Week 4 Flashcards
Describe the necessity for protein in our diet.
What are the three pathways of use in the body?
- Protein → free AA → →
- Essential nitrogenous compounds (trivial)
- Participate in the equilibrium of cell and plasma proteins/nucleic acids/hormone turnover (major)
- Degradation to provide energy from carbon skeleton (10-15%)
Describe the maintenance of the pools of amino acids required for protein synthesis. (in terms of KM)
- KM of aminoacyltransferases is low and therefore prefers to charge tRNA to attract AAs
- Degradation has high KM, or low affinity
- tRNA formation has low KM, or high affinity, favoring protein synthesis
What is nitrogen balance?
- For normal individuals: intake of nitrogen = urea excretion of nitrogen
- Nitrogen balance depends on three things
- N only comes from other AAs (N is never fixed to AAs from outside sources)
- Most waste N excreted as urea
- No dedicated N storage
What is negative nitrogen balance?
Why does it happen?
- Description: nitrogen intake < nitrogen excretion
- Why: individuals are degrading proteins for energy
- Surgery
- Disease
- Trauma (i.e. burns or fractures)
What is positive nitrogen balance?
Why does it happen?
- Description: nitrogen intake > nitrogen excretion
- Why: individuals are in period of growth
- Childhood growth
- Pregnancy
- Post-traumatic event
Describe why some AAs are essential while others are nonessential.
- Essential AAs cannot be synthesized or the body cannot make them in sufficient quantities
- R MLK had HIV WTF
- Nonessential are synthesized in appropriate quantities by the body
What is the relationship of most nonessential AAs to common intermediary metabolites.
- The carbon skeletons of the nonessential amino acids are largely related to common intermediates of metabolism [consider alanine and pyruvate. The reason that the essential amino acids are essential is that we cannot make their carbon skeletons]
What is the general equation for creating different metabolites from AAs?
What is the cofactor?
Name some specific examples?
- General: AA1 + alpha-keto acid2 = alpha-keto acid1 + AA2 (PLP or vitamin B6 as cofactor)
- The Keq of reactions using aminotransferases is ~1, meaning the reaction is dependent on concentrations
- Alpha-ketoglutarate + aspartate = glutamate + oxaloacetate (using aspartate aminotransferase and PLP as cofactor)
- Alpha-ketoglutarate + alanine = glutamate + pyruvate (using alanine aminotransferase and PLP as cofactor)
What does high ALT and AST indicate?
High levels of serum aminotransferases indicate tissue/organ damage (i.e. MI)
How is PLP affected by certian TB treatments?
Isoniazid – used to treat TB – competitively binds to PLP, inducing a B6 deficiency
Describe the importance of the AA composition in the diet.
Any AAs that are not made endogenously are considered essential AAs, and those essential AAs need to be consumed through diet
Describe the inadequacy of certain diets based on vegetable protein.
Vegetarians – have an inadequate consumption of essential AAs
Cereal is low in lysine
Beans low in methionine
Describe Kwashiorkor?
- Inadequate protein intake
- “the disease of the deposed baby when the next baby is born” so no nutrients through breast milk
- Characterized by retention of water in the stomach, failure to thrive, composition of gut bacteria
Describe Marasmus?
- Inadequate energy intake
- Characterized by failure to thrive and delayed mental development
Describe Marasmic Kwashiorkor?
Inadequate energy and protein intake
Describe the occurrence of protein energy malnutrition in anorexia nervosa, bulimia, severe illness, aging.
Occurs in more advanced societies due to inadequate energy and protein intake
Describe the diversity of AA derivatives including post-translational modifications and metabolic products. Give 6 examples.
- 20 AAs are produced through translation into proteins, but lots of AAs are transformed by post-translational modification OR are produced through metabolic processes
- Examples
- Hydroxyproline and hydroxyproline: collagen stability
- Trimethyl-lysine: epigenetic regulation and carnitine synthesis
- Acetyl-lysine: epigenetic regulation
- 3-methylhistidine: modicication on actin and myosine
- Phosphoserine: enzyme regulation
- Gla: binding Ca++
What are proteases?
Proteases hydrolyze the peptide bond
Name some example of extracellular proteases.
- Pepsin in stomach
- Trypsin and chymotrypsin in intestine
- Proteases can be given via oral therapeutics
- CF treated with pancreatic proteases
Name some examples of intracellular proteases?
- Ubiquitin-proteasome pathway: intracellular proteins
- Multiple ubiquitin units must be added to a protein before recognized for degradation to proteasome
- Lysosomes (cathespins): endocytosed proteins and membrane proteins
- Mitochondrial proteases: mitochondrial proteins
What is the urea cycle?
Explian the cycle. (Intermedates and major enzymes)
Describe the role of glutamine in movement of nitrogen.
- Glutamate + NH3 + ATP = Glutamine + ADP+ Pi via Glutamine Synthetase in periphery
- Glutamine + H2O → glutamate + NH3 via Glutaminase in liver and kidney tissue
- Therefore, glutamate acts as a shuttle carrier for NH3
Describe the glucose-alanine cycle and its roles.
What is the difference between NH4+ detoxification in normal people and those with liver cirrhossis? (Describe the pathways)
- Normal: portal vein is high in NH4 → liver detoxifies NH4 → detoxed blood in inferior vena cava
- Liver Cirrhosis: portal vein is high in NH4 → liver cirrhosis → new vasculature forms from portal vein to inferior vena → increased NH4 → blood toxicity
What are some consequences of hyperammonemia?
- Episodic ataxia—muscle weakness
- Dysmetria—uncoordinated movement
- Stupor
- Hepatic coma (encephalopathy)
- Liver Cirrhosis
Describe glucogenic AAs.
Glucogenic: breakdown of glucogenic AAs provide carbon skeletons that enter into pathways making net glucose
- AAs that breakdown to pyruvate or oxaloacetate
Describe ketogenic AAs.
- Ketogenic: breakdown of ketogenic AAs provide carbon skeletons that enter into pathways giving rise to ketone bodies
- AAs that breakdown to acetyl-CoA and acetoacetyl-CoA
Describe the degradation and use of AAs as energy sources.
- Glucogenic: pyruvate or oxaloacetate create a net gain of glucose
- Ketogenic: acetyl-CoA and acetoacetyl-CoA enter into citric acid cycle with no net gain of glucose
What is the source of NO and pathway?
Source: arginine
Arginine + O2 + NADPH → citrulline + nitric oxide + NADP+
Function of NO (4)
Vasodilation (nitroglycerin)
Vascular tone
Inhibition of platelet aggregation
Cytotoxic agent in immune system
What is the importance of Vitamin K?
What does deficiency lead to?
- Vitamin K is a cofactor for post-translational modification of glutamate to Gla
- Vitamin is oxidized, and in order to be used as a cofactor again, it must be reduced through 2 enzymatic steps
- Gla is used in clotting and in osteocalcin (Ca++ binding protein in bone)
- VKDB (Vitamin K Deficiency Bleeding): internal bleeding due to lack of blood clotting (can be mistaken for child abuse)
What are Vitamin K inhibitors?
Dicumerol
Warfarin
Describe translational research.
Bench-to-bedside (i.e. warfarin)
ARSH SAYS – remember the story about the dead cow blood. :)