Nutritional Biochem Exam 2

What is diabetes mellitus?

endocrine disorder, alteration in cellular transport/metabolism of glucose

What are some causes of diabetes mellitus?

1) insufficient insulin release

2) lack of insulin receptors

3) inability of insulin receptors to transduce signal

What characterizes Type 1 diabetes?

Insulin Dependent Diabetes Mellitus (IDDM): common form is non insulin producing B cells (autoimmune destruction of pancreatic islet B cells)

• more common in dogs but cats also diagnosed

What characterizes type 2 diabetes?

Non-Insulin-Dependent Diabetes mellitus (NIDDM): results from impaired insulin secretion combined with impaired insulin action, which is also referred to as decreased insulin sensitivity or insulin resistance

• complex etiology, caused by a combination of genetic factors and environmental interactions, and risk increases with aging.

• more common form in cats

What factors should be considered with Diabetes Mellitus?

• overall health/body condition

• presence of other diseases

• type of diet

• nutrient composition of diet

• nutritional adequacy of diet

• animals energy requirement

• feeding

What are some factors that may result in the manifestation of hypoglycemia?

• excess glucose utilization and inadequate glycogen stores

• hypersensitization of insulin

• deficiency of enzymes required for glycogenolysis

true or false: Given that the Gross energy (GE) derived from corn is equal to that of wheat straw, when fed to a dog the Metabolizable energy (ME) derived from corn would likely be greater than the energy that is derived from the wheat straw?

True

In a patient with a glycogen storage disorder that impairs glycogen breakdown (glycogenolysis), how would gluconeogenesis compensate for the lack of available glucose during fasting?

Gluconeogenesis would increase the use of non-carbohydrate precursors like amino acids to produce glucose.

In a patient with an insulin resistance disorder, such as Type II diabetes, how would impaired insulin signaling affect glycogen synthesis in the liver and muscle?

Glycogen synthesis would decrease because insulin normally promotes the activation of glycogen synthase, and impaired insulin signaling would prevent this.

The Cori cycle involves the conversion of which two metabolites between the liver and muscles?

Lactate and glucose

In the fed state, which enzyme is activated to stimulate glycogen synthesis?

 

Glycogen synthase

Which of the following is a key difference in carbohydrate metabolism between feline and canine species?

 

Felines have a higher reliance on gluconeogenesis from proteins.

In general for monogastric animals, high levels of dietary ____________ fiber can increase the speed that food passes through the gastrointestinal tract.

Insoluble

In general for monogastric animals, dietary fiber is included in diets for all of the following reasons except...

 

Increase caloric density of the diet

Dogs with diabetes mellitus are predisposed to complications that occur throughout the body. These may include systemic, or whole body, inflammation, high fat in the blood, known as hyperlipidemia, and inflammation of the pancreas, or pancreatitis. Some research has demonstrated that this drug may help these dogs manage hyperlipidemia by influencing acetyl CoA carboxylase (ACC) activity indirectly. From what you know about ACC, which one of the following is false?

 

When ACC is active, it promotes fatty acid oxidation

True or false: The omega-3 fatty acid, known as linoleic acid, is an essential fatty acid.

False: it is an ALPHA-linoleic acid

both omega-3 and omega-6 are3 essential fatty acids

True or false: As part of the guaranteed analysis on a pet food label, the 'crude fiber' value includes all soluble and insoluble dietary fibers.

False

A middle-aged, overweight cat presents with anorexia, jaundice, and lethargy. Blood work reveals elevated liver enzymes and hyperbilirubinemia (elevation of bilirubin, a product of red blood cell breakdown). The veterinarian suspects hepatic lipidosis. Which of the following metabolic imbalances is most likely contributing to the development of hepatic lipidosis in this cat?

 

Increased mobilization of fatty acids from adipose tissue due to prolonged anorexia, overwhelming the liver's capacity to metabolize them.

A patient with poorly controlled type 1 diabetes is admitted with diabetic ketoacidosis (DKA). Which of the following best describes the most likely source and fate of acetyl-CoA in this condition?

