Block 3 Flashcards
What’s the first vitamin that we have a shortage of during fat malabsorption?
We dont’ store Vitamin K very well so its’ the first vitamin that we have a shortage of during fat malabsorption
What kind of bond holds PLP as a side group? What residue is it attached to? What reactions is PLP required in?
Lysine - schiff base;
PLP used in:
transamination;
Heme synth (ALA synth in HEME pathway);
Dopamine synth (from Tyrosine/Dopa);
GABA formation (from glutamate);
Threonine --> Glycine
Tryptophan --> Serotonin (second step)
Glycogen phosphorylaseWhat calorie source has the highest Respiratory question/DIT?
Carb 1.0 fats 0.7 protein 0.8 RQ
DIT: Protein is highest
What 4 amino acids indicate that the proteins have short half lives? What AA is the most common indicator of short half life?
PEST - Proline Glutamate Serine Threonine;
aspartate on N terminal position is most imp’t 3 minutes h/l
What do transaminases require to remove an NH2? Describe transaminase specificity; what does presence of transaminase in blood signal?
PLP (Vit B6 Pyridoxal Phosphate) attached via schiff base transaminase is specific alpha-keto-acid is not; transaminase in blood signals liver damage
Which isoform of amino acids can we use? What are the 9 essential amino acids? Which are purely ketogenic?
L isoform (D are for dog), pvt tim hall, lysine and leucine
Which amino acids are directly convertible to TCA intermediates?
Aspartate –> OAA
Alanine –> Pyruvate
Glutamate –> A-KG
What nicotinic acid molecules are involved in the amination or deamination of glutamate? Glutamate is the only amino acid that can do what? What enyzme is involved?
NAD-> NADH for deamination NADPH–> NADP; accept free NH3; glutamate dehydrodgenase
What types of AA’s don’t require sodium for their cotransport in the GI tract?
Aromatic (try trp phe) and BCAA (valine leu isoleucine)
Build up of BCAA’s is caused by and results in? WHere does this breakdown normally happen? What are the BCAA’s anyhow?
Defic. in BC k-acid DH (a TLCFN enzyme) results in Maple Syrup Urine disease (MR acidosis sweet smelling urine); Tx: Thiamine (TLCFN) restrict BCAA’s; skeletal muscle; I LV - Isoleucine Leucine Valine
Two methods for protein breakdown? What does each require?
Proteasome with ubiquitin tag on NH2 of Lysine or by Calpain binding to the protein (then autolysis small portion becomes active and proteolytic) requires Calicum
Regulatory enzyme for urea cycle and its substrates? What is it’s activator (and what’s the activator’s activator?)? Most commonly deficient enyzme in pathway and it’s reprecussions? What other condition can that be compared to and what are the differentials? Final enzyme and products in pathway?
Carbomyl Phosphate Synthetase I (Mito) 2 ATP CO2 (bicarb) and NH3/4 (from glutamine/glutamate); NAG; N-acetyl glutamate which itself is activated by arginine; Ornithine Transcarbamoylase failure leads to hyperammonemia and orotic acid build up; differentiate from orotic acid buildup from uridine monophosphate synthetase (from pyrimidine cycle) by hyperammonemia and lack of megoblastic anemia; Final enzyme is arginase producing ornithine and urea
urea cycle failure consequences and affected organs?
Causes hyperammonemia and encapalopthy; a-k-g stolen from TCA leads to energy deficicency; If liver failure you get hepatic encephalopathy (due to aromatic acid building up and damaging nervous tissue; HIGH BUN –> renal damage (kidney not excreting urea); low/normal BUN –> liver damage
PKU: When do you test for it and why?
Minimum 12 hours after birth becuase prior to that PAH (phenylalanine hydroxylase) is not produced;
Amino acids that can be converted to glutamate:
Histidine glutamine; proline; arginine;
What is our primary 1-C carrier? What are it’s two main sources of Carbon?
Tetra-hydroflate and Glycine/Serine
Three things that serine can be converted to (enzyme and cofactor)?
Glycine (serine hydroxy methyl-transfersase FH4) Cysteine (cystathione transferase PLP) Pyruvate (Serine dehydratase (no cofactor gives off free NH4)
Formation of FH4/TH4 from Folic Acid requires what enzyme and cofactors?
Dehydrofolate reductase and 2 NADPH
How does hyperglycinemia present and what is it’s cause? how about histidinemia? Homocystinuria?
hyperglycinemia: severe MR non-stop hiccuping; overabundance of glycine is bad (major inhibitory neurotransmitter due to failure of glycine cleavage enzyme);
histidinemia: usually histidase defic (mental retardation catabolic histidine products in CNS); also may be due to defic in TH4 or Formino Transferase (figlu accumulation in urine)
Homocysteinuria: accum. of homocysteine; methionine; dx: funnel chest resembles marfan CVD (atherosclerosis); Tx: restrict methionine Vit B6
Reactions that require FH4:
Histidine –> Glutamate;
Serine –> Glycine;
glycine cleavage –> CO2/NH3;
homocysteine –> methionine (by way of B12/cobalamin);
What bile conjugate is formed from cysteine? What is cystinosis (mechanism and effects)?
Taurine; Defective lysosomal transporter; leads to photophobia tearing blindiness polyuria glucosuria
Why is Lysine one of the last AA’s that is ever broken down? What cofactor does it’s product require for formation?
Because Lysine is used to make Carnitine (necessary for FA oxidation) requires 3 SAM’s == 9 ATP
What enzyme is at the root of malignant PKU and what is it’s cofactor? Regular PKU?
