Biochem Exam Three Clinical Applications

cardiac diet

low sodium, low saturated fat.

who is the cardiac diet used for

heart failure and post-myocardial, hypertensive patients

renal diet

restricted in sodium, potassium, phosphorus. protein may be restricted pre-dialysis or increase during dialysis

consistent carbohydrate diet

consistent amount of carbohydrates at each meal

who is the consistent carbohydrate diet used for

diabetic patients to manage blood glucose

dysphagia diet

texture-modified from pureed to mechanically soft, with thickened liquids to prevent aspiration

who is the dysphagia diet for

patients with difficulty swallowing as determined by a Speech-Language Pathologist

Enteral Nutrition

“tube feeding” delivered into the stomach or small intestines. maintains gut integrity, is safer, and less expensive

Parenteral Nutrition

delivered directly into the blood stream. last resort when the GI tract is non-functional

Obese patients Energy Shortcut: 30-50 BMI

11-14 kcal/kg

Obese patients Energy Shortcut: BMI>50

22-25 kcal/kg

Average Adult (Maintenance) Protein Needs

0.8 g/kg/day

Minor Stress/Post-operative Protein Needs

1.0 -1.2 g/kg/day

Moderate to Severe Stress (sepsis, trauma) Protein Needs

1.2 - 2.0 g/kg/day

severe burns or multi-trauma Protein Needs

up to 2.5 g/kg/day

obese patients (critically ill): BMI 30-40

2.0 g/kg

obese patients (critically ill): BMI > 40

up to 2.5 g/kg

net equation of CAC

acetyl-CoA + 3NAD + FAD + GDP + Pi + 2H2O → 2CO2 + 3NADH + FADH2 + GTP + CoA + 3H

put together the steps of the pyruvate dehydrogenase complex rxn.

1) decarboxylation of pyruvate to acetaldehyde 2) reoxidation of the dithiol lipoamide cofactor 3) formation of acetyl CoA by thioester exchange 4) regeneration of the oxidized FAD cofactor 5) oxidation of aldehyde to a lipoyl thioester

1) 5) 3) 2) 4)

what enzyme converts pyruvate to acetyl-CoA

pyruvate dehydrogenase complex (E1+E2+E3)

Respiration Stage 1:

Acetyl-CoA produced from glycolysis and generates ATP, NADH, FADH2

Respiration Stage 2:

Acetyl-CoA is oxidized by 2CO2 by the CAC. this generates more NADH, FADH2 for ATP production and one GTP

Respiration Stage 3:

Electrons from NADH and FADH2 used to reduce O2 to H2O. creates proton gradient that is used to make ATP from ADP and Pi by the enzyme ATP synthase. 15 molecules of ATP are produced per molecule of pyruvate

overall equation for glycolysis

glucose + 2NAD + 2ADP + 2Pi → 2 pyruvate + 2 NADH + 2 ATP + 2 H2O

what enzyme catalyzes if energy rich phosphate from PEP to ADP to make ATP

pyruvate phosphate

eliminate water from PEP

enolase

sets stage for phosphoenolpyruvate (PEP) formation by rearranging the position of the phosphate so that elimination can give enol phosphate

phosphoglycerate mutase

acyl phosphate of 1,3 - bisphosphoglycerate is energy rich enough to enable thermodynamically favorable synthesis of ATP. named for the reverse reaction the energetically unfavorable phosphorylation of the carboxylate of glycerate.

phosphoglycerate kinase

this energy creates an energy rich acyl phosphate from inorganic phosphate

glyceraldehyde 3-phosphate dehydrogenasw

perfect enzyme.

triose phosphate isomerase (TIM)

enzyme catalyzes the reversible cleavage of fructose-1,6-bisphosphate into two three carbon sugars

aldolase

enzyme catalyzes the first committed step in the glycolytic pathway

phosphofructokinase-1 (PFK-1)

interconverts glucose-6-P and fructase-6-P in a reaction that is nearly energy neutral although the furanose is less stable than the pyranose

phosphohexose isomerase

enzyme catalyzes the first step of glycolysis by selectively phosphorlylating glucose at the 6-position using ATP as energetically favorable phosphate donor

hexokinase

what are the products from pyruvate

2 ethanol + 2CO2 + 2acetyl-CoA* + 2 lactate (from 2acetyl-CoA you can also make 4CO2 + 4H2O)

phase I of glycolysis

preparatory phase that consumes 2 ATP

order the steps of Phase I glycolysis: 1) isomerization to furanose fructose 2)cleavage of the furancose to give two interconverting 3-carbon sugars 3) glucose phosphorylation 4) phosphorylation to give a biphosphate

3) 1) 4) 2)

phase II of glycolysis

Payoff phase - produces energy (+4ATP, +2NADH)

order the step of Phase II glycolysis: 1) interconversion of G-3-P and DHAP to give two molecules G-3-P 2) transfer of enol phosphate to ADP to give 2nd ATP 3) oxidation of G-3-P aldehyde to acid with conversion to acyl phosphate and NADH 4) transfer of high energy acyl phosphate to ADP to give first ATP 5) elimination of water to give high energy enol phosphate 6) rearrangement of phosphate to set up elimination