 

oxidation of long chain fatty acids, β-hydroxybutyrate synthesis

A cat presents with muscle wasting, poor coat quality, and lethargy. Bloodwork shows low serum taurine levels. Given that taurine is an essential amino acid for felines (due to limited biosynthetic capacity to synthesize taurine from cysteine and methionine), indicate from the list below all of the amino acids that are considered nutritionally essential for cats?

• Lysine, an essential amino acid necessary for protein synthesis and energy metabolism.

• Threonine, an essential amino acid involved in gut mucin production and overall protein balance.

• Leucine, an essential amino acid that stimulates muscle protein synthesis, regulates blood sugar levels, and aids in tissue regeneration.

A dog with chronic kidney disease (CKD) is on a low-protein diet to minimize nitrogenous waste. Which one of the following statements is false with respect to the quality of the protein in this diet?

 

The low-protein diet should only include non-essential amino acids.

A cat is diagnosed with pancreatitis. In this condition, the cat experiences severe abdominal pain and elevated levels of free fatty acids in the blood. Which of the following processes is likely responsible for the increased levels of free fatty acids in this cat?

 

Increased lipolysis (i.e., tryglyceride catbolism) due to activation of adipose triglyceride lipase, hormone sensitive lipase and monoglyceride lipase.

What is the renal threshold for glucose in dogs and cats?

Dogs: about 180 mg/dL

Cats: about 240 mg/dL

True or false: Diabetes mellitus is caused by feeding larger amount of carbohydrates

False, can exacerbate but not cause

What percent of a monogastrics ME requirement comes from carbohydrates?

60%

What is dietary fiber?

Nondigestible CHO and lignin that are intact and intrinsic in plants

What are the primary components of dietary fiber?

Cellulose, lignin, hemicellulose, pectins, gums, mucilages

Chemical definition of dietary fiber

the sum of all non-starch polysaccharides (NSP), non-digestible oligosaccharides and lignin

Physiological definition of dietary fiber

all plant polysaccharides and lignin that are resistant to hydrolysis by endogenous secretions of the gastrointestinal tract

AAFCO definition of dietary fiber (canine/feline nutrition)

the portion of the edible parts of plants or analogous carbohydrates that are resistant to digestion and absorption in the small intestine of animals

consists of:

• polysaccharides

• oligosaccharides

• lignin

• associated plant substances that may be partially or completely fermented in the large intestine

B(1-4) glycosidic linkages

linkages of cellulose that are resistant to endogenous enzymes

a(1-4) glycosidic linkages

linkages of starch that are digested by endogenous enzymes

Define starch

primarily a storage carbohydrate; NOT DIETARY FIBER, concentration varies widely in animal feed ingredients; High starch foods = rice corn

Resistant starch

white beans, lentils, plantains; not fully digested in SI, is grouped within total dietary fiber and can provide health benefits similar to those of soluble fiber

Define oligosaccharides

found in plant cell calls, plasma membrane, vacuoles, etc. of beans, lentils, whole grains; non-digestible by mammalian enzymes; fructooligosaccharides = prebiotics

Define cell wall (insoluble fibers)

Cellulose: structural homopolysaccharide; glucose units linked together by β-1,4-glycosidic bonds, resistant to mammalian enzymes; partially fermentable in large bowel

Hemicellulose: structural heteropolysaccharide, resistant to mammalian enzymes; partially fermentable in large bowel

Define lignin (least fermentable)

complex structural, organic polymer; resistant to mammalian enzymes; non-fermentable by bacterial species; present in all vascular plants; Considered the greatest impediment to digestion

Define Phenolics

Present in many plants; defensive mechanism of plants; antinutritive

properties; antioxidant activity (e.g., wheat bran —> ferulic acid)

What is a draw back of doing a crude fiber analysis?

Underestimates dietary fiber by 30 to 60%

• does not represent soluble fiber

• lab-to-lab variation & method reporting

• contaminated with ash and NPN

• overestimate insoluble fiber in many co-products

Why do we utilize a total dietary fiber analysis?

more thorough and specific

• gives indication of all soluble + insoluble fiber types

• today the most accurate and encompassing fiber assay

• represents both soluble and insoluble

What are some drawbacks of total dietary fiber analysis?

• expensive

• time-consuming & labor intensive

• low throughput

• several methods, vary from lab to lab

True or false: soluble and insoluble dietary fiber can impact glucose absorption?

