarrhoea
What is Marasmus?
- Body weight less than 60% of the expected value for the person’s age
- Protein and calorie deficiency
- Monoculture sources of protein in diet
What are the different imbalances of nitrogen?
- Positive= growth, pregnancy (more body protein synthesised than degraded)
- Negative= protein deprivation, essential amino acid deficiency, trauma/ disease
What are the half-lives of proteins?
Insulin= mins Intestinal= 1-2 days Fibrinogen= 3 days Albumin= 20 days Haemoglobin= 120 days Collagen= months Crystallin (life)
Describe degradation of extracellular proteins
- Taken up by cell in endocytosis
- Binds to a receptor or series of receptors, receptors then internalised to form closed compartment (endosome)
- Fuse with lysosomes (degradative organelles, low internal pH)
- Membrane returned to surface, releasing amino acids
Describe degradation of intracellular proteins
- Tagged by the attachment at the C-terminus of ubiquitin (76 amino acids long)= label
- Degradation by protein complex (proteasome)= ATP-dependent process
What was the action of thalidomide?
Alter specificities of the enzymes which attach ubiquitin to proteins for degradation
- Some transcription factors degraded prematurely, other survive too long
- Altered expression of lots of different proteins
Describe degradation of dietary protein
- Chief cells in gastric pit of stomach produce pepsin= gastric acidification
- Pepsin prefers large hydrophobic amino acids like phenylalanine or leucine
- Stomach contents neutralised by pancreatic secretions- high concentrations of bicarbonate
How is gastric acid produced by parietal cells?
- Structure maximised plasma membrane area
- Proton concentration high at apical side/ lumen (0.8)- different protein composition= gastric ATPase (proton pump)
- At basolateral side, pH= 7.4, transport proteins for anions
- Protons come originally from carbonic acid (hydration of CO2, formed by oxidative metabolism)- to gastric lumen and bicarbonate
- Bicarbonate stays within cells= alkaline= exported into plasma in exchange for Cl-
What drugs treat gastric ulcers?
- Omeprazole, vonoprazan
- Inhibitors of gastric ATPase
What is achlorhydria?
Secretion of HCl fails
Uptake of vitamin B12, binds to protein called intrinsic factor
Describe secretion and activation of pepsinogen
- Hazardous to synthesise degradative enzymes in cell so secreted as inactive precursors (zymogens)
- Chief cells
- Regulated exocytosis
- Protein made in cytoplasm, introduced into lumen of ER, passes to Golgi apparatus, buds off in secretory vesicles
- Stimulus= acetylcholine
- Converted to pepsin when encounters H+ (autocatalysis)
Examples of proteinases
- Trypsin hydrolyses bonds on carbonyl side of basic amino acids arginine or lysine
- Chymotrypsin= large, neutral amino acids phenylalanine
- Elastase= small neutral
- Carboxypeptidases= release C terminal amino acids- A (neutral), B (basic)
Cascade of activation of pancreatic zymogens
- Trypsinogen to trypsin (activated by enteropeptidase/ enterokinase)
- Chymotrypsinogen to chymotrypsin
- Proelastase to elastase
Describe the transamination reaction
-Transamination
=catalysed by transaminases/ aminotransferases
=Amino group transferred onto oxoglutarate, (converts amino acid to oxo-acid) oxoglutarate converted to a different aminoacid glutamate
Describe the oxidative deamination reaction
=Removed from glutamate in mitochondria via glutamate dehydrogenase (oxidises glutamate back to oxoglutarate, reduces NAD to NADH= oxidative deamination)
=Amino group liberated as ammonia
=Ammonia essentially inhibits TCA cycle
How do we remove ammonia?
-Reacts with CO2 and is phosphorylated= carbamyl phosphate in mitochondria
=Reacts with intermediate ornithine, transfers amino group to form citrulline
-Citrulline receives another amino group that comes from glutamate indirectly by aspartate (glutamate transaminated with oxaloacetate)
=Arginine broken down to release urea
-Incorporated into urea in liver only
Describe amino acid breakdown in peripheral tissues
- Doesn’t synthesise urea so amino groups transported to liver
- Alanine transported, formed when glutamate transaminated with pyruvate
What are the properties of urea?
- Very soluble in water
- Electrically neutral: neither acidic nor basic
- 48% N by weight
- Synthesised in liver so not further metabolised
- Normal plasma 2.5-7 mmol/l (rises in renal failure- uraemia, falls in liver cirrhosis/ deficiency in urea cycle enzymes)
- Plasma ammonia normally low (12-60 micromole/l) but rises if urea cycle inhibited (liver cirrhosis)
- Ammonia is toxic, particularly to CNS
How is urea excreted from the kidneys?
- Ammonia liberated by glutamate dehydrogenase
- Can be used to convert glutamate to its amide, glutamine
- Glutamine transferred through plasma to kidneys where glutaminase takes amino group off to form ammonia
- Liberated directly into urine by kidneys
Overview of amino acid metabolism
- Amino acids are transaminated to form carbon skeletons which are oxidised to CO2 if they are used as fuel
- Amino acids undergo transamination, amino group in glutamate and transported to liver from peripheral tissues via alanine
- Alanine backaminated to glutamate, feeds amino-groups into urea cycle as either ammonia via carbamyl phosphate or transamination to aspartate, excreted in urine by kidneys
- In starvation= amino acid group in glutamate, liberated as ammonia, amide of glutamate- glutamine, transported through the blood
Difference between gluconeogenic and ketogenic amino acids
- If amino acid broken down to acetyl-CoA= ketogenic
- If amino acid broken down to a TCA cycle intermediate, can be converted back to glucose= gluconeogenic
What is one-carbon metabolism?
-Set of reactions in which single-carbon fragments from aminoacid breakdown are metabolised (glycine, serine, histidine, tryptophan)
-Metabolised by being attached to tetrahydro-folic acid
-Folic acid= vitamin, utilised as a coenzyme, reduced twice
-Tetrahydofolic acid acts as carrier of one-carbon groups (formyl, formamino)
-Oxidised and reduced
=Important ingredients in synthesis of compounds like purine, thiamine, methionine
What is pernicious anaemia?
- Autoimmune destruction of parietal cells in digestive tract
- Fail to secrete a protein called intrinsic factor
- Vitamin B12 not absorbed
- Failure of one-carbon pathway
- Affects DNA replication
Use in drugs (folic acid inhibitors)
- Cycloguanil = inhibitor of dihydrofolate reductase
- Trimethoprim in malarone
- Methotrexate anti-tumour drug
Describe the action of sulphonamide
- Mimics part of the folic acid structure
- Acts as inhibitor of folic acid synthesis in bacteria
Describe the action of methotrexate
- Analog of folic acid
- Inhibits dihydrofolate reductase