Dihydropteridine reductase (recycles BH4 using NADPH); Regular PKU is due to defic. in PAH whcih uses BH4 to hydroxylate Phe –> Tyrosine
What are PAPS for and what is their source?
Attach SO4 to sugars (like GAGs) or to make drugs more soluble; made from Cysteine
What reactions is B12 required in? Deficiency results in?
As methyl cobalamin converts homocysteine to methionine also recycles met-FH4 to FH4; without it you get folate trap (all FH4 tied up) pernicious anemia
Source of glyoxylate? What does accumulation lead to?
Glycine oxidation; leads to oxalate buildup/kidney stones
What 5 things can you mke from Tyrosine (and where did you get tyrosine from anyhow)?
Tyrosine comes from phenylalanine; products include: melanin; thyroid hormone; dopamine; norepi; epi
Failure of degradation of Tyrosine leads to 2 conditions; what are they what’s the enzyme involved (cofactor if any) and what are final products of tyrosine breakdown?
Homgentisate oxidate deficiency requires Ascorbate as a cofactor results in alkaptonuria (black urine buildup in joints of elderly; Fumyrlaacetoacetate hydrolase –> tyrosinemia I (cabbage like odor impairment of renal tubular abosrb; liver failure);
Final products: fumarate and acetoacetate
Degradation of Trhyptophan requires what enzyme and cofactor? What essential product does it form? what other two handy things do you get from this breakdown?
Cleavage of pyrolle ring by pyrrolase requires NADPH used to form Niacin/Nicotinc acid (for NADH NADPH); also released ketone and alanine
What are the two initial components of heme? What’s the regulatory enzyme and what down-regulates this enzyme and what cofactors does it have? Any other way heme synth is regulated?
Heme: initial step is regulatory EXCEPT in the bone marrow!!; ALA synthase; requires PLP as cofactor combines Succinyl CoA and Glycine; down-regulated by heme or heme-like hematin (Fe3+); Bone marrow only by Fe availability
How can lead interfere with Heme and what metals is it replacing?
Can substitute for Zn in ALA dehydratase or for Fe++ in ferrochelatase
Most common porphyria? Only one that is AR? Which important one is not photosensitive?
Porphyria Cutanea Tarda (photosensitivity; red-brown urine; uroporphobillinogen decarboxylase creating croproporphyrinogen; CEP (congenital erythropoetic porph; photosens; scarring infections loss of digtis);
Acuite Intermittent Porphyria; no photosensitivity due to porphobillinogen deaminase (that takes 4 porphobillinogen and makes them into a ring hydroxymethylbilane)
What specifically breaks down heme using what initial enyzme? What is the intermeidate product and what is it converted to? What’s special about the iron that comes out of Heme and what do you have to do about that specialness?
Macrophages in the spleen; enyzme is heme oxygenase (a P450 that contains Heme) which generates biliverden; biliverden reductase converts that to billirubin which is carried by albumin to the liver; Iron from heme breakdown is Ferric (Fe3+) so has to be reconditioned to Fe2+ by Vitamin C
What does the liver do with bilirubin and with what enzyme? When this product is secreted what three things does it become during breakdown?
In liver billirubin is conjugated with 2 glucuronates by bilirubin glucuronyl-transferase; conjugated bilirubin is secreted as bile and broken down by bacteria to urobillinogen; further broken down to urobillin (excretion in urine) or stercobillin (excretion in feces)
Describe the three kinds of jaundice (hemolytic neonatal and nuclear) as well as dubin-johnson syndrome
Hemolytic jaundice: massive break down of RBC’s (malaria sickle cell) overwhelms liver;
Neonatal jaundice: neonate has lg. amount of Hb that needs to be broken down along with naturally low glucuronyl transferase activity;
nuclear jaundice: bilirubin accumulating in lipid rich area of brain - CNS issues ensue
Dubin-Johnson: failure to secrete bilirubin into bile leads to black liver hyperbilirubinemia
Products of Arginine? Which involves vasodilation and clotting and in what way for each? what popular drug takes advantage of this process?
urea Nictric oxide and creatine; Nitric oxide is released (and produced) by endothelium prevents platelet aggregation (also immunogenic) relaxes vessels through guanylate cyclase production of cGMP (much like cAMP release in smooth muscle); viagra
Creatine synthesis involves what two AA’s? What does creatine randomly break down into?
Creatine is formed from combination of arginine and glycine (releasing ornithine); creatine phosphate spontaneously cyclises to creatinine and is excreted in urine
Which amino acids or products are neurotransmitter?
Glutamate --> GABA Serine --> Glycine (inhibitory) Arginine --> NO Tyrosine to Dopamine Norepi Epi Tryptophan --> serotonin
Two ways to get rid of histmaine?
Diamine oxidase in peripheral tissue (releases free NH4)
SAM and MAO-B in brain (MAO also breaks down catecholamines)
What produces Serotonin and what cofactors are involved? What is Seratonin later converted to (and using what two cofactors) ?
Tryptophan using tryptophan hydroxylase (with BH4) then dopamine decarboxylase (PLP);
Serotonin gives rise to melatonin using AcetylCoA and SAM
Two ways to get rid of histmaine?
Diamine oxidase in peripheral tissue (releases free NH4)
SAM and MAO-B in brain (MAO also breaks down catecholamines)
What produces Serotonin and what cofactors are involved? What is Seratonin later converted to (and using what two cofactors) ?
Tryptophan using tryptophan hydroxylase (with BH4) then dopamine decarboxylase (PLP);
Serotonin gives rise to melatonin using AcetylCoA and SAM