True

What are the components of soluble dietary fibers?

pectins, gums, mucilages, beta-glucans, some hemicelluloses

What are the components of insoluble dietary fibers?

cellulose, some hemicellulose, lignin

What are the effects of feeding soluble dietary fiber?

• increased water holding capacity (hydrophilic)

• delay gastric emptying, slows intestinal transit time, and delays glucose uptake (slows things down)

• modifies microbiome

• tends to be fermentable/rate of fermentability varies

• delays glucose uptake

What are the effects of feeding insoluble dietary fiber?

• decreased water holding capacity (hydrophobic)

• increased fecal bulk (more)

• faster transit time

• decrease transit time (speed things up)

  • impedes glucose absorption, hydrolysis of starch

• decreases energy density of diet, increases post-prandial satiety

• decreased fermentability

What are the proposed modes of action of insoluble fiber on gut health?

• increase passage rate, decrease pathogen proliferation and adhesion

• may decrease E. coli and diarrhea incidence

• increase fecal bulk (regular bowel movements)

• enhance satiety (fullness)

• SCFA production in large intestine/colon (fermentation of insoluble fiber components)

What are some other effects of fiber?

• growth performance

• weight control

• glycemic index

• satiety

How does fiber effect growth performance?

• Dietary fiber reduces energy intake via nutrient dilution (in excess it can have negative effects)

• small quantities of DF may improve growth performance but depends on type (source), animal species (age), and environment

  • if energy increases, fiber should decrease

How does fiber effect weight control?

• insoluble/soluble DF used to restrict nutrient digestion/absorption, energy intake

• fiber dilutes caloric content

  • possible mechanisms: regulation of appetite, mechanical interference, complex hormonal control

How does fiber effect glycemic index?

• Viscous fibers in SI act as a barrier to release of nutrients and slow absorption

  • overall effect is to control glucose/insulin metabolism

How does fiber effect satiety?

• gastric distention

• work/time for chewing

• hormonal (effect on leptin-hunger inhibitor vs ghrelin-hunger stimulator)

Lipids

soluble in organic solvents, and may serve as an energy source, a constituent of cell and organelle membranes, fat-soluble vitamins, corticosteroid hormones, and as mediators of electron transport (Coenzyme Q)

• triacylglycerols are most significant groups of lipids from energy metabolism standpoint

Where is insulin produced in the body?

Beta cells in the pancreas

True or false: Type 2 diabetes is reversible?

True

What dog breed(s) are predisposed to hypertriglyceridemia?

miniature schnauzers and beagls

What blood test can help diagnose diabetes mellitus?

All of the above

True or false: All insulin is dosed once a day?

False

What dietary component can slow gastric emptying and delay carbohydrate absorption?

soluble fiber

Diabetes mellitus is an endocrine disorder that occurs in both cats and dogs and describes an alteration in cellular transport and metabolism of glucose. It is NOT caused by which of the following?

Elevated levels of carbohydrate carbohydrate in the diet

True or false: soluble fiber is viscous?

True

Which of the following describes a saturated fatty acid?

no double bonds

in a fasted state what are lipids mainly used as?

energy source

True or false: fatty acid synthesis is down regulated in both the fasted state and when fed a high fat diet.

False

Fatty acid synthesis is UP-regulated in the presence of what hormone(s)?

upregulated in high energy state, when there is more insulin and build up of citrate (allosteric feedback)

True or false: fatty acid synthesis is down regulated in both the fasted state and when fed a high fat diet

True or false: Omega-3 fatty acids have anti-inflammatory properties

True

Which of the following are fates of amino acids in the fed state?

C. both A. and B.

The purpose of the Alanine cycle is to do which of the following, EXCEPT?

remove lactate from circulation

True or false: Aminotransferases catalyze oxidative deamination

False

True or false: aminotransferases catalyze oxidative deamination?

False

True or false: taurine is NOT used directly for muscle synthesis in cats?

True: important in diets but no directly for muscle synthesis

What happens to the albumin to globulin ratio in protein-losing enteropathies?

Stays the same

What are some causes of an elevated BUN in a dog?