1) 3) 4) 6) 5) 2)

T/F glycolysis was likely developed before photosynthesis, when the atmosphere was still anaerobic

true

which enzymes of glycolysis phase I are in order

hexokinase, phosphohexose isomerase, phosphofructosekinase-1, aldolase, triose phosphate isomerase

which enzymes of glycolysis phase II are in order

glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate kinase, phosphoglycerate mutase, enolase, pyruvate kinase

type 1 diabetes stage 1

multiple autoantibodies, blood glucose normal, no symptoms

type 1 diabetes stage 2

autoantibodies present (usually multiple), blood glucose abnormal (dysglycemia), no symptoms

type 1 diabetes stage 3

autoantibodies present, blood glucose elevated (hyperglycemia), often symptomatic

Hyperglycemia drivers: T1DM & T2DM

pancreatic insufficiency/eleven “defects”

what does insulin NOT inhibit

glycogenesis(liver)

sulfonylureas & meglitinides

increase pancreatic insulin secretion

sulfonylureas

decrease blood glucose overall

meglitinides

decrease blood glucose after meals

metformin

decreases hepatic gluconeogenesis

increases insulin sensitivity

decrease blood glucose, especially in the morning

heart protection (long-term)

thiazolidinediones (glitzones, TZDs)

PPAR-y activation → improved lipid metabolism and insulin sensitivity

decreases blood glucose overall

secondary ASCVD (heart attack/stroke) prevention

alpha-glucosidase inhibitors (AGIs) MOA

reversible inhibition of intestinal alpha-glucosidase

alpha-glucosidase inhibitors (AGIs) Outcomes

delays breakdown of complex carbohydrates → slows glucose adsorption

elevated postprandial glucose (to prevent high glucose blood peaks after meals)

Dipeptidyl peptidase-4 (DPP-4) inhibitors MOA

inhibits enzyme to increase serum concentrations of glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP)

Dipeptidyl peptidase-4 (DPP-4) inhibitors outcomes

increased insulin release from pancreas beta cells

lowers glucagon secretion from the pancreas alpha cells → reduces liver glucose production

overall reduced fasting & postprandial blood glucose concentrations ; glucose dependent

decreases blood glucose, especially after meals

sodium-glucose transport 2 inhibitors (SGLT2i)

reduce kidney glucose reabsorption into blood

decrease kidney damage from diabetes

protect heart, brain, blood vessels

decreases blood glucose

kidney protection: elevated ACR, decreased eGFR

secondary ASCVD prevention, high risk of primary ASCVD

glucagon-like peptide 1 receptor agonists (GLP-1 RA, GLP1RA) MOA

mimics actions: 1) spur insulin production after a meal but only when blood glucose is elevated 2) suppress inappropriately elevated postprandial glucagon levels 3) promotes satiety & reduces food intake 4) slows gastric emptying 5) and more

glucagon-like peptide 1 receptor agonists (GLP-1 RA, GLP1RA) Outcomes

lower blood glucose overall and especially after meals

kidney protection: elevated AC, decreased eGFR

secondary ASCVD prevention, high risk of primary ASCVD

weight loss

leptin

hormone regulating long-term hypothalamic control of appetite secreted in adipose tissues

what is the best diet for weight loss

no single best diet

which system level intervention is NOT included on the slides: increase access to healthy foods, improve infrastructure for physical activity, encourage workplace and instituitional changes, reduce access to low-nutrient, high calorie foods, set SMART goals, decrease barriers to access to healthcare, enhance community support

set SMART goals

why do GLP-1s help with obesity

target underlying hormonal dysregulation

phentermine/topiramate (Qsymia)

increases norepinephrine→suppresses hunger signals / enhances GABA and inhibits excitatory pathways→reduces appetite and cravings

why does phentermine/topiramate (Qsymia) help with obesity

influence neurotransmitters

bupropion/naltrexone (Contrave)

increases dopamine and norepinephrine→decreases appetite / synergistically when combined with bupropion to dampen the “reward response”→reduces cravings

why does bupropion/naltrexone (Contrave) help with obesity

influences neurotransmitters

alli/xenical (orlistat)

inhibits pancreatic and gastric lipase→reduces breakdown and absorption of dietary fats

unabsorbed fat is excreted instead of stored

why does alli/xenical (orlistat) help with obesity

targets energy intake by directly reducing caloric intake by blocking fat digestion. deters individuals from eating high-fat foods because of the side effects

imcivree (setmelanotide)

MC4R agonist→reduces appetite and increase energy expenditure in individuals with rare genetic conditions that impact the MC4R pathway

why does imcivree help with obesity

addresses the genetic disruption that leads to obesity and increases energy expenditure

restrictive endoscopic bariatric options

reduce gastric volume to delay gastric emptying by endoscopic sleeve gastroplasty or intragastric ballon

metabolic bariatric surgery options

reduces calorie and nutrient absorption by altering digestive tract by laparoscopic sleeve gastrectomy (restrictive) or roux-en Y gastric bypass (restrictive and malabsorptive)

which of the following environmental factors contributes most directly to obesity

increased availability of high-calories, ultra-processed foods