Lecture 22 - Fatty acid utilisation and synthesis Flashcards
Essential vs non-essential amino acids
Essential amino acids - cannot be synthesized,
must be obtained from the diet (histidine (H), isoleucine (I), leucine (L), lysine (K), methionine (M), phenylalanine (F), threonine (T), tryptophan (W), valine (V))
Non-essential amino acids can be synthesized (alanine (A), arginine (R), aspartate (D), cysteine (C), glutamate (E), glutamine (Q), glycine (G), proline (P), serine (S), tyrosine (Y), asparagine (N))
Where is nitrogen obtained for organic nitrogenous compounds?
Nitrogen fixation - atmospheric nitrogen N₂ is
converted to ammonia NH₃ by a few diazotrophic
(nitrogen-fixing) bacteria, e.g. Rhizobium
Catalyzed by the enzyme nitrogenase - one of
the most remarkable reactions in biochemistry
Nitrogenase: what is it, what is its structure and what is the reaction it catalyses?
Nitrogenase catalyses the conversion of N₂ into NH₃ using ATP & reducing power (can be incorporated into biomolecules as NH₄⁺)
Tetramer of 2α and 2β subunits and contains a unique iron-molybdenum cofactor
N₂ + 8H⁺ + 8e⁻ + 16ATP ⇄ 2NH₃ + H₂ + 16ADP + 16Pᵢ
Iron-molybdenum cofactor (FeMoco): what is it, what is its central atom, and how much do we know about it?
Primary cofactor of nitrogenase, site of N2 binding and reduction, composition Fe₇MoS₉C
Until 2011 identity of the central atom was a mystery, now it is known to be a carbon atom, Fe₆-carbide species
Unique chemistry and complex biosynthesis,
the mechanism is still being elucidated
Glutamate dehydrogenase: what is it, what does it do, and what are the equations?
Reaction that can occur in either direction in plants and microorganisms but, in mammals, mainly the reverse reaction occurs - incorporates ammonium through glutamate (main chain) and glutamine (side chain)
(1) α-Ketoglutarate, citric acid intermediate,
incorporates NH₄⁺ and forms L-glutamate
α-ketoglutarate + NAD(P)H + NH₄⁺ + H⁺ ⇄ L-glutamate + NAD(P)+ + H₂O
(2) Glutamate incorporates NH₄⁺ into glutamine, catalyzed by glutamine synthetase
L-glutamate + ATP + NH₄⁺ ⇄ L-glutamine + ADP + Pᵢ
The exact organic reaction for ammonium incorporation
α-ketoglutarate -> protonated schiff base -> glutamate
(O₂⁻H₄C₃)-C=O-(COO⁻) + NH₄⁺ -> (O₂⁻H₄C₃)-C=NH₂⁺-(COO⁻) + NADPH -> (O₂⁻H₄C₃)-C-NH₃⁺-(COO⁻)
Transaminases: what do they do with nitrogen in both biosynthesis and catabolism and where are they in humans?
In amino acid biosynthesis, the amino group of glutamate is transferred to α-keto acids, generating α-amino acids
In amino acid catabolism, transamination reactions transfer the amino groups of amino acids to α-ketoglutarate to form glutamate
In mammals, transaminases are liver enzymes,
and in humans, they are a measure of liver
function
All 20 carbon skeletons: where are they obtained from and what are they?
1 - Glycolysis
1,2,3) Pyruvate A,V,L
4,5,6) 3-phosphoglycerate S,C,G
2 - Citric acid cycle
7,8,9,10,11,12) Oxaloacetate D,N,M,T,I,K
13,14,15,16) α-Ketoglutarate E,Q,P,R
17,18,19,20) Pentose phosphate pathway F,Y,W,H
Nitrogen removal within organisms
Marine organisms excrete ammonia directly into
water - ammonotelic
Terrestrial vertebrates convert it to urea in the
liver and excreted urea by the kidneys - ureotelic
Birds, reptiles, and insects synthesize uric acid - uricotelic
Triacylglycerols: what are they and what do they do?
The main form of lipid molecules used in metabolism - energy storage molecules
Long hydrocarbon chains: what are they and how much energy do they have?
Long hydrocarbon chains (-(CH2)n-CH3) the most reduced form of carbon
- Rich in free energy 38 kJ/g (sugars/proteins 17 kJ/g)
Energy storage: what are the two main types and when is either one used?
Triacylglycerols (TGs) and glycogen are the two major forms of stored energy in vertebrates
Glycogen can supply ATP for muscle contraction for less than an hour
Sustained work is fueled by the catabolism of TGs (stored as lipid droplets in the cytoplasm of
specialized fat cells, adipocytes)
Hormone-stimulated lipases break TGs into glycerol and fatty acids
Catabolic paths for glycerol and fatty acids differ
Glycerol metabolism
Glycerol is converted to dihydroxyacetone phosphate (DHAP) in the liver
DHAP is isomerized to glyceraldehyde-3P, intermediate in glycolysis and gluconeogenesis
Fatty acid metabolism: how does it work, what are they used for, how does metabolism work, and where does oxidation occur?
Fatty acids transported in the blood bound to albumin, enter cells via fatty acid transport protein (FATP) and bind to fatty acid binding protein (FABP)
Fatty acids only can be used to obtain free energy, oxidized in the mitochondrial matrix
Activated on the outer mitochondrial membrane by acyl CoA synthetase to form fatty acyl CoA (thioester bond)
Fatty acid + ATP + CoA ⇄ Fatty acyl CoA + AMP + PPᵢ
Fatty acyl CoA is then ready for oxidation in the
mitochondrial matrix (but they cannot cross the inner mitochondrial membrane)
Fatty acid β-oxidation reaction: what is it, what does it do, and how much ATP is generated?
Each round of β-oxidation converts two carbons from the fatty acyl CoA into acetyl CoA, Palmitoyl CoA requires 7 cycles of β-oxidation
8 acetyl CoA (x10 ATP) = 80
7 FADH₂ (x1.5 ATP) = 10.5
7 NADH (x2.5 ATP) = 17.5
Total ATP gain = 108 ATP
Palmitate activation = -2
Net yield = 106 ATP