GI bleeding, protein losing enteropathy, & increased protein catabolism

True or false: in the fasted state, there is net protein degredation in the body?

True

What does crude fiber analysis capture?

cellulose, lignin, and some hemicellulose

What does total dietary fiber analysis capture?

cellulose, lignin, hemicellulose, pectins & gums, beta-glucans, resistant starch, & non-digestible oligosaccharides

What is the significant of Acetyl CoA carboxylase (ACC) in de novo fatty acid synthesis?

It is the enzyme for the 1st (rate limiting step), carboxylation of acetyl CoA—> malonyl CoA

• it is under tight short-term control

How is Acetyl CoA carboxylase (ACC) down-regulated?

• as palmitoyl CoA (endproduct regulation) increases then ACC decreases

• phosphorylation of the enzyme (through a glucagon-cAMP cascade)

How is Acetyl CoA carboxylase (ACC) up-regulated?

• build up of citrate (allosteric)

• dephopshorylation of the enzyme (influenced by insulin/glucagon ratio)

alpha-linolenic acid

Omega-3

Linoleic acid

Omega-6

What is TAG catabolism?

break down of stored Triacylglycerols into free fatty acids and glycerol, initiates a cascade leading to the mobilization of individual fatty acids

Simple lipids

Fatty acids (FA)

• mono-, di-, and tri-acylglycerides (MAG, DAG, TAG)

Compound lipids

constitute a major class of lipids (e.g., phospholipids)

• phospholipids

• glycolipids

• lipoproteins

Derived lipids

obtained from simple or compound lipids that still possess the property of lipids (e.g., steroids)

Structure and function of fatty acids

FAs are important in energy metabolism and their length in foods ranges from 4 to 24 carbons

• may be saturated, monosaturated, and polyunsaturated

Delta fatty acid notation system

start carbon #/direction on carboxyl end (-COOH)

# carbons:#bonds with ^location of double bonds

Omega fatty acid notation system

start on methyl end (C—C)

#carbons:#bonds-first double bond only

Fatty acids that are typically most important nutritionally and functionally are __ or more carbons in length

14

Palmitic acids (16:0), stearic acid (18:0), oleic acid (18:1), and linoleic acid (18:2) together account for __% of of the fatty acids in the american diet

>90

what effects do a fat deficient diet lead to?

delayed growth, dermatitis, kidney lesions, and early death.

• it can be corrected by providing the essential fatty acid linoleic (18:2) and linoleic acids (18:3n-3)

Functions of lipids

• supply metabolic energy by oxidation of FA to CO2

• structural component of cell membranes (phospholipids/sphingolipids)

Less important but functionally significant:

• lubricants (e.g., complex lipids for maintenance of lung alveolar integrity)

• signaling molecules: regulatory roles in metabolism (examples: eicosanoids, cortisol, phosphatidylinositols)

FA synthase (FAS)

Second, and final committed step in FA synthesis

• FA synthesis from acetyl-CoA and malonyl-CoA

• FAS catalyzes series of reactions

  • very large polypeptide that includes an acyl carrier protein (ACP)

  • ACP: carrier or acyl intermediates during fatty acid synthesis

FAS control in fasted and fed states

Fasted: low FAS

Fed: increases drastically in fed state

What product is released from FAS?

Palmitate (16:0)

Where does FA elongation occur?

in Er and/or Mito, predominate site is ER membranes (FA desaturation occurs here as well)

In mammalian cells involves __ fatty acyl desaturase enzymes

4, designated at delta^9,6,5, and 4 fatty acyl-CoA desaturase.

Mammals cannot desaturate past delta 9; plants can

What are some roles of fatty acids?

• components of immune system (eicosanoids contribute to the inflammatory response)

• provide structural basis of cell membranes

• act as signaling molecules

• provide major energy substrates

What are the biological effects of eicosanoids, and what do they consist of?

Consist of the prostaglandins (PG), thromboxanes (TX), leukotrienes (LT), and lipoxins (LX)

• inflammatory responses

• effect intensity and duration of pain and fever

• reproductive function

• play important roles in inhibiting gastric acid secretion, regulating blood pressure through vasodilation or constriction, and inhibiting or activating platelet aggregation and thrombosis