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23 Cards in this Set
- Front
- Back
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Where do amino acids come from
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Dietary protein, digested by proteolytic enzymes. Amino acids and small peptides released and get absorbed through intestine and into circulation. Translation occurs from the amino acid. |
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Protein turnover
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Cellular proteins constantly degraded and resynthesized, some remain in cell due to long half life. - normal cellular and physiological processes: cell cycle, apoptosis by caspases - remove damaged proteins: aggregate and cause serious neurological problems e.g. Parkinson's - source of amino acids (300-400g protein degraded per day, daily intake around 100g) |
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How is protein turnover tightly regulated?
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Specific mechanisms to label proteins destined for degradation e.g. ubiquitin is a cell marker - form proteasome - releases peptide fragment and ubiquitin is recycled. |
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Breakdown of protein due to starvation, diabetes and trauma/severe injury
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Starvation - provide cellular fuels so brain and body can survive Diabetes - muscle breakdown, as body not taking up glucose: starvation in times of plenty Trauma and severe injury - protein breakdown and release of amino acids. Shock reaction, hypermetabolic or flow phase, restorative phase where tissues build up again |
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The hypermetabolic phase of trauma
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Increased heat production and metabolic expenditure. Fat metabolism - energy Muscle protein degradation - amino acids Increase in substrate and fuel supply for survival and repair |
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Essential and non-essential amino acids
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Essential - cannot be made endogenously so must be supplied by the body (made by plants) Non-essential amino acids - made endogenously by single step reactions. Excess amino cannot be stored so must be broken down and excreted. If essential AA not supplied continuously then muscle loss occurs. |
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The controllers of protein breakdown
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Hormones: insulin promotes synthesis and amino uptake into cells using AA transporters. When insulin low (in starvation) it promotes protein breakdown, mediated by proteases
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What are amino acids needed for in the body?
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Protein synthesis Cellular fuel - TCA cycle for energy or gluconeogenesis to make glucose Precursors for biosynthesis - glutamate converted to neurotransmitter in brain, in adrenal medulla adrenaline made from tyrosine Glutamate, glutamine and aspartate - amino donors in transamination. Serine - lipid biosynthesis Glycine - porphyrin synthesis Arginine - NO (signalling molecule) |
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Catabolism of amino acids
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1. amino group removed (NH2) and transferred to glutamate by amino transferases 2. amino acid released as ammonia and excreted as urea 3. carbon skeleton converted for entry into TCA cycle for energy or gluconeogenesis pathway to make more glucose. |
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Amino transferase enzymes
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Catalyse reaction using pyriodoxal phosphate prosthetic group from Vit B6. Different enzyme for different amino acids - covalent catalysis. Amino groups channelled to glutamate
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Glutamate dehydrogenase
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releases amino acids as ammonia using NAD or NADP. Inhibited by ATP and GTP and stimulated by ADP and GDP. If very high ammonia (toxic) then it can reverse and be used for glutamate synthesis. Glutamate converted back to 2-oxo glutamate Located in mitochondria, after NH3 released it enters urea cycle |
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Different groups of amino acids depending on fate of carbon skeleton
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Glucogenic - degraded to pyruvate or other TCA intermediates. Can be converted back to glucose as they supply gluconeogenesis e.g. alanine, serine, cysteine, aspartate (oxaloacetate) Ketogenic - degraded to acetyl coA or caetyl acetate. Converted to ketone bodies e.g. leucine (acetyl coA) or lysine Mixed - different parts of carbon skeleton form different parts. e.g. phenylalanine and tyrosine (fumarate and acetoacetate), phenylalanine hydroxylase (phenylalanine to tyrosine). |
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Final fate of ammonia and urea synthesis/breakdown
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Excreted as urea or uric acid in bird/ammonia in fish Urea synthesis - liver. Urea cycle occurs in mitochondria and cytosol, controlled by compartmentalisation. Urea excreted via kidney |
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The urea cycle
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1- ammonium ions + CO2 -> carbamoyl phosphate using carbomoyl phosphate synthase 2 - reacts with ornithine to produce citrilline 3 - citrulline transported into cytoplasm and reacts with aspartame to produce arginosuccinate 4 - splits to produce fumarate and arginine - fumarate enters TCA cycle 5 - arginine broken down to produce urea and ornithine, transported back to mitochondria and recycled to produce citrulline.\ |
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The urea cycle continued
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Cyclic process, one amino group in urea comes from ammonium ions the other from the amino group in aspartame. Argionosuccinate and fumarate are a major link with the TCA cycle. Urea synthesised from aspartate, ammonia and CO2 |
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Amino acid degradation
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Mostly in liver but can be in other tissues e.g. muscle during fasting or exercise. - amino acids released and transferred to pyruvate to form alanine - amino group transferred to liver from muscle as alanine - glucose- alanine cycle occurs in two modes: normal and starvation |
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The glucose alanine cycle
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1 - protein broken down in muscle to branched chain amino acids 2 - transaminated to release ammonium ions 3 - NH4+ + pyruvate -> alanine 4 - remaining carbon skeletons used in TCA cycle to provide energy . Alanine can remove ammonium ions in tissue that lacks enzymes of urea cycle - it exists through liver. 5 - alanine broken down to pyruvate and glutamate to release amino group in urea cycle within liver 6 - pyruvate feed into gluconeogenesis to supply glucse or into glycolysis. |
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The glucose-alanine cycle in starvation and in other tissues
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Glucose uptake into muscle is low - insulin low so GLUT-4 activity is low. Glucose must be maintained in blood to supply glucose to brain Muscle lacks enzymes to convert NH3: amino group transferred to pyruvate to provide alanine. In other tissues amino group transferred to liver as glutamine, glutamine synthase used to add NH4+ to glutamate to form glutamine. |
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The regulation of the TCA cycle
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Provide 8 high energy electrons (6NADH and 2FADH2) - availability of acetyl coA: feed forward if availability high - enzymes inhibited by NADH as shows energy high. Isocitrate-> alpha ketoglutarate inhibited by ATP and NADH and stimulated by ADP. Conversion to succinyl coA inhibited by ATP, succinyl coA and NADH (products) - lack of O2 it will shut down due to build up of NADH |
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Oxidative phosphorylation location, regulation, ETC |
inner mitochondria membrane on cristae (TCA occurs in mitochondrial matrix). Transport -double membrane provides regulation, enzymes need to arranged in correct order along mitochondrial membrane. ETC - transfers electrons from NADH and FADH2 to oxygen and drive ATP synthesis |
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The two reactions occurring in oxidative phosphorylation
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NADH + oxygen -> NAD+ + water ADP + Pi -> ATP Conversion of oxygen to water drives a proton gradient which is used to drive ATP production (tightly coupled). Oxygen only reduced when ADP synthesised so regulated by substrate availability. Rate of electron transport controlled by ADP - activated when ATP consumed |
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The uncoupling of oxidative phosphorylation in some organisms
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Uncoupled from ATP synthesis to generate heat and maintain body temperature in hibernating animals/newborn babies BAT - non shivering thermogenesis occurs. Rich in mitochondria and mitochondrial membranes. Allows influx of protons without ATP synthesis |
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The importance of regulation of oxygen reduction
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- transfer of 4 electrons to molecular oxygen leads to generation of two water molecules - partial reduction forms hazardous compounds: transfer of one electron = superoxide ion, two = peroxide ion. Very destructive reactive oxygen species, especially to DNA - enzymes made e.g. superoxide dismutase which converts superoxide radicals to H2O2 and catalase converts H2O2 to water. - need for dietary antioxidants, exercise increases superoxide dismutase in cells. |
